bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the extent of therapy with prostate cancer in those receiving testosterone therapy in a US commercial insurance claims database
Authors: Lopez David S. , Huang Danmeng , Tsilidis Konstantinos K. , Khera Mohit , Williams Stephen B. , Urban Randall J. , Panagiotou Orestis A. , Kuo Yong‐fang , Baillargeon Jacques , Farias Albert , Krause Trudy
Published: September 2019

Background

Conflicting evidence remains in the association of testosterone therapy (TTh) with prostate cancer (PCa). This inconsistency maybe due, in part, to the small sample sizes from previous studies and an incomplete assessment of comorbidities, particularly diabetes.

Objective

We investigated the association of PCa with TTh (injection or gel) and different TTh doses and determined whether this association varies by the presence of diabetes at baseline in a large, nationally representative, commercially insured cohort.

Design

We conducted a retrospective cohort study of 189 491 men aged 40‐60 years old in the IBM MarketScan® Commercial Database, which included 1424 PCa cases diagnosed from 2011 to 2014. TTh was defined using CPT codes from inpatient and outpatient, and NDC codes from pharmacy claims. Multivariable adjusted Cox proportional hazards models were used to compute hazard ratios for patients with incident PCa.

Results

We found a 33% reduced association of PCa after comparing the highest category (>12) of TTh injections with the lowest (1‐2 injections) category (HR = 0.67, 95% CI: 0.54‐0.82). Similar statistical significant inverse association for PCa was observed for men who received TTh topical gels (>330 vs 1‐ to 60‐days supply). Among nondiabetics, we found significant inverse association between TTh (injection and gel) and PCa, but a weak interaction between TTh injections and diabetes (P = .05).

Conclusion

Overall, increased use of TTh is inversely associated with PCa and this remained significant only among nondiabetics. These findings warrant further investigation in large randomized placebo‐controlled trials to infer any health benefit by TTh.
Feasibility study comparing underwater endoscopic mucosal resection and conventional endoscopic mucosal resection for superficial non‐ampullary duodenal epithelial tumor < 20 mm
Authors: Kiguchi Yoshiyuki , Kato Motohiko , Nakayama Atsushi , Sasaki Motoki , Mizutani Mari , Tsutsumi Koushiro , Akimoto Teppei , Takatori Yusaku , Mutaguchi Makoto , Takabayashi Kaoru , Ochiai Yasutoshi , Maehata Tadateru , Kanai Takanori , Yahagi Naohisa
Published: September 2019

Background and Aim

Underwater endoscopic mucosal resection (UEMR) has been reported as an alternative to conventional EMR for superficial non‐ampullary duodenal epithelial tumors (SNADET). However, the detailed outcomes are unclear. This study aimed to compare the clinical outcomes between UEMR and EMR for SNADET <20 mm.

Patients and methods

This is a retrospective observational study using a prospective maintained database. From November 2017 to December 2018, 104 consecutive cases of attempted UEMR for SNADET <20 mm were prospectively allocated. A total of 240 cases of attempted EMR were chosen as historical controls. We compared technical success rate, defined as the resection rate without conversion to ESD; en bloc resection rate; R0 resection rate; and adverse event rate. Next, multivariate analyses were constructed to identify predictors of conversion to ESD, piecemeal resection, and RX or R1 (RX/R1) resection.

Results

Technical success rate of UEMR was significantly higher than that of EMR (87% and 70%, P < 0.01). En bloc resection and R0 resection rates of UEMR were significantly lower than those of EMR (en bloc resection: 87% vs 96%, P < 0.01; R0 resection: 67% vs 80%, P = 0.05). Concerning adverse events, there were no significant differences. In multivariate analyses, attempted EMR, lesion size and depressed type were independent predictors of conversion to ESD. Attempted UEMR was an independent predictor of piecemeal resection and RX/R1 resection.

Conclusion

The present study indicated that UEMR could be a feasible endoscopic resection method for SNADET (UMIN000025442).
Caesarean section and risk of type 1 diabetes: whole‐of‐population study
Authors: Begum M. , Pilkington R. , Chittleborough C. , Lynch J. , Penno M. , Smithers L.
Published: September 2019

Aim

A hypothesized mechanism for increased type 1 diabetes risk among caesarean births is lack of exposure to the vaginal microbiota. Children born by prelabour caesarean are not exposed to the vaginal microbiota, whereas caesarean births during labour (intrapartum) may be exposed. The aim of this study was to estimate type 1 diabetes risk among children born by caesarean compared with normal vaginal delivery.

Methods

This whole‐of‐population study linked routinely collected, de‐identified administrative data from the South Australian Early Childhood Data Project for all births from 1999 to 2013. Type 1 diabetes cases were identified using inpatient hospitalizations from 2001 to 2014 (ICD‐10‐AM codes E10‐E109). Type 1 diabetes risk for caesarean was assessed by Cox regression using two models: (i) caesarean vs. vaginal and (ii) prelabour or intrapartum caesarean vs. vaginal. Analyses were adjusted for confounding and multiple imputation was used to address missing data.

Results

A total of 286 058 children born between 1999 and 2013 contributed to 2 200 252 person‐years, of which 557 had type 1 diabetes. Of all births, 90 546 (31.7%) were caesarean, and of these 53.1% were prelabour and 46.9% intrapartum caesarean. Compared with vaginal delivery, the adjusted hazard ratio for type 1 diabetes was 1.05 [95% confidence interval (CI) 0.86–1.28) for caesarean, 1.02 (95% CI 0.79–1.32) for prelabour caesarean and 1.08 (95% CI 0.82–1.41) for intrapartum caesarean.

Conclusion

There may be a small increased type 1 diabetes risk following caesarean, but confidence intervals included the null. The lower estimate for prelabour compared with intrapartum caesarean, and the potential for unmeasured confounding suggest that neonatal vaginal microbiota might not be involved in type 1 diabetes.
VOLUNTARY DISCLOSURE AND EARNINGS EXPECTATIONS IN MULTI‐LEVEL MARKETING
Authors: Bosley Stacie A. , Greenman Sarah , Snyder Samantha
Published: September 2019

Multi‐level marketing (MLM) firms recruit individuals into a business opportunity but are not required to disclose the earnings of past participants. Some MLMs voluntarily create income disclosures, which may serve both marketing and risk‐management functions. We create an economic experiment to explore the impact of MLM income disclosure on consumer interest and expectations. Results suggest that disclosure does not significantly alter interest in the business opportunity but does reduce expectations, on average, when subjects are asked to estimate annual income in a lab environment. We discuss findings in the context of current regulatory policy. (JEL D18, D82, M38)
Identification of Colletotrichum species associated with anthracnose of Spondias spp. in Brazil
Authors: Carvalho Auricelia Sousa , Melo Maruzanete Pereira , Silva Juliana Pereira , Matos Kedma Silva , Beserra José Evando Aguiar
Published: September 2019

Plants of the genus Spondias are commonly cultivated in northern and north‐eastern Brazil for fruit production. Severe leaf anthracnose, caused by Colletotrichum spp., is frequently observed in several species of Spondias. The objectives of this study were to identify and characterize Colletotrichum species associated with anthracnose in species of Spondias by using the concept of morphological and phylogenetic analyses. Leaves with symptoms of anthracnose were collected from orchards in the state of Piauí, Brazil. Morphological identification; sequencing analysis of ACT, ITS and GS gene regions; and a pathogenicity test confirmed three Colletotrichum spp. (C. dianesei, C. siamense and C. brevisporum) were able to cause the disease. This is the first record of these species of Colletotrichum causing anthracnose in Spondias spp. in Brazil.
Growth of Phlebiopsis gigantea in wood of seven conifer species
Authors: Zaluma Astra , Bruna Lauma , Klavina Darta , Burnevica Natalija , Kenigsvalde Kristine , Lazdins Andis , Gaitnieks Talis
Published: September 2019

Heterobasidion parviporum and Heterobasidion annosum are widely distributed root‐rot fungi that infect conifers throughout Europe. Infection of conifer stumps by spores of these pathogens can be controlled by treating fresh stumps with a competing non‐pathogenic fungus, Phlebiopsis gigantea. In this study, growth of three Latvian strains of P. gigantea and the biological control agent ‘Rotstop’ strain was evaluated in stem pieces of Norway spruce, Scots pine, lodgepole pine, Douglas‐fir, Weymouth pine, Siberian larch and Sitka spruce. The growth rates of one H. parviporum and one H. annosum isolate were also measured in the same stem pieces. The growth rate of P. gigantea varied greatly in wood of different conifer species. It was higher in the three pine species, lower in Norway spruce and lowest in Sitka spruce and Siberian larch, and in Douglas‐fir, this fungus did not grow. The largest area of wood occupied by P. gigantea was in lodgepole pine. Growth of Latvian isolates of P. gigantea in the wood of Pinus and Picea species was comparable to that of the Rotstop isolate. Consequently, stump treatment with local P. gigantea isolates should be recommended. However, our results suggest that Douglas‐fir stump treatment against Heterobasidion by P. gigantea may be ineffective and other stump treatment methods should be considered.
Brain responses and approach bias to social alcohol cues and their association with drinking in a social setting in young adult males
Authors: Groefsema Martine M. , Mies Gabry W. , Cousijn Janna , Engels Rutger C. M. E. , Sescousse Guillaume , Luijten Maartje
Published: September 2019

Alcohol is mainly consumed in social settings, in which people often adapt their drinking behaviour to that of others, also called imitation of drinking. Yet, it remains unclear what drives this drinking in a social setting. In this study, we expected to see stronger brain and behavioural responses to social compared to non‐social alcohol cues, and these responses to be associated with drinking in a social setting. The sample consisted of 153 beer‐drinking males, aged 18–25 years. Brain responses to social alcohol cues were measured during an alcohol cue‐exposure task performed in an fMRI scanner. Behavioural responses to social alcohol cues were measured using a stimulus‐response compatibility task, providing an index of approach bias towards these cues. Drinking in a social setting was measured in a laboratory mimicking a bar environment. Specific brain responses to social alcohol cues were observed in the bilateral superior temporal sulcus and the left inferior parietal lobe. There was no approach bias towards social alcohol cues specifically; however, we did find an approach bias towards alcohol (versus soda) cues in general. Brain responses and approach bias towards social alcohol cues were unrelated and not associated with actual drinking. Thus, we found no support for a relation between drinking in a social setting on the one hand, and brain cue‐reactivity or behavioural approach biases to social alcohol cues on the other hand. This suggests that, in contrast to our hypothesis, drinking in a social setting may not be driven by brain or behavioural responses to social alcohol cues.
Conceived Through Rape/Incest? Adoptive Parents’ Experiences Managing Uncertainty and Disclosure Surrounding their Children's Origins
Authors: Goldberg Abbie E. , Manley Melissa H. , Frost Reihonna L. , McCormick Nora M.
Published: September 2019

Adoptive parents may be placed with children conceived under difficult circumstances, such as via rape or incest. At the same time, adoptive parents are generally encouraged to communicate openly with their children about their adoption stories and birth families. No research has examined the experiences of parents who adopt children who were conceived through rape or incest. This exploratory study examines how parents discuss their decision‐making when adopting children conceived via rape or incest, how they manage varying levels of uncertainty about their children's origins, and whether and how they plan to disclose this information to children. The researchers used thematic analysis to examine the experiences of 11 couples (22 parents) interviewed at four time points after adopting children who were reportedly conceived via rape or incest. Findings revealed that even soon after adopting, parents discussed the need to eventually talk to their children about their conception circumstances. Parents generally struggled to determine how and when to disclose this information, particularly when they felt uncertain about the veracity of the conception stories they had been told. Some hoped to rely on professionals or birth mothers to guide them in these communications. Findings have implications for supporting adoptive families as they navigate the complexity of managing sensitive information and uncertainty when adopting children conceived through rape or incest. Practitioners should provide ongoing guidance to adoptive parents about how and when to disclose developmentally appropriate information to children about difficult conception circumstances.
Microbial metabolite fluxes in a model marine anoxic ecosystem
Authors: Louca Stilianos , Astor Yrene M. , Doebeli Michael , Taylor Gordon T. , Scranton Mary I.
Published: September 2019

Permanently anoxic regions in the ocean are widespread and exhibit unique microbial metabolic activity exerting substantial influence on global elemental cycles and climate. Reconstructing microbial metabolic activity rates in these regions has been challenging, due to the technical difficulty of direct rate measurements. In Cariaco Basin, which is the largest permanently anoxic marine basin and an important model system for geobiology, long‐term monitoring has yielded time series for the concentrations of biologically important compounds; however, the underlying metabolite fluxes remain poorly quantified. Here, we present a computational approach for reconstructing vertical fluxes and in situ net production/consumption rates from chemical concentration data, based on a 1‐dimensional time‐dependent diffusive transport model that includes adaptive penalization of overfitting. We use this approach to estimate spatiotemporally resolved fluxes of oxygen, nitrate, hydrogen sulfide, ammonium, methane, and phosphate within the sub‐euphotic Cariaco Basin water column (depths 150–900 m, years 2001–2014) and to identify hotspots of microbial chemolithotrophic activity. Predictions of the fitted models are in excellent agreement with the data and substantially expand our knowledge of the geobiology in Cariaco Basin. In particular, we find that the diffusivity, and consequently fluxes of major reductants such as hydrogen sulfide, and methane, is about two orders of magnitude greater than previously estimated, thus resolving a long‐standing apparent conundrum between electron donor fluxes and measured dark carbon assimilation rates.
Testing for changes in biomass dynamics in large‐scale forest datasets
Authors: Rutishauser Ervan , Wright Stuart J. , Condit Richard , Hubbell Stephen P. , Davies Stuart J. , Muller‐Landau Helene C.
Published: September 2019

Tropical forest responses to climate and atmospheric change are critical to the future of the global carbon budget. Recent studies have reported increases in estimated above‐ground biomass (EAGB) stocks, productivity, and mortality in old‐growth tropical forests. These increases could reflect a shift in forest functioning due to global change and/or long‐lasting recovery from past disturbance. We introduce a novel approach to disentangle the relative contributions of these mechanisms by decomposing changes in whole‐plot biomass fluxes into contributions from changes in the distribution of gap‐successional stages and changes in fluxes for a given stage. Using 30 years of forest dynamic data at Barro Colorado Island, Panama, we investigated temporal variation in EAGB fluxes as a function of initial EAGB (EAGBi) in 10 × 10 m quadrats. Productivity and mortality fluxes both increased strongly with initial quadrat EAGB. The distribution of EAGB (and thus EAGBi) across quadrats hardly varied over 30 years (and seven censuses). EAGB fluxes as a function of EAGBi varied largely and significantly among census intervals, with notably higher productivity in 1985–1990 associated with recovery from the 1982–1983 El Niño event. Variation in whole‐plot fluxes among census intervals was explained overwhelmingly by variation in fluxes as a function of EAGBi, with essentially no contribution from changes in EAGBi distributions. The high observed temporal variation in productivity and mortality suggests that this forest is very sensitive to climate variability. There was no consistent long‐term trend in productivity, mortality, or biomass in this forest over 30 years, although the temporal variability in productivity and mortality was so strong that it could well mask a substantial trend. Accurate prediction of future tropical forest carbon budgets will require accounting for disturbance‐recovery dynamics and understanding temporal variability in productivity and mortality.
Prognosis Following Discontinuation of OnabotulinumA Therapy in “Super‐responding” Chronic Migraine Patients
Authors: Ching Jason , Tinsley Amanda , Rothrock John
Published: September 2019

Objective

To determine whether the successful treatment of chronic migraine (CM) with onabotulinumA (BotoxA) may be followed by a continued respite from headache once therapy has been discontinued.

Background

The optimal duration of prophylactic therapy for migraine generally and for CM treated with BotoxA specifically is unknown.

Methods

We conducted a prospective cohort study evaluating a series of patients with CM at a university‐affiliated headache subspecialty clinic in Reno, Nevada, all of whom were treated according to a uniform protocol involving serial injections of BotoxA. We followed all positively responding patients who met our stopping rule for a minimum of 6 months after discontinuation of BotoxA, and we assessed the incidence of clinical worsening in that group.

Results

A total of 105/131 patients (80%) for whom complete follow‐up was available reported no clinical worsening or need to resume prophylactic therapy over the 6 months following discontinuation of BotoxA therapy. Patients with pre‐treatment baseline chronic daily headache (CDH) of greater than 6 months duration were more likely to report clinical deterioration within 6 months of stopping treatment, as compared to patients with CDH of less than 6 months. A greater number of BotoxA treatments required to achieve our stopping rule correlated with clinical deterioration within 6 months of stopping treatment.

Conclusions

In many CM patients who experience an especially positive response to serial BotoxA injection therapy, clinical improvement may be sustained for a period of at least 6 months following discontinuation of prophylactic therapy.
The effects of ball milling time on the rheological, optical, and microstructural properties of YAG transparent ceramics
Authors: Mohammadi Fatemeh , Mirzaee Omid , Tajally Mohammad
Published: September 2019

Stable slurries dispersed mixture of commercial Al2O3 and Y2O3 powders, ammonium poly meta acrylate (Dolapix CE64) as the dispersant, and tetraethyl orthosilicate (TEOS) as the sintering aid were prepared by ball milling process. The effects of the milling time on the fabrication of transparent polycrystalline yttrium aluminum garnet (YAG) ceramics were investigated by slip casting and vacuum sintering. The results showed that the best milling time for the deagglomeration of the powder mixture was 16 hours and the slurry prepared during this time showed a near‐Newtonian behavior due to the better deagglomeration and lower viscosity. X‐ray patterns also showed that all samples were pure YAG phase. The results also revealed that the sample prepared by 16 hours ball milling time suspensions exhibited higher relative green and final density, as well as the maximum transmittance at 1064 nm (≈ 77%). These samples had a more uniform microstructure too.
Life cycle assessment of a ceramic glaze containing copper slags and its application on ceramic tile
Authors: Mohaddes Khorassani Sara , Siligardi Cristina , Mugoni Consuelo , Pini Martina , Cappucci Grazia Maria , Ferrari Anna Maria
Published: September 2019

Even though copper slags have many possible applications, their disposal is still practiced, creating long‐term waste management problems. This led to the investigation of new products for residential applications, taking advantages of the interesting chemical properties of copper slag. This study aims to assess the environmental impact of the use of copper slag as secondary raw material in a ceramic glaze composition and to compare it with a traditional glaze. A manufacturing process was designed, through an industrial scale up operation from experimental laboratory data and the entire life cycle of the products was analyzed using the Life‐cycle assessment (LCA) methodology. Considering the production of a ceramic glaze containing copper slag, the most impacting process resulted the one related to frit production, due to the large amount of thermal energy necessary for the raw materials melting. The comparative LCA analysis carried out between the frit obtained from metallurgical slags and a traditional one, demonstrated that the innovative ceramic frit has a greater environmental advantage. The LCA analysis allowed to highlight the most impactful stages of an industrial process using copper slag as a secondary raw material for glaze production and to quantify the potential environmental advantages of this operation.
Subjective well‐being and valuation of future health states: Discrepancies between anticipated and experienced life satisfaction
Authors: Walasek Lukasz , Brown Gordon D. A. , Ovens Gordon D.
Published: September 2019

One way of informing health policy decisions is to ask people about the impact that different health states would have on their future subjective well‐being. The present research explored the relation between anticipated and experienced changes in health‐related subjective well‐being, and examined whether affective forecasting errors could be reduced by psychological distancing manipulations. Using survey methodology, we tested whether people can accurately estimate the impact of different possible health states on their subjective well‐being. We also manipulated psychological distance: Forecasts were made about present self, future self, or others. Based on construal level theory and past work on affective forecasting errors, our prediction was that increasing psychological distance may reduce the mismatch between anticipated and experienced impact of health states on subjective well‐being. We found that the impact of ill health on subjective well‐being was greatly overpredicted and that this overprediction was not eliminated when participants were asked to make predictions about themselves in the future or about other people. Consistent with past work, we found that our participants correctly expected that their subjective well‐being would deteriorate more if they experienced the highest levels of mental illness as compared to the highest intensities of pain or most severe limitations to physical functioning.
Reconstructing the geographic and climatic origins of long‐distance bird migrations
Authors: Dufour Paul , Descamps Sébastien , Chantepie Stéphane , Renaud Julien , Guéguen Maya , Schiffers Katja , Thuiller Wilfried , Lavergne Sébastien
Published: September 2019

Aim

Seasonal bird migration is one of the most fascinating global ecological phenomena. Yet, the biogeographic scenarios and climatic drivers that led single species or entire lineages to evolve seasonal migration between disjunct breeding and wintering ranges remain unclear. Based on distribution and phylogenetic data for all birds worldwide, we explored the biogeographic and climatic context of the evolutionary emergence of seasonal geographic migration in birds.

Location

Global.

Taxon

The Aves class (9,819 species).

Methods

We used the worldwide phylogeny of all birds, with a new backbone tree, to test the link between birds’ migration distance (short, variable, long) and strategy (resident, mixed, strict migrant) with four different metrics depicting species’ thermal niches in their breeding and wintering ranges. We also performed ancestral state reconstructions for the main migratory orders to reconstruct past events of appearance and loss of migration behaviour, and past biogeographic scenarios that led to the emergence of seasonal geographic migration.

Results

Migratory species generally experience warmer climates in their wintering range compared to their breeding one, although notable exceptions exist. This thermal niche change due to migration was found to be much larger for species travelling large distances. We also found that geographic migration emerged at different time periods through varied biogeographic paths (i.e. both from temperate and tropical ancestors) and that migration behaviour was likely ancestral to Passeriformes, with several subsequent episodes of loss of migration behaviour.

Main conclusions

We report an evolutionary correlation between long‐distance migration and the tendency of birds to seek warmer climates during their non‐breeding period, compared to short‐distance migrants. Migration behaviour was likely ancestral to Passeriformes, and migratory lineages in general seem to have often adapted to novel ecological opportunities by returning to a resident state. Our results provide the first large‐scale study of biogeographic and climatic origins of bird migration worldwide.
Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice
Authors: Zhang Wenzhe , Li Li , Zheng Yu , Xue Fei , Yu Mengzhu , Ma Yongbin , Dong Liyang , Shan Zirui , Feng Dingqi , Wang Ting , Wang Xuefeng
Published: September 2019

Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthma. We previously identified SJMHE1, a small molecule peptide from the HSP60 protein of Schistosoma japonicum. SJMHE1 can inhibit delayed‐type hypersensitivity and collagen‐induced arthritis in mice. In the present study, we evaluated this peptide's potential intervention effect and mechanism on ovalbumin‐induced asthma in mice. SJMHE1 treatment suppressed airway inflammation in allergic mice, decreased the infiltrating inflammatory cells in the lungs and bronchoalveolar lavage fluid, modulated the production of pro‐inflammatory and anti‐inflammatory cytokines in the splenocytes and lungs of allergic mice, reduced the percentage of Th2 cells and increased the proportion of Th1 and regulatory T cells (Tregs). At the same time, Foxp3 and T‐bet expression increased, and GATA3 and RORγt decreased in the lungs of allergic mice. We proved that SJMHE1 can interrupt the development of asthma by diminishing airway inflammation in mice. The down‐regulation of Th2 response and the up‐regulation of Th1 and Tregs response may contribute to the protection induced by SJMHE1 in allergic mice. SJMHE1 can serve as a novel therapy for asthma and other allergic or inflammatory diseases.
Integrating Multiple Sources of Validity Evidence for an Assessment‐Based Cognitive Model
Authors: Langenfeld Thomas , Thomas Jay , Zhu Rongchun , Morris Carrie A.
Published: September 2019

An assessment of graphic literacy was developed by articulating and subsequently validating a skills‐based cognitive model intended to substantiate the plausibility of score interpretations. Model validation involved use of multiple sources of evidence derived from large‐scale field testing and cognitive labs studies. Data from large‐scale field testing were evaluated using traditional psychometric methods. The psychometric analyses were augmented using eye tracking technology to perform gaze pattern and pupillometry analyses to gain better understanding of problem‐solving strategies and cognitive load. Findings from the data sources were integrated to provide strong evidence supporting the model and score interpretations. Implications for using gaze pattern and pupillometry analyses to enhance learning and assessment are discussed.
Logistic Regression Procedure Using Penalized Maximum Likelihood Estimation for Differential Item Functioning
Authors: Lee Sunbok
Published: September 2019

In the logistic regression (LR) procedure for differential item functioning (DIF), the parameters of LR have often been estimated using maximum likelihood (ML) estimation. However, ML estimation suffers from the finite‐sample bias. Furthermore, ML estimation for LR can be substantially biased in the presence of rare event data. The bias of ML estimation due to small samples and rare event data can degrade the performance of the LR procedure, especially when testing the DIF of difficult items in small samples. Penalized ML (PML) estimation was originally developed to reduce the finite‐sample bias of conventional ML estimation and also was known to reduce the bias in the estimation of LR for the rare events data. The goal of this study is to compare the performances of the LR procedures based on the ML and PML estimation in terms of the statistical power and Type I error. In a simulation study, Swaminathan and Rogers's Wald test based on PML estimation (PSR) showed the highest statistical power in most of the simulation conditions, and LRT based on conventional PML estimation (PLRT) showed the most robust and stable Type I error. The discussion about the trade‐off between bias and variance is presented in the discussion section.
Disease burden of Crigler–Najjar syndrome: Systematic review and future perspectives
Authors: Dhawan Anil , Lawlor Michael W , Mazariegos George V , McKiernan Patrick , Squires James E , Strauss Kevin A , Gupta Digant , James Emma , Prasad Suyash
Published: September 2019

Background and Aim

Crigler–Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5′‐diphosphate glucuronyltransferase activity leading to unconjugated hyperbilirubinemia and its attendant risk for irreversible neurological injury (kernicterus). CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients.

Methods

A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS.

Results

Twenty‐eight articles on clinical aspects of CNS were identified, but no published data on its humanistic or economic burden were found. In patients with complete UGT1A1 deficiency (type 1 CNS [CNS‐I]), unconjugated bilirubin levels increase 3–6 mg/dL/day during the newborn period and reach neurologically dangerous levels between 5 and 14 days of age. Phototherapy is the mainstay of treatment but poses significant challenges to patients and their families. Despite consistent phototherapy, patients with CNS‐I have worsening hyperbilirubinemia with advancing age. Liver transplantation is the only definitive therapy for CNS‐I and is increasingly associated with excellent long‐term survival but also incurs high costs, medical and surgical morbidities, and risks of immunosuppression.

Conclusions

Crigler–Najjar syndrome is associated with a substantial burden, even with existing standards of care. The development of novel disease‐modifying therapies has the potential to reduce disease burden and improve the lives of CNS patients and their families.
Resilience in Clinical Care: Getting a Grip on the Recovery Potential of Older Adults
Authors: Gijzel Sanne M. W. , Whitson Heather E. , van de Leemput Ingrid A. , Scheffer Marten , van Asselt Dieneke , Rector Jerrald L. , Olde Rikkert Marcel G. M. , Melis René J. F.
Published: September 2019

Background

Geriatricians are often confronted with unexpected health outcomes in older adults with complex multimorbidity. Aging researchers have recently called for a focus on physical resilience as a new approach to explaining such outcomes. Physical resilience, defined as the ability to resist functional decline or recover health following a stressor, is an emerging construct.

Methods

Based on an outline of the state‐of‐the‐art in research on the measurement of physical resilience, this article describes what tests to predict resilience can already be used in clinical practice and which innovations are to be expected soon.

Results

An older adult's recovery potential is currently predicted by static tests of physiological reserves. Although geriatric medicine typically adopts a multidisciplinary view of the patient and implicitly performs resilience management to a certain extent, clinical management of older adults can benefit from explicitly applying the dynamical concept of resilience. Two crucial leads for advancing our capacity to measure and manage the resilience of individual patients are advocated: first, performing multiple repeated measurements around a stressor can provide insight about the patient's dynamic responses to stressors; and, second, linking psychological and physiological subsystems, as proposed by network studies on resilience, can provide insight into dynamic interactions involved in a resilient response.

Conclusion

A big challenge still lies ahead in translating the dynamical concept of resilience into clinical tools and guidelines. As a first step in bridging this gap, this article outlines what opportunities clinicians and researchers can already exploit to improve prediction, understanding, and management of resilience of older adults. J Am Geriatr Soc 67:2650–2657, 2019
A comparative study on auditory and hyoid bones of Jurassic euharamiyidans and contrasting evidence for mammalian middle ear evolution
Authors: Meng Jin , Mao Fangyuan , Han Gang , Zheng Xiao‐Ting , Wang Xiao‐Li , Wang Yuanqing
Published: September 2019

The holotypes of euharamiyidan Arboroharamiya allinhopsoni and Arboroharamiya jenkinsi preserve the auditory and hyoid bones, respectively. With additional structures revealed by micro‐computerized tomography (CT) and X‐ray micro‐computed laminography (CL), we provide a detailed description of these minuscule bones. The stapes in the two species of Arboroharamiya are similar in having a strong process for insertion of the stapedius muscle. The incus is similar in having an almond‐shaped body and a slim short process, in addition to a robust stapedial process with a short lenticular process preserved in A. allinhopsoni. The plate‐like ectotympanic in the two species of Arboroharamiya is similar and comparable to that of Qishou jizantang. The surangular in the two species has a fan‐shaped body and a needle‐shaped anterior process. The malleus, ectotympanic, and surangular are fully detached from the dentary and should have functioned exclusively for hearing. All the auditory bones of Arboroharamiya display unique features unknown in other mammaliaforms. Moreover, hyoid elements are found in the two species of Arboroharamiya and co‐exist with the five auditory bones in the holotype of A. allinhopsoni. The element interpreted as the stylohyal is similar to the bone identified as the ectotympanic in Vilevolodon. We reconstruct the auditory apparatus of Arboroharamiya and compare it with that of Vilevolodon as well as those in extant mammals and basal mammaliaforms. The comparison shows diverse morphological patterns of the auditory region in mammaliaforms. In particular, those of Vilevolodon and Arboroharamiya differ significantly: the former has a mandibular middle ear, whereas the latter possesses a definitive mammalian middle ear. It is puzzling that the two sympatric and dentally similar taxa have such different auditory apparatuses. In light of the available evidence, we argue that the mandibular middle ear reconstructed in Vilevolodon encounters many problems, and the so‐called ectotympanic in Vilevolodon may be interpreted as a stylohyal; thus, the dilemma can be resolved.
Novel solute carrier family 26, member 3 mutation in a prenatal recurrent case with congenital chloride diarrhea
Authors: Wu Siqi , Han Jin , Zhang Yongling , Ye Zhichao , Lu Ping , Tian Kege
Published: September 2019

Congenital chloride diarrhea (CCD) is an autosomal recessive hereditary disease manifested by persistent, watery, profuse diarrhea with high chloride concentration (>90 mmol/L). Postnatally, neonates suffer from hypochloremia, hyponatremia, hypokalemia, metabolic alkalosis, dehydration, developmental retardation, or even death. Prenatal diagnosis is of great importance for the prognosis of CCD. We report a prenatal recurrent case of CCD. Prenatal ultrasound revealed fetal diffuse intestinal dilation with the typical honeycomb sign and polyhydramnios with high amniotic fluid index. The whole exome capture and massively‐parallel DNA sequencing showed an abnormal mutation of Solute Carrier Family 26, Member 3 (SLC26A3), c.1039G>A (p.Ala347Thr), and the mutation sites were verified by sanger sequencing. When prenatal ultrasound shows polyhydramnios and diffuse intestinal dilation, CCD should be suspected. Molecular genetic testing can be helpful for the diagnosis.
Effects of Lactobacillus plantarum on the intestinal morphology, intestinal barrier function and microbiota composition of suckling piglets
Authors: Wang Qi , Sun Qian , Qi Renli , Wang Jing , Qiu Xiaoyu , Liu Zuohua , Huang Jinxiu
Published: September 2019

This study investigated the effect of Lactobacillus plantarum strain 299v on gut health in suckling piglets. Sixty newborn piglets were assigned to control and probiotic treatments, with three litters per treatment (ten piglets/litter). From days 1 to 20 of life, piglets were orally administered a placebo of 0.1% peptone or 1.0 ×  1010 CFU L. plantarum 299v daily. Six piglets per treatment were sacrificed on day 20, and intestinal tissues (including duodenum, jejunum, ileum and colon) and the intestinal contents from colon segments were collected. The results demonstrated that piglets treated with L. plantarum 299v had a lower diarrhoea incidence than the controls. L. plantarum 299v administration significantly increased the ratio of the villus height to the crypt depth in the jejunum and ileum, as well as the mRNA expression of jejunal occludin and ileal zonula occludens 1 (ZO‐1). The L. plantarum treatment also increased the mRNA abundance of porcine β‐defensin 2 (pBD2) and pBD3 in the jejunum and ileum and of toll‐like receptors (TLRs), such as TLR2, TLR4, TLR6 and TLR9 in the ileum, and significantly upregulated the mRNA abundances of ileal pBD1 and colonic TLR4. Additionally, the L. plantarum 299v treatment significantly changed the structure of the colonic microbiota, as evidenced by the obvious increases in the relative abundances of the phyla Firmicutes and Actinobacteria and of the genus Lactobacillus. Our findings indicate that L. plantarum 299v facilitates the gut health of suckling piglets, probably by improving the intestinal morphology and intestinal barrier function and by modifying the structure of the gut microbiota.
Effects of glucagon‐like peptides 1 and 2 and epidermal growth factor on the epithelial barrier of the rumen of adult sheep
Authors: Greco Gabriele , Amasheh Salah , Shen Zanming , Lu Zhongyan , Aschenbach Jörg R.
Published: September 2019

Epidermal growth factor (EGF) and glucagon‐like peptides (GLP) modulate the tight junctions (TJ) of the intestinal epithelial barrier (EB) of monogastric animals. This work tried to elucidate whether GLP‐1, GLP‐2 and EGF can affect the EB of the rumen. Ovine ruminal epithelia were incubated in Ussing chambers for 7 hr with 25 or 250 nM of either GLP‐1 or GLP‐2 on the serosal side, with 2.5 nM of EGF on the serosal side or with 0.25 or 2.5 nM EGF on the mucosal side. No treatment affected tissue conductance. Short‐circuit current (Isc) was affected by time and treatment and their interactions. Only 250 nM of either GLP‐1 or GLP‐2 decreased Isc in certain periods compared with 25 nM GLP‐1 or 0.25 nM mucosally applied EGF; however, not when compared to control epithelia. Fluorescein flux rates (Jfluor) of ruminal epithelia were affected by treatment, time and time × treatment interaction. The time × treatment interaction was based on an increase in Jfluor between the first and last hour in epithelia incubated with 25 nM GLP‐1 or GLP‐2 and in epithelia incubated with EGF. After 7 hr incubation, claudin‐7 mRNA expression was downregulated in all treatments. Claudin‐1 mRNA was upregulated after incubation with 2.5 nM EGF on the serosal side, claudin‐4 mRNA was downregulated by 2.5 nM EGF on the mucosal side, and occludin mRNA was increased after incubation with 250 nM GLP‐2. The protein abundance of all tested TJ proteins was not influenced by treatment. We conclude that GLP‐1, GLP‐2, and EGF have no obvious acute effects on the EB of ruminal epithelia under simulated physiological conditions ex vivo. However, by decreasing the mRNA expression of claudin‐7 and partly affecting other TJ proteins, they may modulate EB in the longer term or under certain conditions.
Extracting Conditionally Heteroskedastic Components using Independent Component Analysis
Authors: Miettinen Jari , Matilainen Markus , Nordhausen Klaus , Taskinen Sara
Published: September 2019

In the independent component model, the multivariate data are assumed to be a mixture of mutually independent latent components. The independent component analysis (ICA) then aims at estimating these latent components. In this article, we study an ICA method which combines the use of linear and quadratic autocorrelations to enable efficient estimation of various kinds of stationary time series. Statistical properties of the estimator are studied by finding its limiting distribution under general conditions, and the asymptotic variances are derived in the case of ARMA‐GARCH model. We use the asymptotic results and a finite sample simulation study to compare different choices of a weight coefficient. As it is often of interest to identify all those components which exhibit stochastic volatility features we suggest a test statistic for this problem. We also show that a slightly modified version of the principal volatility component analysis can be seen as an ICA method. Finally, we apply the estimators in analysing a data set which consists of time series of exchange rates of seven currencies to US dollar. Supporting information including proofs of the theorems is available online.
Impacts of phenological variability in a predatory larval salamander on pond food webs
Authors: Anderson T. L. , Stemp K. M. , Ousterhout B. H. , Burton D. , Davenport J. M.
Published: September 2019

Phenological shifts are expected to affect species interactions, in part by influencing which size classes, life stages or species occur simultaneously in a community. Yet, changes in phenology beyond shifts to the first, mean or median date of an ontogenetic event are underexplored in their importance to community dynamics. Using outdoor mesocosms, we experimentally mimicked increasing variability in breeding phenology of a top predatory salamander in pond food webs (Ambystoma annulatum) to assess its impacts on its own demographic traits and survival. We also tested whether variability in predator breeding would cascade to impact survival and diversity of lower trophic levels (intermediate salamander predators, anuran tadpoles, zooplankton and periphyton). We found that only variability in body size at metamorphosis of A. annulatum was impacted by phenological manipulations, with size variability being greater at higher levels of phenological variability. Because size at metamorphosis is often correlated with adult fitness, covarying variability in body size and phenology may lead to altered population dynamics. We also found that the density and size of A. annulatum were better predictors of overall survival and diversity of amphibian prey compared to phenological variability. We speculate that overwintering mortality of A. annulatum due to pond freezing modulated the impacts of phenological variability, such that changes in demographic traits and cascading effects throughout the food web were mollified.
A European ECMM‐ESCMID survey on goals and practices for mycobiota characterisation using next‐generation sequencing
Authors: Gangneux Jean‐Pierre , Guegan Hélène , Vandenborght Louise‐Eva , Buffet‐Bataillon Sylvie , Enaud Raphael , Delhaes Laurence
Published: September 2019

Although substantial efforts have been made to investigate about the composition of the microbiota, fungi that constitute the mycobiota play a pivotal role in maintaining microbial communities and physiological processes in the body. Here, we conducted an international survey focusing on laboratory's current procedures regarding their goals and practices of mycobiota characterisation using NGS. A questionnaire was proposed to laboratories affiliated to working groups from ECMM (NGS study group) and ESCMID (ESGHAMI and EFISG study groups). Twenty‐six questionnaires from 18 countries were received. The use of NGS to characterise the mycobiota was not in routine for most of the laboratories (N = 23, 82%), and the main reason of using NGS was primary to understand the pathophysiology of a dysbiosis (N = 20), to contribute to a diagnosis (N = 16) or to implement a therapeutic strategy (N = 12). Other reported reasons were to evaluate the exposome (environmental studies) (N = 10) or to investigate epidemics (N = 8). Sputum is the main sample studied, and cystic fibrosis represents a major disease studied via the analysis of pulmonary microbiota. No consensus has emerged for the choice of the targets with 18S, ITS1 and ITS2 used alternatively among the laboratories. Other answers are detailed in the manuscript. We report a photography of mycobiota analysis that may become a major tool in the near future. We can draw some conclusions on the diversity of approaches within the answers of the 27 laboratories and underline the need for standardisation.
Neuropathological characterization of a novel TANK binding kinase (TBK1) gene loss of function mutation associated with amyotrophic lateral sclerosis
Authors: Weinreich M. , Shepheard S. R. , Verber N. , Wyles M. , Heath P. R. , Highley J. R. , Kirby J. , Shaw P. J.
Published: September 2019

Aims

Mutations in TANK binding kinase gene (TBK1) are causative in amyotrophic lateral sclerosis (ALS), however correlations between clinical features and TBK1 mutations have not been fully elucidated. We aimed to identify and compare TBK1 mutations to clinical features in a cohort of ALS patients from Northern England.

Methods

TBK1 mutations were analysed in 290 ALS cases. Immunohistochemistry was performed in brain and spinal cord of one case with a novel in‐frame deletion.

Results

Seven TBK1 variants were identified, including one novel in‐frame deletion (p.85delIle). In silico analysis and literature suggested four variants were pathogenic, and three were variants of uncertain significance or benign. Post‐mortem immunohistochemistry established an individual with the novel in‐frame deletion had classical ALS and Type B FTLD‐TDP pathology, with no changes in TBK1 staining or interferon regulatory factor IRF3.

Conclusions

TBK1 mutations were present in 1.38% of our cohort, and screening showed no clear genotype‐phenotype associations compared to other genetic and sporadic ALS cases. TBK1 immunohistochemistry was consistent with previously published literature and we are the first to show no differential expression of interferon regulatory factor IRF3, a downstream effector of TBK1 in the immune pathway, in the TBK1‐mutant tissue, compared to controls.