bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term changes in the gut microbiota after 14‐day bismuth quadruple therapy in penicillin‐allergic children
Authors: Zhou Ying , Ye Ziqing , Lu Junping , Miao Shijian , Lu Xiaolan , Sun Hua , Wu Jie , Wang Yuhuan , Huang Ying
Published: July 2020

Background

Penicillin‐allergic children who are infected with Helicobacter pylori constitute a relatively common subgroup. We aimed to study the short‐term and long‐term effects of bismuth quadruple therapy on gut microbiota in penicillin‐allergic children.

Methods

We prospectively recruited treatment‐naive children with H pylori infection and H pylori‐negative asymptomatic children as healthy controls. Patients received 14‐day bismuth quadruple therapy consisting of omeprazole, clarithromycin, metronidazole, and bismuth. Fecal samples were collected at weeks 0, 2, 6, and 52. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing.

Results

Twenty‐two subjects (14 gastritis patients, 8 duodenal ulcer patients) and 23 controls participated in this study. At week 2, alpha diversity was reduced in both gastritis (P < .05) and ulcer (except P = .16 with Chao 1 index) patients compared with baseline. Some changes persisted at week 6, and all were restored at week 52. Beta diversity was significantly altered 2 weeks after treatment in the gastritis and duodenal ulcer groups (P = .001, P = .002, respectively) and restored at weeks 6 and 52. The mean relative abundance of Bacteroidetes (P < .001, P = .005, respectively) decreased and that of Proteobacteria increased (P < .001, P = .03, respectively). All alterations recovered at week 6 and 52. In both the gastritis and ulcer groups at week 2, some beneficial bacteria were decreased including Bacteroides (P < .001 and P = .003), Faecalibacterium (P < .001 and P = .02), Phascolarctobacterium (P = .002 and P = .004), Roseburia ( P < .001 and P = .13), Bifidobacterium (P = .08 and P = .04), and Blautia (P < .001 and P = .002). Some detrimental bacteria were increased including Escherichia‐Shigella (P < .001 and P = .19), Klebsiella (P < .001, and P = .09), Enterococcus (P < .001 and P = .007), and Streptococcus (P = .002 and P = .004). The changes returned to almost the pre‐eradication level 1 year after therapy.

Conclusion

Bismuth quadruple therapy causes short‐term dysbiosis of the gut microbiota. Most changes recovered 1‐year post‐eradication, indicating the long‐term safety of H pylori therapy.
Bismuth quadruple regimen with tetracycline or doxycycline versus three‐in‐one single capsule as third‐line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp‐EuReg)
Authors: Nyssen Olga P. , Perez‐Aisa Angeles , Rodrigo Luis , Castro Manuel , Mata Romero Pilar , Ortuño Juan , Barrio Jesus , Huguet Jose Maria , Modollel Ines , Alcaide Noelia , Lucendo Alfredo , Calvet Xavier , Perona Monica , Gomez Barbara , Gomez Rodriguez Blas Jose , Varela Pilar , Jimenez‐Moreno Manuel , Dominguez‐Cajal Manuel , Pozzati Liliana , Burgos‐Santamaria Diego , Bujanda Luis , Hinojosa Jenifer , Molina‐Infante Javier , Di Maira Tommaso , Ferrer Luis , Fernández‐Salazar Luis , Figuerola Ariadna , Tito Llucia , de la Coba Cristobal , Gomez‐Camarero Judith , Fernandez Nuria , Caldas Maria , Garre Ana , Resina Elena , Puig Ignasi , O’Morain Colm , Megraud Francis , Gisbert Javier P.
Published: July 2020

Background

Different bismuth quadruple therapies containing proton‐pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third‐line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin.

Aim

To evaluate the efficacy and safety of third‐line treatments with bismuth, metronidazole, and either tetracycline or doxycycline.

Methods

Sub‐study with Spanish data of the “European Registry on H pylori Management” (Hp‐EuReg), international multicenter prospective non‐interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin‐ and levofloxacin‐containing therapies, patients receiving a third‐line regimen with 10/14‐day bismuth salts, metronidazole, and either tetracycline (BQT‐Tet) or doxycycline (BQT‐Dox), or single capsule (BQT‐three‐in‐one) were included. Data were registered at AEG‐REDCap database. Univariate and multivariate analyses were performed.

Results

Four‐hundred and fifty‐four patients have been treated so far: 85 with BQT‐Tet, 94 with BQT‐Dox, and 275 with BQT‐three‐in‐one. Average age was 53 years, 68% were women. Overall modified intention‐to‐treat and per‐protocol eradication rates were 81% (BQT‐Dox: 65%, BQT‐Tet: 76%, BQT‐three‐in‐one: 88%) and 82% (BQT‐Dox: 66%, BQT‐Tet: 77%, BQT‐three‐in‐one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01‐8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15‐3.33); BQT‐three‐in‐one was superior to BQT‐Dox (OR = 4.46; 95% CI = 2.51‐8.27), and BQT‐Tet was marginally superior to BQT‐Dox (OR = 1.67; 95% CI = 0.85‐3.29).

Conclusion

Third‐line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10‐day BQT‐three‐in‐one or 14‐day BQT‐Tet. Doxycycline seems to be less effective and therefore should not be recommended.
Has Oppy Done Away with the Aristotelian Proof?
Authors: McNabb Tyler , DeVito Michael
Published: July 2020

In this essay, we engage with Graham Oppy’s work on Thomas Aquinas’s First Way. We argue that Oppy’s objections shouldn’t be seen as successful. In order to establish this thesis, we first analyze Oppy’s exegesis of Aquinas’s First Way, as well as the counter‐arguments he puts forth (including the charge that Aquinas’s argument is invalid or, if deemed valid, forces one to adopt determinism). Next, we address Oppy’s handling of the contemporary scholarship covering the First Way. Specifically, we lay out Edward Feser’s most recent formulation of the argument and analyze Oppy’s main objection to it.
Sulfur and carbon isotopic systematics of Guadalupian‐Lopingian (Permian) mid‐Panthalassa: δ34S and δ13C profiles in accreted paleo‐atoll carbonates in Japan
Authors: Maruoka Teruyuki , Isozaki Yukio
Published: July 2020

Immediately before the extinction of the end‐Guadalupian (Middle Permian; ca 260 Ma), a significant change to the global carbon cycle occurred in the superocean Panthalassa, as indicated by a prominent positive δ13C excursion called the Kamura event. However, the causes of this event and its connection to the major extinction of marine invertebrates remain unclear. To understand the mutual relationships between these changes, we analyzed the sulfur isotope ratio of the carbonate‐associated sulfate (CAS) and HCl‐insoluble residue, as well as the carbon isotope ratio of bulk organic matter, for the Middle‐Upper Permian carbonates of an accreted mid‐oceanic paleo‐atoll complex from Japan, where the Kamura event was first documented. We detected the following unique aspects of the stable carbon and sulfur isotope records. First, the extremely high δ13C values of carbonate (δ13Ccarb) over +5 ‰ during the Capitanian (late Guadalupian) were associated with large isotopic differences between carbonate and organic matter (Δ13C = δ13Ccarb − δ13Corg). We infer that the Capitanian Kamura event reflected an unusually large amount of dissolved organic matter in the expanded oxygen minimum zone at mid‐depth. Second, the δ34S values of CAS (δ34SCAS) were inversely correlated with the δ13Ccarb values during the Capitanian to early Wuchiapingian (early Late Permian) interval. The Capitanian trend may have appeared under increased oceanic sulfate conditions, which were accelerated by intense volcanic outgassing. Bacterial sulfate reduction with increased sulfate concentrations in seawater may have stimulated the production of pyrite that may have incorporated iron in pre‐existing iron hydroxide/oxide. This stimulated phosphorus release, which enhanced organic matter production and resulted in high δ13Ccarb. Low δ34SCAS values under high sulfate concentrations were maintained and the continuous supply of sulfate cannot by explained only by the volcanic eruption of the Emeishan Trap, which has been proposed as a cause of the extinction. The Wuchiapingian δ34SCAS–δ13Ccarb correlation, likely related to low sulfate concentration, may have been caused by the removal of oceanic sulfate through the massive evaporite deposition.
Effect of the plant waste onto the properties of use and the microstructure of phyllosilicates based ceramics
Authors: Serewane Deramne Rosellyne , Lecomte‐Nana Gisèle Laure , Peyratout Claire , Naït‐Ali Benoit , Tchangbedji Gado
Published: July 2020

The present study aimed at using plant waste (Musa Paradisiaca) for manufacturing clay‐based ceramics in order to promote lower sintering temperature while preserving the properties of use. Two kaolinic‐illitic clays (NZ1 and KO) from Central African Republic were used mixed with 1 to 10 mass% of the plant waste (MP). The clays and the waste exhibited accessory phases: quartz and iron oxides, and K2O respectively. MP was collected, dried and sieved (<100 μm) previously to its mixture with clays. According to the sintering behavior of KO and NZ1 derived from thermodilatometry, the densification was obtained after firing at 1200°C. Results showed that open porosity decreased from 35% to 17% with increasing temperature in the range 900 to 1200°C for KO and NZ1. This porosity remained in the range 30%‐40% while increasing the MP content (firing at 1000°C for 1h.). The optimized MP content was 3 and 5 mass% for KO and NZ1 clay materials respectively. The compressive strength and thermal conductivities were improved compared to clay samples without MP fired at 1200°C. Moreover a significant decrease in the sintering temperature was achieved, leading to energy saving in line with sustainability issues.
Repeat serological testing for anti‐citrullinated peptide antibody after commencement of therapy is not helpful in patients with seronegative rheumatoid arthritis
Authors: Reid Alistair B. , Wiese Michael , McWilliams Leah , Metcalf Rob , Hall Cindy , Lee Anita , Hill Catherine , Wechalekar Mihir , Cleland Les , Proudman Susanna M.
Published: July 2020

Background

Anti‐citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) define ‘seropositive’ rheumatoid arthritis (RA). Both predict unfavourable disease course, development of extra‐articular features and treatment outcomes. We investigated the prevalence of seroconversion to ACPA after commencement of triple disease‐modifying anti‐rheumatic drug (DMARD) treat‐to‐target therapy.

Aim

To Investigate the prevalence of seroconversion to ACPA after commencement of triple DMARD treat‐to‐target therapy.

Methods

DMARD‐naïve patients with RA according to the 1987 American College of Rheumatology criteria and disease duration of <96 weeks were enrolled. RF and ACPA levels were recorded at baseline and sequentially during triple DMARD therapy.

Results

A total of 368 patients was followed for a median of 272 weeks. Of 154 patients seronegative for ACPA at recruitment, 10 (6.5%) seroconverted at some point. Nine of these were positive for RF at baseline and baseline RF titre was predictive of seroconversion. Four (2.6%) patients remained seropositive. No patients seroconverted from negative to positive for both RF and ACPA. Median time to seroconversion for ACPA was 29 months.

Conclusion

Persistent seroconversion of ACPA from negative to positive after diagnosis in patients with RA is uncommon. ACPA and RF double negative patients are highly unlikely ever to develop ACPA positivity with a risk <1%. It is therefore unlikely to be helpful or cost‐effective to perform serial ACPA measurements in patients with seronegative RA after commencement of a treat‐to‐target strategy.
Left anterior descending artery dissection: a rare sequela of blunt chest trauma
Authors: Das Souvik K. , Itty Charles , Vaishnav Manan , Mumford Drew
Published: July 2020

Traumatic coronary artery (CA) dissection is an extremely rare sequela of blunt chest trauma. Diagnosis of CA dissection in the setting of chest trauma is challenging. While conventionally coronary angiography has been the diagnostic tool of choice, modern imaging techniques such as optical coherence tomography can further improve diagnostic accuracy and help optimise treatment strategy. The ideal treatment modality for managing CA dissection has not been established with case reports revealing a range of treatment strategies ranging from CA bypass grafting to a completely conservative management. Here we present a case report of a 68‐year‐old man who suffered a traumatic proximal left anterior descending artery dissection as a consequence of a motor‐vehicle accident and was subsequently treated with a combination of conservative and interventional strategy with optimal patient outcome.
Patients with multiple myeloma over a large catchment of 2.5 million square kilometres: a Western Australia retrospective survival review
Authors: Ng Teng Fong , Burrow Sally , Leahy Michael , Augustson Bradley , Trentino Kevin , De Kraa Rebecca , Wright Matthew , Carnley Ben
Published: July 2020

Multiple myeloma is an incurable malignancy of plasma cells. We retrospectively reviewed the survival outcomes of patients with multiple myeloma in Western Australia (WA) public hospitals over a 10‐year period. We did not detect a difference in survival between patients residing in the metropolitan Perth and regional areas, despite a paucity of haematology services in regional WA due to low population density in a large geographic area. Patients with revised international staging system Stage 3 had the poorest survival in our cohort with median survival of 24 months.
Diabetes insipidus complicating apoplexy during pregnancy: the potential use of copeptin
Authors: Bichard Lisa K. , Torpy David J.
Published: July 2020

Pituitary apoplexy during pregnancy is rare but important to recognise, particularly in the hyperoestrogenaemic state when known lactotroph hyperplasia occurs. Untreated, the complication rates from pituitary adenomas depend on the size of the adenoma before pregnancy. A history of thirst plus polydipsia during pregnancy raises suspicion for diabetes insipidus and a 24‐h urine collection quantifying polyuria with an inappropriately low urine osmolality confirms the diagnosis. Further evaluation for assessing diabetes insipidus in pregnancy may be facilitated by the use of a copeptin.
Maternal origins, population structure and demographic history of ten Chinese indigenous goat breeds from Yunnan
Authors: Li Rong , Sun Jianshu , Zhao Yincheng , Xiao Heng , Chen Shanyuan
Published: July 2020

Yunnan as a frontier zone that connects China with South and Southeast Asia, has 11 well‐recognized goat breeds. However, the knowledge about maternal origins, population structure and demographic history of Chinese indigenous goats from Yunnan is limited. In this study, we analysed a 481‐bp fragment of first hypervariable segment (HVSI) of the mitochondrial DNA (mtDNA) control region sequences of 749 individuals from 10 Yunnan indigenous goat breeds, of which 556 sequences were newly determined. There were 110 polymorphic sites that defined 158 haplotypes among all sequences. The haplotype and nucleotide diversity of these breeds ranged from 0.782 ± 0.079 to 0.982 ± 0.015 and from 0.028 ± 0.003 to 0.043 ± 0.005, respectively. Phylogenetic analysis identified two lineages A and B, of which the lineage A had higher frequency (68.1%) and distributed in all Yunnan breeds. We combined previously reported sequences with our sequences belonging to the lineage B and detected two subclades B1 and B2, in which the B1 subclade shared individuals from Eastern Asia, Southeast Asia and Southern Asia. Given higher level of diversity and more unique haplotypes, the B2 subclade probably originated from Southwestern China. The haplotype network, analysis of molecular variance (AMOVA) and a Mantel test revealed no significant phylogeographic structuring among Yunnan goat breeds. This can be explained by high gene flow and genetic admixture among these breeds from different geographic regions in Yunnan. Additionally, both the lineages A and B reflected different demographic histories. This study will provide a scientific basis for the conservation and utilization of Yunnan indigenous goats.
Commentary: Implications for future research on the genetic and environmental causes of callous–unemotional traits – a commentary on Takahashi et al (2020)
Authors: Frick Paul J.
Published: July 2020

Takahashi et al. (2020) showed that CU traits at age 7 were highly heritable, that the genetic influences underlying the course of CU traits from age 7 to 16 were largely independent from those underlying the initial level, and that the genetic influences on CU traits in early childhood were substantially different from the genetic influences on these traits in adolescence. This commentary on these important and provocative findings focuses on their implications for future research. Specifically, it notes that future studies attempting to find genetic loci related to CU traits need to consider that such loci may differ depending on the age of the sample and this research needs to consider several important considerations when measuring CU traits that can influence the results. Further, the results of Takahashi et al highlight the importance of environmental influences on the stability of CU traits that could play an important role in treatment.
The importance of skin manifestations, serology and nailfold (video)capillaroscopy in morphea and systemic sclerosis: current understanding and new insights
Authors: Mostmans Y. , Richert B. , Badot V. , Nagant C. , Smith V. , Michel O.
Published: July 2020

Since the field around morphea and systemic sclerosis (SSc) is evolving rapidly, this review approaches conventional as well as more recent clinical developments from a dermatological point of view. Skin manifestations are critical in sub‐classifying these diseases ensuring a correct prognosis for these patients. They can be discretely present, and therefore, diagnosis can be challenging sometimes, implicating a thorough dermatological examination is mandatory. Furthermore, a growing amount of dermatologists perform nailfold videocapillaroscopy (NVC), a more recent reliable non‐invasive imaging technique used for in vivo assessment of the microcirculation at the nailfold. After all, specific NVC‐changes are present in a majority of patients with SSc. This way, dermatologists not only take part in the diagnosis process through clinical investigation but also through the use of a modern state of the art imaging technique that is becoming the golden standard in SSc multidisciplinary workup. In this review, current understandings for NVC in morphea and SSc are revised. So far, the role of NVC in the diagnosis/prognosis/classification of morphea patients has not been thoroughly investigated to make proper conclusions. As for SSc, it is well known that NVC contributes to the diagnosis and can make a fundamental difference especially when obvious clinical SSc signs are absent. This review emphasizes the (somewhat underestimated) role of dermatologists in the process of diagnosis and follow‐up, and thus, the difference we can make for our patients and fellow colleagues in the multidisciplinary workup of SSc and morphea.
Work Schedule Unpredictability: Daily Occurrence and Effects on Working Parents' Well‐Being
Authors: Ananat Elizabeth O. , Gassman‐Pines Anna
Published: July 2020

Objective

To investigate the pervasiveness and frequency of work schedule unpredictability among workers in low‐wage hourly jobs and the effects of work schedule unpredictability on worker and family well‐being.

Background

Family science has long considered the ways in which parents' experiences in the workplace can affect families. Although unpredictability in work schedules has increased over time, especially for low‐wage workers, the effects of schedule unpredictability on worker and family well‐being have been understudied.

Method

Ninety‐two workers with children aged 2–7, recruited using a new venue‐time sampling technique, were asked to complete once‐a‐day surveys for 30 consecutive days (N = 2,221 person‐days for analysis). Descriptive analyses and regression models with family fixed effects were utilized.

Results

Work schedule unpredictability was common in the context of families' lives: over the 30 days, parents experienced an unanticipated work schedule change on 13.3% of days, and 87% of parents experienced at least one unanticipated work schedule change. Within families, unpredictable work schedule changes on a given day were associated with worse outcomes that day for parents, including increased negative mood and decreased perceived sleep quality.

Conclusion

Work schedule unpredictability is ubiquitous in the lives of low‐wage hourly workers and is negatively related to working parents' well‐being.

Implications

These results provide evidence that unscheduled and canceled shifts typical of low‐wage service jobs may harm parents' well‐being, which could ultimately affect their children's development and well‐being.
Foundations of oral health‐related quality of life
Authors: John Mike T.
Published: July 2020

Oral health‐related quality of life (OHRQOL) is the component of health‐related quality of life that relates to the effects of oral diseases and dental interventions on patients. This article describes why OHRQOL is important and how it is measured. The conceptual basis for OHRQOL is discussed. A four‐dimensional structure consisting of Oral Function, Orofacial Pain, Orofacial Appearance and Psychosocial Impact as the OHRQOL dimensions has emerged as psychometrically sound and clinically intuitive. Consequently, when the impact of oral diseases or the effects of dental interventions are measured, four dimension scores capturing these attributes need to be used.
Prevalence and severity of periodontal disease in a historical Austrian population
Authors: Bertl Kristina , Tangl Stefan , Rybaczek Tina , Berger Barbara , Traindl‐Prohazka Martina , Schuller‐Götzburg Peter , Grossschmidt Karl
Published: July 2020

Objective

To assess the prevalence and severity of periodontitis based on different diagnostic methods in a historical Austrian population from the early middle ages.

Background

The description of the oral health status of archaeological material can provide interesting insights into prevalence, severity, and extent of oral diseases. Herein, the periodontal health status of the skeletal remains of medieval Avars (700‐800 AD), which were considered as one of the earliest Avarian settlements in Austria, was investigated.

Methods

The skeletal remains of 128 Avars were examined; age and gender were estimated by standard forensic methods and tooth loss and root caries were recorded. Periodontitis was assessed by (a) measurement of the alveolar bone levels (ABL) and (b) evaluation of the interdental septa.

Results

A mean ABL of 4.8 mm was determined, root caries tended to accumulate in teeth with a higher alveolar bone loss, and on average, 6.2 teeth were lost antemortem. Independent of the diagnostic method >90% of the subjects were judged as periodontally diseased, and age and tooth type were significant predictors. However, on the tooth level the presence of periodontitis varied considerably depending on the diagnostic method; that is, 7.6% versus 47.2% of the teeth were judged as healthy based on ABL or interdental septa, respectively.

Conclusion

The periodontal status of the skeletal remains of medieval Avars revealed a considerable high prevalence of periodontitis (ie, >90% of this population displayed periodontal tissue breakdown). However, the diagnostic method, disease definition, and data presentation should be considered when comparing results of archaeological material.
Analysis of polymorphisms of canine Cytochrome P 450‐CYP2D15
Authors: van Hagen Marjan A. E. , Schipper Louska , Oosterveer‐van der Doelen Marjolein A. M. , Vos‐Loohuis Manon , Gehring Ronette , Leegwater Peter A.
Published: July 2020

Cytochrome P450 (CYP) proteins constitute a large ancient family of oxidative enzymes essential for the efficient elimination of a wide variety of clinically used drugs. Polymorphic variants of human CYP2D6 are associated with the conversion rate and efficacy of several drugs such as antidepressants. Polymorphisms of the canine orthologue CYP2D15 are of interest because these antidepressants are also used in dogs with behavioral problems and the outcome of the treatment is variable. However, the annotated CYP2D15 gene is incomplete and inaccurately assembled in CanFam3.1, hampering DNA sequence analysis of the gene in individual dogs. We elucidated the complete exon–intron structure of CYP2D15 to enable comprehensive genotyping of the gene using genomic DNA. We surveyed variations of the gene in four diverse dog breeds and identified novel polymorphisms in exon 2 in border collies. Further investigation to establish the impact of these canine CYP2D15 polymorphisms on interindividual variability in expression and function of this metabolizing enzyme is now feasible. Further knowledge of CYP pharmacogenetics will help individualize therapy and thereby increase therapeutic efficacy, especially in the use of antidepressants in veterinary behavioral medicine.
Sebelipase alfa for lysosomal acid lipase deficiency: 5‐year treatment experience from a phase 2 open‐label extension study
Authors: Malinová Vĕra , Balwani Manisha , Sharma Reena , Arnoux Jean‐Baptiste , Kane John , Whitley Chester B. , Marulkar Sachin , Abel Florian
Published: July 2020

Background and Aims

Lysosomal acid lipase deficiency is characterized by hepatomegaly and dyslipidaemia, which can lead to cirrhosis and premature atherosclerosis. Sebelipase alfa is an approved recombinant human lysosomal acid lipase. In an open‐label extension study of adults with lysosomal acid lipase deficiency (LAL‐CL04), sebelipase alfa treatment for 1 year reduced serum transaminase levels and liver fat content and improved serum lipid levels.

Methods

Final data from LAL‐CL04 are reported herein for patients who received sebelipase alfa infusions (1.0 or 3.0 mg/kg every other week) for up to 5 years.

Results

Of 8 patients enrolled, 7 received sebelipase alfa for 224‐260 weeks; 1 was lost to follow‐up. Median baseline levels of alanine aminotransferase and aspartate aminotransferase (81.5 and 50.0 U/L, respectively) were decreased through the end‐of‐study visit (54.0 and 34.0 U/L). Median low‐density lipoprotein cholesterol decreased from 113 to 78 mg/dL, total cholesterol decreased from 171 to 132 mg/dL, and high‐density lipoprotein cholesterol increased from 37 to 42 mg/dL. Most treatment‐emergent adverse events were nonserious (99%), mild/moderate (98%) and unrelated to sebelipase alfa (87%); no patient discontinued as a result of treatment‐emergent adverse events. One patient had 2 serious treatment‐emergent adverse events (cholecystitis and cholelithiasis; assessed as unlikely related to sebelipase alfa). Two patients had 20 nonserious infusion‐associated reactions in weeks 6‐38; all were manageable. One patient tested positive for antidrug antibodies (single occurrence).

Conclusions

Sebelipase alfa was well tolerated and improved serum transaminase and lipid levels for up to 5 years in adults with lysosomal acid lipase deficiency.

Trial registration number: ClinicalTrials.gov record NCT01488097.
Overabundant wild ungulate populations in Europe: management with consideration of socio‐ecological consequences
Authors: Valente Ana M. , Acevedo Pelayo , Figueiredo Ana M. , Fonseca Carlos , Torres Rita T.
Published: July 2020

Throughout recent years, ungulates have experienced significant increases in numbers and geographic range sizes in Europe, becoming locally overabundant populations in some regions. Changes in legislation regarding poaching, abandonment of land and re‐naturalisation of habitats, and decreasing numbers of hunters, among other things, have led to alarming scenarios in wild ungulate biology. Although ungulates bring some financial benefits for ecosystems and society through tourism and hunting, the problems associated with populations that are no longer controlled can outweigh the advantages. Damage to forestry and agriculture, ungulate‐vehicle collisions, and diseases are among the most concerning problems related to ungulate overabundance.

To deal with these problems and to decide on the best management strategy to apply, it is essential to have tools available to monitor populations with an integrative approach based on ecological change indicators, and to assess population and ecosystem status. Furthermore, in a globalised world, people’s opinions matter, and sociological studies regarding human perception of wild mammals must take place in order to allow proper management, including consideration of people’s expectations as well as animal and ecosystem needs. Successful and unsuccessful management strategies have already been attempted, and the knowledge of consequences over time enables an adaptive approach.

Management of ungulate populations is a complex subject, and each case should be studied, analysing the cost_performance balance of measures to be taken, and ensuring ongoing financial means to carry out and continue with successful ecosystem management strategies. Multidisciplinary teams should be built, including biologists, veterinarians, stakeholders, sociologists, and others, to deal with the management of European wild ungulate populations.
Identifying mesopredator release in multi‐predator systems: a review of evidence from North America
Authors: Jachowski David S. , Butler Andrew , Eng Robin Y.Y. , Gigliotti Laura , Harris Stephen , Williams Amanda
Published: July 2020

The mesopredator release hypothesis, defined as the change in distribution, abundance or behaviour of a middle‐ranking predator in response to a decrease in density or distribution of an apex predator, is an increasingly popular topic in ecology. Terrestrial mesopredators have been reported as being released in multiple systems globally, particularly in North America, over the past century.

We reviewed 2687 scientific articles, of which we determined that 38 met our criteria for investigating mesopredator release (MR) in terrestrial North American mammalian predators.

We observed no support or mixed support for MR in 46% of all relevant studies, including conflicting evidence between measures (mesopredator distribution, abundance or behaviour) within a given study and among studies of the same community in different settings.

To advance the study of MR, we provide a conceptual framework that 1) highlights the multiple spatial, temporal and ecological scales at which mesopredator responses can occur; 2) suggests the relative weight of evidence for MR that is provided by measures of mesopredator responses at each scale; and 3) clearly defines the threshold for determining when MR is occurring.

In increasingly reshuffled predator communities with declining apex predators, there is a need for future studies to assess in more detail the contexts in which mesopredator behavioural responses scale up to the population‐level processes and species‐level distribution changes needed to identify these responses as MR.
Short, Heavy and Underrated? Teacher Assessment Biases by Children's Body Size
Authors: Black Nicole , de New Sonja C.
Published: July 2020

We compare non‐blind teacher assessments with blind national test scores in maths to examine teacher‐test score disparities by children's height and weight. Relative to test scores, shorter and heavier children are rated less favourably by teachers. This teacher‐test score discrepancy cannot be explained by the child's behaviours, motivation to learn or cognitive ability. Unobserved student fixed effects across subjects explain the teacher‐test score discrepancy by height, but not weight. Our analysis points to biased teacher assessments as the most plausible explanation for the remaining teacher‐test score gap by weight. We find harsher teacher assessments are associated with a reduction in both the child's future test performance and liking for maths 4 years later.
The updated JSPGHAN guidelines for the management ofHelicobacter pyloriinfection in childhood
Authors: Kato Seiichi , Shimizu Toshiaki , Toyoda Shigeru , Gold Benjamin D. , Ida Shinobu , Ishige Takashi , Fujimura Shigeru , Kamiya Shigeru , Konno Mutsuko , Kuwabara Kentaro , Ushijima Kosuke , Yoshimura Norikazu , Nakayama Yoshiko ,   the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition
Published: July 2020

The Japan PediatricHelicobacter pyloriStudy Group published the first guidelines on childhoodH. pyloriinfection in 1997. They were later revised by the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (JSPGHAN). TheH. pylorieradication rates, when employing triple therapy with amoxicillin and clarithromycin, currently recommended as the first‐line therapy ofH. pyloriinfection in Japan, have substantially decreased, creating an important clinical problem worldwide. In Japanese adults, the “test‐and‐treat” strategy forH. pyloriinfection is under consideration as an approach for gastric cancer prevention. However, the combined North American and European pediatric guidelines have rejected such a strategy for asymptomatic children. As risk for gastric cancer development is high in Japan, determining whether the “test‐and‐treat” strategy can be recommended in children has become an urgent matter. Accordingly, the JSPGHAN has produced a second revision of theH. pyloriguidelines, which includes discussion about the issues mentioned above. They consist of 19 clinical questions and 34 statements. AnH. pyloriculture from gastric biopsies is recommended, not only as a diagnostic test for active infection but for antimicrobial susceptibility testing to optimize eradication therapy. Based upon antimicrobial susceptibility testing ofH. pyloristrains (especially involving clarithromycin), an eradication regimen including use of the antibiotics to whichH. pyloriis susceptible is recommended as the first‐line therapy againstH. pylori‐associated diseases. The guidelines recommend against a “test‐and‐treat” strategy forH. pyloriinfection for asymptomatic children to protect against the development of gastric cancer because there has been no evidence supporting this strategy.
Drivers and Implications of Direct‐Store‐Delivery in Distribution Channels
Authors: Kurtuluş Mümin , Savaskan R. Canan , Wang Chunlin
Published: July 2020

Direct‐Store‐Delivery (DSD) is an arrangement in which a retailer allows a manufacturer to execute in‐store operations such as shelf replenishments. This paper studies the economic drivers and implications of DSD for retailers and manufacturers. We consider a distribution channel where two competing manufacturers sell their products via a shelf‐space constrained retailer. The shelf space allocated to each product affects the cost associated with in‐store operations. The retailer can offer DSD to neither, one, or both manufacturers. The manufacturers respond by accepting or rejecting the retailer’s DSD offer. After the channel arrangement is determined, the manufacturers set their wholesale prices and then the retailer sets retail prices. Our results suggest that DSD is adopted when (i) the operational cost associated with shelf replenishments is convex, and (ii) competition between the manufacturers is intense enough to ensure the retailer’s willingness to offer DSD, but not so intense to deter the manufacturers from adopting DSD. Furthermore, we find that DSD increases the wholesale prices, decreases the retail prices, and increases demand for each product. The implication of this finding is that DSD can benefit not only the involved retailer and manufacturer but also the consumers.
How Decision Complexity Affects Outcomes in Combinatorial Auctions
Authors: Adomavicius Gediminas , Curley Shawn P. , Gupta Alok , Sanyal Pallab
Published: July 2020

Procurement mechanisms used by businesses have evolved from simple single‐item auctions to complex multi‐unit, multi‐attribute, and multi‐object auctions and their combinations. These state‐of‐the‐art mechanisms offer many economic benefits but also introduce challenges such as the increased complexity in decision‐making for the participants. Our primary goal in this study is to study how decision complexity affects the economic outcomes and acceptability of an advanced economic mechanism: the continuous combinatorial auction. We identify three aspects of complexity—auction size, competition, and the number of active bids. We examine these complexity aspects with five types of auctions conducted with a general consumer population in an experimental environment with real payoffs. We find that various aspects of complexity affect economic outcomes in different ways. Furthermore, competition is a critical factor for conducting efficient auctions. We also conduct a secondary analysis of bidder behavior through a granular examination of clickstream data collected during the auctions. We find that decision complexity influences bidder strategies leading to differences in auction outcomes. Based on our analysis, we develop valuable insights for auction practitioners.
Maternal hypertensive disorders and subtypes of hypospadias: A Dutch case‐control study
Authors: Jamaladin Hussein , van Rooij Iris A. L. M. , van der Zanden Loes F. M. , van Gelder Marleen M. H. J. , Roeleveld Nel
Published: July 2020

Background

Hypospadias is a frequently occurring congenital anomaly in male infants, in which the opening of the urethra is located along the ventral side of the penis. Although various studies attempted to identify its causes, the aetiology of the majority of hypospadias cases remains poorly understood. Maternal hypertensive disorders are believed to be associated with hypospadias, but the results of previous studies are not consistent, especially for subtypes of hypospadias.

Objectives

To investigate the associations between maternal hypertensive disorders, stratified by pharmacological treatment, and the occurrence of hypospadias divided into subtypes in a large population‐based case‐control study.

Methods

We included 887 hypospadias cases and 1005 male controls from the AGORA data‐ and biobank. Cases and controls were born in the periods 1975‐2016 and 1990‐2011, respectively. All data were collected in the period 2004‐2018. Maternal questionnaires were used to obtain information on hypertensive disorders during pregnancy, antihypertensive medication treatment, and potential confounders. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the associations between hypertensive disorders and hypospadias were estimated using logistic regression.

Results

Hypertensive disorders were reported by 15.3% of the women in this study. Maternal hypertensive disorders in general, chronic hypertension, and gestational hypertension were not associated with hypospadias or its subtypes. Preeclampsia was associated with posterior hypospadias (aOR 3.09, 95% CI 1.49, 6.43), whether it was untreated (aOR 2.81, 95% CI 1.24, 6.38) or pharmacologically treated preeclampsia (aOR 4.96, 95% CI 1.08, 22.80).

Conclusions

Our findings indicate that preeclampsia is associated with posterior hypospadias, irrespective of pharmacological treatment. This result supports the hypothesis of aetiological heterogeneity among the subtypes of hypospadias, with pregnancy‐related risk factors being associated with the more severe types of hypospadias.
Progesterone modulates theta oscillations in the frontal‐parietal network
Authors: Riddle Justin , Ahn Sangtae , McPherson Trevor , Girdler Susan , Frohlich Flavio
Published: July 2020

The neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognition, yet, the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern, often related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. We measured the concentration of P4 and T using salivary enzyme immunoassay and FMT oscillations using high‐density electroencephalography (EEG) during eyes‐open resting‐state in 55 healthy women and men. Electrical brain activity was analyzed using Fourier analysis, aperiodic signal fitting, and beamformer source localization. Steroid hormone concentrations and biological sex were used as predictors for scalp and source‐estimated amplitude of theta oscillations. Elevated concentrations of P4 predicted increased amplitude of FMT oscillations across both sexes, and no relationship was found with T. The positive correlation with P4 was specific to the frontal midline electrodes and survived correction for the background aperiodic signal of the brain. Using source localization, FMT oscillations were localized to the frontal‐parietal network (FPN). Additionally, theta amplitude within the FPN, but not the default mode network, positively correlated with P4 concentration. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the FPN.
Endobronchial coils for emphysema: Do they work and why?
Authors: Kotecha Sakhee , Williams Trevor J.
Published: July 2020

See related article
Characterization of maximal enzyme catalytic rates in central metabolism of Arabidopsis thaliana
Authors: Küken Anika , Gennermann Kristin , Nikoloski Zoran
Published: July 2020

Availability of plant‐specific enzyme kinetic data is scarce, limiting the predictive power of metabolic models and precluding identification of genetic factors of enzyme properties. Enzyme kinetic data are measured in vitro, often under non‐physiological conditions, and conclusions elicited from modeling warrant caution. Here we estimate maximal in vivo catalytic rates for 168 plant enzymes, including photosystems I and II, cytochrome‐b6f complex, ATP‐citrate synthase, sucrose‐phosphate synthase as well as enzymes from amino acid synthesis with previously undocumented enzyme kinetic data in BRENDA. The estimations are obtained by integrating condition‐specific quantitative proteomics data, maximal rates of selected enzymes, growth measurements from Arabidopsis thaliana rosette with and fluxes through canonical pathways in a constraint‐based model of leaf metabolism. In comparison to findings in Escherichia coli, we demonstrate weaker concordance between the plant‐specific in vitro and in vivo enzyme catalytic rates due to a low degree of enzyme saturation. This is supported by the finding that concentrations of nicotinamide adenine dinucleotide (phosphate), adenosine triphosphate and uridine triphosphate, calculated based on our maximal in vivo catalytic rates, and available quantitative metabolomics data are below reported values and, therefore, indicate undersaturation of respective enzymes. Our findings show that genome‐wide profiling of enzyme kinetic properties is feasible in plants, paving the way for understanding resource allocation.
An internally eGFP‐tagged α‐adaptin is a fully functional and improved fiduciary marker for clathrin‐coated pit dynamics
Authors: Mino Rosa E. , Chen Zhiming , Mettlen Marcel , Schmid Sandra L.
Published: July 2020

Clathrin mediated endocytosis (CME) has been extensively studied in living cells by quantitative total internal reflection fluorescence microscopy (TIRFM). Fluorescent protein fusions to subunits of the major coat proteins, clathrin light chains or the heterotetrameric adaptor protein (AP2) complexes, have been used as fiduciary markers of clathrin coated pits (CCPs). However, the functionality of these fusion proteins has not been rigorously compared. Here, we generated stable cells lines overexpressing mRuby‐CLCa and/or μ2‐eGFP, σ2‐eGFP, two markers currently in use, or a novel marker generated by inserting eGFP into the unstructured hinge region of the α subunit (α‐eGFP). Using biochemical and TIRFM‐based assays, we compared the functionality of the AP2 markers. All of the eGFP‐tagged subunits were efficiently incorporated into AP2 and displayed greater accuracy in image‐based CCP analyses than mRuby‐CLCa. However, overexpression of either μ2‐eGFP or σ2‐eGFP impaired transferrin receptor uptake. In addition, μ2‐eGFP reduced the rates of CCP initiation and σ2‐eGFP perturbed AP2 incorporation into CCPs and CCP maturation. In contrast, CME and CCP dynamics were unperturbed in cells overexpressing α‐eGFP. Moreover, α‐eGFP was a more sensitive and accurate marker of CCP dynamics than mRuby‐CLCa. Thus, our work establishes α‐eGFP as a robust, fully functional marker for CME.
Indirect effects in predator-prey interaction: development and predation rates by immature Neoseiulus cucumeris increased by odour from its prey (Tyrophagus putrescentiae)

Authors: Gu Xin-yao , Li Guang-yun , Zhang Zhi-qiang
Published: July 2020

Predator-prey interactions have long been of great interest to ecologists. Although the direct consumptive effects have received extensive research, indirect influences of odour derived from their conspecifics and prey on predators have largely been underestimated and overlooked. In this study, the indirect effects of predator-prey interactions were determined with predatory mites Neoseiulus cucumeris and its factitious prey Tyrophagus putrescentiae. The responses of immature N. cucumeris to mixed odour with their conspecifics and prey were determined in a laboratory experiment. Our results showed that the mixed odour with their conspecifics did not demonstrate any obvious influences on the survival rates, developmental periods, predation rates and activities of the predatory mites. Intriguingly, the predators prolonged their protonymphal stage and consumed more prey eggs when exposed to mixed odour with their prey. Our results indicated that the mixed odour with their conspecifics was weak and its influence was insignificant for this species, but the prey odour showed a signifcant influence on the growth and consumption rates of immature predators, which highlighted that the indirect influences of predator-prey interactions on the predator were substantial and cannot be neglected.
Enhanced sputter and secondary ion yields using MeV gold nanoparticle beams delivered by the Andromede facility
Authors: Lai Thanh Loan , Jacquet Dominique , Ribaud Isabelle , Eller Michael John , Verkhoturov Dmitriy , Schweikert Emile Albert , Tizei Luiz Henrique Galvão , Shao Fuhui , Bilgen Suheyla , Mercier Bruno , Sattonnay Gael , Della Negra Serge
Published: July 2020

Andromede is a new instrument for mass spectrometry analysis of nanodomains and nano-objects present on a surface. The molecular sample information (mass and structure) is obtained from time-of-flight spectra of secondary ions emitted under the impact of nanoparticles (NPs), as Aunq+ with n/q up to 200 accelerated by a 4 MV single stage electrostatic Pelletron® accelerator. Such projectiles, providing huge emission rates per impact, permit the topographic analysis of complex samples. The energy deposition of these massive gold NPs induces surprisingly large holes of about 100 nm diameter in very thin graphene foils and average sputtered volume per impact of about 106 nm3 in a thick polymer material. The use of such massive clusters associated with multianode detectors, allowing the simultaneous detection of several ions of a given mass, permits correlation studies between the emitted ions within a single impact, shedding additional light on the chemical composition and structure of the analysed sample as illustrated here for various samples from metallic surfaces to biologic molecules deposits.