bluuebunny/crossref_metadata_2025 huggingface dataset:
The neuropsychiatric phenotype in CACNA1A mutations: a retrospective single center study and review of the literature
Authors: Indelicato E. , Nachbauer W. , Karner E. , Eigentler A. , Wagner M. , Unterberger I. , Poewe W. , Delazer M. , Boesch S.
Published: July 2018

Background and purpose

CACNA1A encodes the α1 subunit of the neuronal calcium channel P/Q. CACNA1A mutations underlie three allelic disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). A clear‐cut genotype–phenotype correlation is often lacking since clinical manifestations may overlap. Several case reports have described cognitive and behavioral features in CACNA1A disorders, but studies in larger case series are lacking.

Methods

Genetically confirmed CACNA1A cases were retrieved from the database of the ataxia outpatient clinic of the Department of Neurology at Innsbruck Medical University. Clinical charts and neuropsychological test results were retrospectively analyzed. In addition, a review of the literature including only genetically confirmed cases was performed.

Results

Forty‐four CACNA1A cases were identified in our database. Delayed psychomotor milestones and poor school performance were described in seven (four FHM1, three EA2) and eight (three FHM1, five EA2) patients, respectively. Psychiatric comorbidities were diagnosed in eight patients (two FHM1, six EA2). Neuropsychological testing was available for 23 patients (11 FHM1, 10 EA2, two SCA6). Various cognitive deficits were documented in 21 cases (all patients except one SCA6). Impairments were predominantly seen in figural memory, visuoconstructive abilities and verbal fluency. In the literature, an early psychomotor delay is described in several children with EA2 and FHM1, whilst reports of cognitive and psychiatric findings from adult cases are scarce.

Conclusions

Neuropsychiatric manifestations are common in episodic CACNA1A disorders. In the case of otherwise unexplained developmental delay and a positive family history, CACNA1A mutations should be considered in the differential diagnosis.
Patient and public engagement in research and health system decision making: A systematic review of evaluation tools
Authors: Boivin Antoine , L'Espérance Audrey , Gauvin François‐Pierre , Dumez Vincent , Macaulay Ann C. , Lehoux Pascale , Abelson Julia
Published: July 2018

Background

Patient and public engagement is growing, but evaluative efforts remain limited. Reviews looking at evaluation tools for patient engagement in individual decision making do exist, but no similar articles in research and health systems have been published.

Objective

Systematically review and appraise evaluation tools for patient and public engagement in research and health system decision making.

Methods

We searched literature published between January 1980 and February 2016. Electronic databases (Ovid MEDLINE, Embase, Cochrane Database of Systematic Reviews, CINAHL and PsycINFO) were consulted, as well as grey literature obtained through Google, subject‐matter experts, social media and engagement organization websites. Two independent reviewers appraised the evaluation tools based on 4 assessment criteria: scientific rigour, patient and public perspective, comprehensiveness and usability.

Results

In total, 10 663 unique references were identified, 27 were included. Most of these tools were developed in the last decade and were designed to support improvement of engagement activities. Only 11% of tools were explicitly based on a literature review, and just 7% were tested for reliability. Patients and members of the public were involved in designing 56% of the tools, mainly in the piloting stage, and 18.5% of tools were designed to report evaluation results to patients and the public.

Conclusion

A growing number of evaluation tools are available to support patient and public engagement in research and health system decision making. However, the scientific rigour with which such evaluation tools are developed could be improved, as well as the level of patient and public engagement in their design and reporting.
Impact of processing parameters and post‐treatment on the shape accuracy of 3D‐printed baking dough
Authors: Yang Fan , Zhang Min , Fang Zhongxiang , Liu Yaping
Published: July 2018

Apart from the material compositions, processing parameters of a 3D printer also affect the modelling effect of printed samples. This paper presents the influence of processing parameters including filament diameter (2.10, 2.30, 2.50 mm), nozzle movement speed (20, 25, 30 mm/s), nozzle diameter (0.8, 1.5, 2.0 mm) and nozzle height (2.10, 2.40, 2.60 mm), as well as that of post‐process fast‐cooling (−65 °C; 0, 5, 10 min), on the rheological properties and geometric accuracy of a 3D‐printed food construct made of baking dough (BD). Results showed that the printed object whose shape best matched the target geometry could be obtained with the following processing parameters: filament diameter of 2.30 mm, nozzle movement speed of 25 mm/s, nozzle diameter of 2.0 mm and nozzle height of 2.40 mm during 3D printing, combined with fast‐cooling at −65 °C for more than 10 min after printing and before baking.
Different sides of the same conversation: Black and White partners differ in perceptions of interaction content
Authors: Olson Michael A. , Johnson Camille S. , Zabel Kevin L. , Phillips Joy E.
Published: July 2018

A positive interracial interaction can create a foundation for friendships, improved intergroup attitudes and reduced prejudice. Recent research has demonstrated that what people talk about in important. Here, two studies expand the interaction content model of interracial interactions to reveal that Black and White Americans perceive interaction content in similar and different ways. As expected, Black and White participants evaluated conversation topics along the same three dimensions, but differed in their perceptions of specific conversation topics. These convergences and differences emerged for pre‐generated (Study 1) and self‐generated (Study 2) topics. Factor analyses revealed that conversation attributes similarly distilled to the predicted underlying content dimensions of intimacy, valence, and controversy for Black and White Americans. However, Black individuals found interaction content, in general, to be more controversial, race‐related, enjoyable, and predictable than White individuals. Although both groups found race‐related content more controversial, Black individuals were less bothered by discussing race and found race‐related topics to be more predictable and enjoyable to discuss. These findings supported the interaction content model which may provide a framework for future research on interracial interactions. We conclude with the importance of considering differences in perceptions of interaction content, as well as suggestions for how intergroup interaction research could benefit from systematically incorporating such content.
Naturalized plants decrease diet similarity between an invasive bird and its most similar native species
Authors: Cardoso Gonçalo C. , Rodrigues Gonçalo Carvalho , Alves Paulo , Vicente Joana R. , Honrado João P.
Published: July 2018

Although invasive animals can compete with native species for resources, detrimental competition for food is seldom reported in the avian invasions literature. In temperate climates, food limitation and energetic stress are higher during winter and, thus, winter diets might reveal competition that is not apparent during the rest of the year. We compared autumn and winter diets of the invasive common waxbill Estrilda astrild in northwest Iberia, and of the native bird most similar to it in foraging behaviour, the European serin Serinus serinus. Both bird species forage for seeds in open habitats, mostly in or around agricultural areas. We found that food preferences of the two species were substantially different when foraging on the same agricultural landscape. Contrary to the prediction that food scarcity in winter would make diets more similar, the diets of waxbills and serins diverged in winter, indicating low potential for detrimental interspecific competition. Differences in diet were in part due to foraging on non‐native plants. Non‐native seeds represented a large part of the waxbill diet in autumn (a non‐native grass), and a small part of serin's (a non‐native forb), substantially decreasing their diet similarity. Our results are consistent with the view that waxbills are using a vacant niche in human‐modified habitats, in this case involving non‐crop plants associated with agricultural practices (e.g. irrigation, tillage, harvest) that are underexploited by the native fauna. Understanding which invasive animals fill those vacant niches and, thus, may interfere minimally with native faunas, helps to prioritize conservation actions.
Migration distance affects stopover use but not travel speed: contrasting patterns between long‐ and short‐distance migrating ospreys
Authors: Monti Flavio , Grémillet David , Sforzi Andrea , Dominici Jean Marie , Bagur Rafel Triay , Navarro Antoni Muñoz , Fusani Leonida , Klaassen Raymond H. G. , Alerstam Thomas , Duriez Olivier
Published: July 2018

The development of migratory behaviour is a continuous process which is not only determined by genes, but also moulded by individual differences based on life‐history variations occurring at each ontogenetic stage. Assessing consistency and plasticity in migratory traits between long distance (LDM) and short distance migratory (SDM) populations within the same species that may express dissimilarities in the leeway of annual schedules is essential to understand the evolution and ontogeny of migratory strategies.

We studied the migration strategies in autumn regarding flight speed and the use of stopovers (number and duration of stop‐overs across the whole journey) at the intra‐specific level, by tracking with GPS loggers the intercontinental migration of 43 adult and juvenile ospreys Pandion haliaetus from both LDM and SDM populations.

LDM ospreys travelled distances five times larger than SDM ospreys, but their total migration speed was 2.4 times slower. While daily distance travelled did not differ between populations, the reduced total migration speed by LDMs was due to higher stopover use compared to SDM birds. SDM birds used more direct routes, crossing open sea at higher flight speeds, even though both populations largely benefitted from wind assistance across their journey. Across populations, adult birds travelled longer distances per day and displayed less sinuous migratory paths than juveniles, suggesting that migratory capabilities improve with age and experience of the bird. Overall, the time constraint related to total migration distance was not the main driver of the total migration speed, and other factors such as physiological needs to rest and refuel at stopover sites may play an important role. Our study underlines the importance of investigating variability in migration strategies in partially migratory species, for a better understanding of avian migratory ecology.
A systematic review of the use of ketogenic diets in adult patients with cancer
Authors: Sremanakova J. , Sowerbutts A. M. , Burden S.
Published: July 2018

Background

A growing body of evidence indicates the importance of nutrition in cancer treatment. Ketogenic diets are one strategy that has been proposed to enhance traditional anticancer therapy. This review summarises the evidence concerning the effect of oral ketogenic diets on anthropometry, metabolism, quality of life (QoL) and tumour effects, at the same time as documenting adverse events and adherence in patients with cancer.

Methods

We searched electronic databases using medical subject headings (MeSH) and text words related to ketogenic diets and cancer. Adult patients following a ketogenic diet as a complementary therapy prior, alongside or after standard anticancer treatment for more than 7 days were included. Studies were assessed for quality using the Critical Appraisal Skills Programme tools (https://www.casp-uk.net).

Results

Eleven studies were included with 102 participants (age range 34–87 years) from early‐phase trials, cohort studies and case reports. Studies included participants with brain, rectal or mixed cancer sites at an early or advanced disease stage. The duration of intervention ranged from 2.4 to 134.7 weeks (0.5–31 months). Evidence was inconclusive for nutritional status and adverse events. Mixed results were observed for blood parameters, tumour effects and QoL. Adherence to diet was low (50 out of 102; 49%) and ranged from 23.5% to 100%.

Conclusions

High‐quality evidence on the effect of ketogenic diets on anthropometry, metabolism, QoL and tumour effects is currently lacking in oncology patients. Heterogeneity between studies and low adherence to diet affects the current evidence. There is an obvious gap in the evidence, highlighting the need for controlled trials to fully evaluate the intervention.
Vaccinia‐related kinase 2 modulates role of dysbindin by regulating protein stability
Authors: Jeong Young‐Hun , Choi Jung‐Hyun , Lee Dohyun , Kim Sangjune , Kim Kyong‐Tai
Published: July 2018

Vaccinia‐related kinase 2 (VRK2) is a serine/threonine kinase that belongs to the casein kinase 1 family. VRK2 has long been known for its relationship with neurodegenerative disorders such as schizophrenia. However, the role of VRK2 and the substrates associated with it are unknown. Dysbindin is known as one of the strong risk factors for schizophrenia. The expression of dysbindin is indeed significantly reduced in schizophrenia patients. Moreover, dysbindin is involved in neurite outgrowth and regulation of NMDA receptor signaling. Here, we first identified dysbindin as a novel interacting protein of VRK2 through immunoprecipitation. We hypothesized that dysbindin is phosphorylated by VRK2 and further that this phosphorylation plays an important role in the function of dysbindin. We show that VRK2 phosphorylates Ser 297 and Ser 299 of dysbindin using in vitro kinase assay. In addition, we found that VRK2‐mediated phosphorylation of dysbindin enhanced ubiquitination of dysbindin and consequently resulted in the decrease in its protein stability through western blotting. Over‐expression of VRK2 in human neuroblastoma (SH‐SY5Y) cells reduced neurite outgrowth induced by retinoic acid. Furthermore, a phosphomimetic mutant of dysbindin alleviated neurite outgrowth and affected surface expression of N‐methyl‐d‐aspartate 2A, a subunit of NMDA receptor in mouse hippocampal neurons. Together, our work reveals the regulation of dysbindin by VRK2, providing the association of these two proteins, which are commonly implicated in schizophrenia.

Open science badges

This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

image
Effects of medicines used to treat gastrointestinal diseases on the pharmacokinetics of coadministered drugs: a PEARRL Review
Authors: Litou Chara , Effinger Angela , Kostewicz Edmund S , Box Karl J , Fotaki Nikoletta , Dressman Jennifer B
Published: July 2018

Objectives

Drugs used to treat gastrointestinal diseases (GI drugs) are widely used either as prescription or over-the-counter (OTC) medications and belong to both the 10 most prescribed and 10 most sold OTC medications worldwide. The objective of this review article is to discuss the most frequent interactions between GI and other drugs, including identification of the mechanisms behind these interactions, where possible.

Key findings

Current clinical practice shows that in many cases, these drugs are administered concomitantly with other drug products. Due to their metabolic properties and mechanisms of action, the drugs used to treat gastrointestinal diseases can change the pharmacokinetics of some coadministered drugs. In certain cases, these interactions can lead to failure of treatment or to the occurrence of serious adverse events. The mechanism of interaction depends highly on drug properties and differs among therapeutic categories. Understanding these interactions is essential to providing recommendations for optimal drug therapy.

Interactions with GI drugs are numerous and can be highly significant clinically in some cases. While alterations in bioavailability due to changes in solubility, dissolution rate, GI transit and metabolic interactions can be (for the most part) easily identified, interactions that are mediated through other mechanisms, such as permeability or microbiota, are less well-understood. Future work should focus on characterising these aspects.
In-line derivative spectroscopy as a promising application to a small-scale in vitro transfer model in biorelevant supersaturation and precipitation testing
Authors: Jede Christian , Wagner Christian , Kubas Holger , Weber Christian , Weitschies Werner
Published: July 2018

Objectives

Dissolution testing of poorly soluble and precipitating drugs is of great importance for pharmaceutical industry. As offline HPLC analytics is time-consuming and labour-intensive, the development of suitable in-line analytics to measure drug concentration allows better predictions of drug dissolution and precipitation. The purpose of this study was to develop an in-line derivative spectroscopic method which facilitates drug concentration measurements in suspensions without additional sample preparation.

Methods

Solubility, dissolution and precipitation of ketoconazole were analysed using derivative spectroscopy and HPLC.

Key findings

Results of solubility and dissolution experiments were highly comparable. Due to higher sampling frequency and lack of sample preparations, supersaturation in a pH-shift experiment was more accurately captured by UV in-line analytics. The application of a prefiltration step and flow-through cuvettes facilitates implementation of in-line derivative spectroscopy into an in vitro transfer model with changing UV-active media and high supersaturation in highly turbid samples.

Conclusions

Although the application of derivative spectroscopy has been described previously, the approach described herein is novel and well-suited for the application in an automated in vitro transfer model. Moreover, it represents a promising tool for drug substance characterisation, candidate selection and formulation development.
Employment and fiscal policy in a Marxian model
Authors: Thompson Stephen
Published: July 2018

This article presents a simple formalization of Marx's circuit of capital framework, but with some modern additions: a public sector, an investment function that shifts over time in reaction to disequilibria, and a ‘wage curve’ linking income distribution to the size of the reserve army of labor. The dynamics can gravitate toward either a low‐employment trajectory in which public spending has expansionary long‐run effects, or a high‐employment trajectory characterized by a profit squeeze. The stability of the different trajectories depends on the investment function.
Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging
Authors: Major G. , Murray K. , Singh G. , Nowak A. , Hoad C. L. , Marciani L. , Silos‐Santiago A. , Kurtz C. B. , Johnston J. M. , Gowland P. , Spiller R.
Published: July 2018

Background

In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls.

Methods

Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days – maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured.

Results

7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284‐601) to 578 mL (IQR 510‐882), and in patients from median 831 mL (IQR 745‐934) to 1104 mL (847‐1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176‐420) than controls (440 ms, 352‐884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446‐1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment.

Conclusions and Inferences

MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.
Effect of attention bias modification on event‐related potentials in patients with irritable bowel syndrome: A preliminary brain function and psycho‐behavioral study
Authors: Tayama J. , Saigo T. , Ogawa S. , Takeoka A. , Hamaguchi T. , Inoue K. , Okamura H. , Yajima J. , Matsudaira K. , Fukudo S. , Shirabe S.
Published: July 2018

Background

Attention bias modification normalizes electroencephalographic abnormalities in alpha and beta power percentages related to attention in patients with irritable bowel syndrome (IBS). Yet, it is unknown whether ABM contributes to the normalization of event‐related potentials (ERP) in these patients. We hypothesized that ERP related to attention deficit would be normalized after ABM implementation in individuals with IBS.

Methods

Thirteen patients with IBS and 10 control subjects completed a 2‐month intervention that included five ABM sessions. Each session included 128 trials, resulting in a total of 640 trials during the study period. Event‐related potentials were measured at the first and fifth sessions. As per the international 10‐20 system for electroencephalographic electrode placement, right parietal P4 was evaluated to measure the attention component of facial expression processing.

Key Results

A group comparison of P100 latency at P4 revealed that latencies were significantly different between groups in session 1 (IBS vs control, 108 ± 8 vs 97 ± 14; t = −2.51, P = .0203). This difference was absent in session 5 (94 ± 11 vs 93 ± 11, respectively; t = −0.397, P = .6954, r = .09), indicating an effect of ABM in the IBS group.

Conclusions and inferences

Attention bias modification may have clinical utility for normalizing brain function and specifically attentional abnormalities in patients with IBS.
Regional gastrointestinal pH profile is altered in patients with type 1 diabetes and peripheral neuropathy
Authors: Wegeberg A.‐M. L. , Brock C. , Brock B. , Farmer A. D. , Hobson A. R. , Semler J. R. , Scott S. M.
Published: July 2018

Background

Gastrointestinal (GI) symptoms, such as nausea and bloating, are common in people with type 1 diabetes (T1DM). Autonomic dysfunction can lead to changes in the GI secreto‐motor function which can be associated with GI symptom development. We hypothesized that regional pH profiles in T1DM differs from health and would be associated with objective physiological/clinical markers.

Methods

Forty‐seven T1DM with confirmed diabetic sensory peripheral neuropathy and 41 healthy age‐matched subjects underwent standardized wireless motility capsule testing. T1DM completed the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale. Disease duration, glycemic control, insulin usage, and 24‐hour heart rate variability testing were evaluated.

Key Results

In comparison to healthy subjects, gastric, and large bowel median pH were lower in T1DM (1.8 ± 1.6 vs 2.9 ± 1.5, P = 0.001 and 6.7 ± 0.6 vs 7.0 ± 0.5, P = 0.003, respectively). Additionally, change in pH across the pylorus was lower while change in pH across the ileocecal junction was higher in T1DM (5.2 ± 1.5 vs 5.8 ± 0.5, P = 0.003 and 1.8 ± 0.4 vs 1.3 ± 0.4, P < 0.0001, respectively). No difference was found in small bowel median pH. Gastric median pH was associated with small bowel transit time (r = 0.30, P = 0.049). Change in pH across the pylorus was negatively associated with fasting glycose (r = −0.35, P = 0.027). Small bowel median pH was associated with nausea (r = 0.42, P = 0.005) and small bowel transit time (r = 0.48, P = 0.0007). Large bowel median pH was associated with nausea (r = 0.35, P = 0.018) and the total GCSI score (r = 0.34, P = 0.023).

Conclusions and Inferences

The GI pH profile in T1DM with DSPN is different from healthy subjects. Changes in pH profile may have important therapeutic implications and influence pharmacotherapeutic bioavailability.
Three Arguments to Think that Faith Does Not Entail Belief
Authors: Howard‐Snyder Daniel
Published: July 2018

On doxastic theories of propositional faith, necessarily, S has faith that p only if S believes that p. On nondoxastic theories of propositional faith, it's false that, necessarily, S has faith that p only if S believes that p. In this article, I defend three arguments for nondoxastic theories of faith and I respond to published criticisms of them.
Supply Diagnostic Incentives under Endogenous Information Asymmetry
Authors: Nikoofal Mohammad E. , Gümüş Mehmet
Published: July 2018

This paper develops a dyadic supply chain model with one buyer who contracts the manufacturing of a new product to a supplier. Due to the lack of experience in manufacturing, the extent of supply risk is unknown to both the buyer and supplier before the time of contract. However, after the contract is accepted, the supplier may invest in a diagnostic test to acquire information about his true reliability, and use this information when deciding on a process improvement effort. Using this setting, we identify both operational and strategic benefits and costs of the diagnostic test. Operationally, it helps the supplier to take the first‐best level of improvement effort, which would increase efficiency of the total supply chain. Strategically, it enables the buyer to reduce the agency costs associated with implementing process improvement on the supplier. Besides these benefits, diagnostic test increases the degree of information asymmetry along the supply chain. This in turn provides the supplier with proprietary information, whose rent would be demanded from the buyer in equilibrium. Benefit‐cost analysis reveals two key factors in determining the value of diagnostic test: (i) degree of endogenous information asymmetry between supply chain firms, and (ii) the relative cost of a diagnostic test with respect to process improvement cost. Our results indicate that when both are high, the mere presence of a diagnostic test can result in less reliable supply chain. This implies that when incentives are not properly aligned, information asymmetry amplified due to diagnostic test neutralizes all its benefits.
Improving Remanufacturing Core Recovery and Profitability Through Seeding
Authors: Abbey James D. , Geismar H. Neil , Souza Gilvan C.
Published: July 2018

Through analytical modeling and a numerical study grounded in observations from automotive remanufacturing, this study examines seeding—selling new products as remanufactured at the start of a new product's lifecycle—in order to increase core recovery quantities, to allow firms to start efficient remanufacturing earlier, and to fulfill demand for remanufactured products throughout the product's lifecycle. Though seeding has received little attention in the academic literature, many durable goods industries, such as automotive parts and heavy equipment remanufacturing, employ seeding because a lack of used units (cores) significantly constrains their remanufacturing operations. The results reveal that the cost of producing a new unit and the shape of the product lifecycle curve are key determinants of the profitability of seeding. Specifically, if the price of the remanufactured product is less than the cost of producing a new unit, then the profitability of seeding is impacted negatively when the product lifecycle ramps up slowly or when there is a large time lag for the recovery of seeded units. In effect, initial sales of seeded units at a loss for a longer period reduces and potentially nullifies the benefits of seeding. Conversely, if initial sales of seeded units are profitable, then a slower ramp‐up of the product lifecycle or a large time lag for the recovery of seeded units has a positive impact on the profitability of seeding because seeding under these circumstances allows the firm to meet demand for remanufactured products profitably earlier in the lifecycle. The results from a numerical study indicate that seeding increases total remanufacturing profits by an average of 23% and a maximum of 40% over the product's lifecycle.
The choice between uniqueness and conformity in mass customization
Authors: Zaggl Michael A. , Hagenmaier Markus A. , Raasch Christina
Published: July 2018

Extant research emphasizes that consumers use mass customization toolkits to create products they consider to be unique, and that perceived uniqueness is an important part of customer value. This research investigates the conditions of the customer's quest for uniqueness. It is motivated by the observation that decisions are often driven by others’ choices and a desire to fit in, rather than to be distinct. We hypothesize that consumers are more inclined to choose uniqueness for hedonic product attributes but tend toward conformity in utilitarian attributes, and that consumers’ need for uniqueness and product involvement moderate the choice. In a series of experiments, we find support for most hypotheses. We introduce conformity as a driver of choice behavior in mass customization toolkits and suggest that mass customization can best be seen as enabling consumers’ preferred mix of uniqueness and conformity. Our results also inform managerial practice, highlighting that mass customization toolkits should consider customers’ uniqueness and conformity requirements. We suggest reducing the number of utilitarian options while increasing the variety for hedonic attributes.
Fundamental differences in starch synthesis in the maize leaf, embryo, ovary and endosperm
Authors: Boehlein Susan K. , Shaw Janine R. , Boehlein Timothy J. , Boehlein Emily C. , Hannah L. Curtis
Published: July 2018

Enzymological and starch analyses of various ADP‐glucose pyrophosphorylase (AGPase) null mutants point to fundamental differences in the pathways for starch synthesis in the maize leaf, embryo, ovary and endosperm. Leaf starch is synthesized via the AGPase encoded by the small and large subunits shown previously to be expressed at abundant levels in the leaf, whereas more than one AGPase isoform functions in the embryo and in the ovary. Embryo starch content is also dependent on genes functioning in the leaf and in the endosperm. AGPase encoded by shrunken‐2 and brittle‐2 synthesizes ~75% of endosperm starch. The gene, agpsemzm, previously shown to encode the small subunit expressed in the embryo, and agpllzm, the leaf large subunit gene, are here shown to encode the endosperm, plastid‐localized AGPase. Loss of this enzyme does not reduce endosperm starch. Rather, the data suggest that AGPase‐independent starch synthesis accounts for ~25% of endosperm starch. Three maize genes encode the small subunit of the AGPase. Data here show that the triple mutant lacking all three small subunits is lethal in early seed development but can be viable in both male and female gametes. Seed and plant viability is restored by any one of the three small subunit genes, including one previously thought to function only in the cytosol of the endosperm. Data herein also show the functionality of a fourth gene encoding the large subunit of this enzyme. Although adenosine diphosphate glucose pyrophosphorylase is shown here to be essential for maize viability, strong evidence for starch synthesis in the endosperm that is independent of this enzyme is also presented. Starch synthesis is distinct in the maize embryo, ovary, leaf and endosperm, and is coordinated among the various tissues.
Protocol for the first clinical trial to investigate safety and efficacy of corneal xenotransplantation in patients with corneal opacity, corneal perforation, or impending corneal perforation
Authors: Choi Hyuk Jin , Yoon Chang Ho , Hyon Joon Young , Lee Hyung Keun , Song Jong‐Suk , Chung Tae‐Young , Mo Hyojung , Kim Jaeyoung , Kim Jae‐eun , Hahm Bong‐Jin , Yang Jaeseok , Park Wan Beom , Kim Mee Kum
Published: July 2018

Background

Xenotransplantation using fresh porcine corneas has been suggested as a feasible alternative to overcome the shortage of human donor corneas. Successful long‐term survival of grafts without evidence of xenozoonosis in clinically applicable pig‐to‐non‐human primate corneal transplantation model has brought researchers close to human clinical trials. Accordingly, we aimed to prepare a clinical trial protocol to conduct the first corneal xenotransplantation.

Methods

We developed the clinical trial protocol based on international consensus statement on conditions for undertaking clinical trials of corneal xenotransplantation developed by the International Xenotransplantation Society. Detailed contents of the protocol have been modified with reference to comments provided by ophthalmologists and multidisciplinary experts, including an infectionist, an organ transplantation specialist, a clinical pharmacologist, a neuropsychiatrist, a laboratory medicine doctor, and a microbiologist.

Results

Two patients with bilateral legal corneal blindness (best‐corrected visual acuity ≤20/200 in the better eye and ≤20/1000 in the candidate eye) or with (impending) corneal perforation will be enrolled. During the screening period, participants and their family members will have two separate deep consideration periods before signing informed consent forms. Each patient will undergo corneal xenotransplantation using fresh corneas from Seoul National University miniature pigs. Commercially available immunosuppressants will be administered and systemic infection prophylaxis will be performed according to the program schedule. After transplantation, each patient will be monitored at a specialized clinic to investigate safety up to 2 years and efficacy up to 1 year.

Conclusions

A detailed clinical trial protocol for the first corneal xenotransplantation reflecting the global guidelines is provided.
The Effect of Balance and Stability Workouts on the Development of Static and Dynamic Balance in 10-12-Year-Old Soccer Players
Authors: Tanır Halil
Published: July 2018

The purpose of this study is to explore the effect of balance and stability workouts on the development of static and dynamic balance in 10-12-year-old soccer players. The sample of the study was 40 soccer players (n=20 control and n=20 experimental) aged 10-12 years (age=11.2±08). Besides daily training program, soccer players in the experimental group participated in an extra 8-week fitness program which included bosu & swiss ball workouts, balance board workouts, plyometric workouts and bodyweight core stability workouts. Soccer players in the control group only continued their daily routine training. The static and dynamic balance performances of the players in the experimental and control groups were measured using Flamingo Balance Test (FBT) and Star Excursion Balance Test (SEBT) before and after the 8-week fitness program. Statistical analysis demonstrated significant differences between pre and post test results regarding both static and dynamic balance performance of the players in the experimental group (p<0.05). Based on the findings, it was concluded that the 8-week fitness program which included bosu & swiss ball workouts, balance board workouts, plyometric workouts and bodyweight core stability workouts contributed to the static and dynamic balance development in 10-12-year-old soccer players.
Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye
Authors: Sakurai Tetsuya , Uruno Takehito , Sugiura Yuki , Tatsuguchi Takaaki , Yamamura Kazuhiko , Ushijima Miho , Hattori Yuko , Kukimoto-Niino Mutsuko , Mishima-Tsumagari Chiemi , Watanabe Mayuki , Suematsu Makoto , Fukui Yoshinori
Published: July 2018

A modified form of cholesterol protects the eye from immune cell invasion by inhibiting the Rac-specific GEF DOCK2.
Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis
Authors: Illamola Sílvia M. , Huynh Hoa Q. , Liu Xiaoxi , Bhakta Zubin N. , Sherwin Catherine M. , Liou Theodore G. , Carveth Holly , Young David C.
Published: July 2018

Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy.
Characterization of Mutations Conferring Resistance to Rifampin in Mycobacterium tuberculosis Clinical Strains
Authors: Jagielski Tomasz , Bakuła Zofia , Brzostek Anna , Minias Alina , Stachowiak Radosław , Kalita Joanna , Napiórkowska Agnieszka , Augustynowicz-Kopeć Ewa , Żaczek Anna , Vasiliauskiene Edita , Bielecki Jacek , Dziadek Jarosław
Published: July 2018

Resistance ofMycobacterium tuberculosisto rifampin (RMP), mediated by mutations in therpoBgene coding for the beta-subunit of RNA polymerase, poses a serious threat to the efficacy of clinical management and, thus, control programs for tuberculosis (TB). The contribution of many individualrpoBmutations to the development and level of RMP resistance remains elusive.
High-Resolution Analysis of the Peptidoglycan Composition in Streptomyces coelicolor
Authors: van der Aart Lizah T. , Spijksma Gerwin K. , Harms Amy , Vollmer Waldemar , Hankemeier Thomas , van Wezel Gilles P.
Published: July 2018

Streptomycetes are bacteria with a complex lifestyle and are model organisms for bacterial multicellularity. From a single spore, a large multigenomic multicellular mycelium is formed, which differentiates to form spores. Programmed cell death is an important event during the onset of morphological differentiation. In this work, we provide new insights into the changes in the peptidoglycan composition and over time, highlighting changes over the course of development and between growing mycelia and spores. This revealed dynamic changes in the peptidoglycan when the mycelia aged, with extensive peptidoglycan hydrolysis and, in particular, an increase in the proportion of 3-3 cross-links. Additionally, we identified a muropeptide that accumulates predominantly in the spores and may provide clues toward spore development.
Role for GrgA in Regulation of σ
28
-Dependent Transcription in the Obligate Intracellular Bacterial Pathogen Chlamydia trachomatis
Authors: Desai Malhar , Wurihan Wurihan , Di Rong , Fondell Joseph D. , Nickels Bryce E. , Bao Xiaofeng , Fan Huizhou
Published: July 2018

Chlamydia trachomatis
is the number one sexually transmitted bacterial pathogen worldwide. A substantial proportion of
C. trachomatis
-infected women develop infertility, pelvic inflammatory syndrome, and other serious complications.
C. trachomatis
is also a leading infectious cause of blindness in underdeveloped countries. The pathogen has a unique developmental cycle that is transcriptionally regulated. The discovery of an expanded role for the
Chlamydia-
specific transcription factor GrgA helps us understand the progression of the chlamydial developmental cycle.
Biochemical and Phylogenetic Study of SltF, a Flagellar Lytic Transglycosylase from Rhodobacter sphaeroides
Authors: García-Ramos Mariela , de la Mora Javier , Ballado Teresa , Camarena Laura , Dreyfus Georges
Published: July 2018

Flagellar biogenesis is a highly orchestrated event where the flagellar structure spans the bacterial cell envelope. The rod diameter of approximately 4 nm is larger than the estimated pore size of the peptidoglycan layer; hence, its insertion requires the localized and controlled lysis of the cell wall. We found that a 47-residue domain of the C terminus of the lytic transglycosylase (LT) SltF of
R. sphaeroides
is involved in the recognition of the rod chaperone FlgJ. We also found that in many alphaproteobacteria, the flagellar cluster includes a homolog of SltF and FlgJ, indicating that association of an LT with the flagellar machinery is ancestral. A maximum likelihood tree shows that family 1 of LTs segregates into seven subfamilies.
Functional Study of the C-Terminal Part of the Hepatitis C Virus E1 Ectodomain
Authors: Moustafa Rehab I. , Haddad Juliano G. , Linna Lydia , Hanoulle Xavier , Descamps Véronique , Mesalam Ahmed Atef , Baumert Thomas F. , Duverlie Gilles , Meuleman Philip , Dubuisson Jean , Lavie Muriel
Published: July 2018

HCV is a major public health problem worldwide. The virion harbors two envelope proteins, E1 and E2, which are involved at different steps of the viral life cycle. Whereas E2 has been extensively characterized, the function of E1 remains poorly defined. We characterized here the function of the putative fusion peptide and the region containing α helices of the E1 ectodomain, which had been previously suggested to be important for virus entry. We could confirm the importance of these regions for the virus infectivity. Interestingly, we found several residues modulating the virus's dependence on several HCV receptors, thus highlighting the role of E1 in the interaction of the virus with cellular receptors. Whereas mutations in the putative fusion peptide affected HCV infectivity and morphogenesis, several mutations in the α2-helix region led to a loss of infectivity with no effect on assembly, indicating a role of this region in virus entry.
A Novel
Shigella
Proteome Microarray Discriminates Targets of Human Antibody Reactivity following Oral Vaccination and Experimental Challenge
Authors: Ndungo Esther , Randall Arlo , Hazen Tracy H. , Kania Dane A. , Trappl-Kimmons Krista , Liang Xiaowu , Barry Eileen M. , Kotloff Karen L. , Chakraborty Subhra , Mani Sachin , Rasko David A. , Pasetti Marcela F.
Published: July 2018

Each year, more than 180 million cases of severe diarrhea caused by
Shigella
occur globally. Those affected (mostly children in poor regions) experience long-term sequelae that severely impair quality of life. Without a licensed vaccine, the burden of disease represents a daunting challenge. An improved understanding of immune responses to
Shigella
is necessary to support ongoing efforts to identify a safe and effective vaccine. We developed a microarray containing >2,000 proteins common to all
Shigella
species. Using sera from human adults who received a killed whole-cell or live attenuated vaccine or were experimentally challenged with virulent organisms, we identified new immune-reactive antigens and defined a T3SS protein signature associated with clinical protection.
Multiple Evolutionarily Conserved Domains of Cap2 Are Required for Promoter Recruitment and Iron Homeostasis Gene Regulation
Authors: Srivastav Manjit Kumar , Agarwal Neha , Natarajan Krishnamurthy
Published: July 2018

Iron is an essential micronutrient for living cells.
Candida albicans
, the predominant human fungal pathogen, thrives under diverse environments with vastly different iron levels in the mammalian host. Therefore, to tightly control iron homeostasis,
C. albicans
has evolved a set of transcriptional regulators that cooperate to either upregulate or downregulate transcription of iron uptake genes or iron utilization genes. Cap2/Hap43, a critical transcriptional regulator, contains multiple conserved protein domains. In this study, we carried out mutational analyses to identify the functional roles of the conserved protein domains in Cap2. Our results show that the bZIP, HAP4L, and the C-terminal domain are each required for Cap2 transcriptional activity. Thus, Cap2 employs multiple, disparate protein domains for regulation of iron homeostasis in
C. albicans
.
Within the limits of the defensible: a response to Simkulet’s argument against the pro-life view on the basis of spontaneous abortion
Authors: Friberg-Fernros Henrik
Published: July 2018

In a recent article, William Simkulet has argued against the anti-abortion view by invoking the fact that many human fetuses die from spontaneous abortion. He argues that this fact poses a dilemma for proponents of the anti-abortion view: either they must abandon their anti-abortion view or they must engage in preventing spontaneous abortion significantly more than at present—either to the extent that they try to prevent induced abortion or at least significantly more than they do today. In this reply, I acknowledge that, if the latter would follow, the anti-abortionist view would imply implausibly strong obligations. My aim with this reply is to demonstrate that anti-abortionists can hold on to their view without having implausibly strong obligations to prevent spontaneous abortion. My conclusion is that Simkulet clearly overstates his position by not sufficiently considering the differences between the act of killing versus death by natural causes and between positive and negative rights.
Estimating basin-wide air temperature by partial integration of remote sensing data
Authors: Ivezic Vedran , Bekic Damir , Kerin Igor
Published: July 2018

A comparison of various methods that enable temporally continuous computation of basin-wide air temperature is presented. An approach that combines remote sensing data with measurements at meteorological stations for obtaining basin-wide air temperature is proposed and compared to the standard interpolation methods of point measurements. For a basin of over 1000 km2, the proposed approach provides significantly more reliable air temperature rasters (average Δ = 9%) than the standard interpolation methods (average Δ = 25%), all by using satellite images and measurements from only two meteorological stations in comparison to standard methods using measurements from 10 meteorological stations.
Geological interpretation of the northern flank of the Matagami camp, Quebec, using gravity and magnetic inversions
Authors: Astic Thibaut , Chouteau Michel
Published: July 2018

The northern flank of the Galine anticline of the Matagami camp has been well known for decades for hosting polymetallic VMS deposits (mostly copper and zinc). In such an already explored area, sophisticated exploration tools must be used in the hope of generating new information. By integrating geophysical, petrophysical, and geological data into a three-dimensional (3D) common earth model to constrain gravity and magnetic inversions, our objective was to validate and improve the geological interpretations of the area and to highlight geophysical anomalies unexplained in the current geological model. Both 3D magnetic and gravity data inversions confirm the surface geometry and the steep dip of the geological units. The inverted gravity models indicate that units observable at the surface of the northern flank extend subvertically to several kilometres in depth. The pyroxenitic phase of the Bell River Complex is most certainly dipping steeply to the south, contrary to some surface measurements. The Olga pluton shows no significant decrease in width at depth, with the exception of the west end, which appears to be an apophysis. A major unknown mass, which may correspond to a synvolcanic mafic intrusion that is not outcropping, is revealed in the Allard River volcanic rocks. This improved geophysical model featuring geometrical constraints obtained by careful processing and inversion of the potential-fields data could contribute to new exploration targets.