bluuebunny/crossref_metadata_2025 huggingface dataset:
The process of incorporating insulin pumps into the everyday lives of people with Type 1 diabetes: A critical interpretive synthesis
Authors: Reidy Claire , Bracher Mike , Foster Claire , Vassilev Ivaylo , Rogers Anne
Published: February 2018

Background

Insulin pump therapy (IPT) is a technological advancement that has been developed to help people manage Type 1 diabetes (T1D). However, ways of managing diabetes requiring the implementation of health technologies bring new complexities and a need to understand the factors which enable people with T1D to incorporate a novel device. This new comprehension could provide an exemplar for people with long‐term conditions to incorporate new technologies more generally.

Objective

To determine what influences the incorporation, adaptation and use of IPT into the everyday lives of people living with diabetes.

Design

Critical interpretive synthesis (CIS) using systematic searches undertaken in 7 electronic databases of literature, published 2008 onwards.

Results

A total of 4998 titles were identified, 274 abstracts reviewed, 39 full articles retrieved and 22 papers selected for analysis. Three themes emerged which were of relevance to the introduction and use of IPT; Tensions between expectations and experiences in adoption and early adaptation; Negotiation of responsibility and accessing support; Reflexivity, active experimentation and feedback.

Conclusions

This CIS builds on earlier reviews on lived experiences of IPT. Novel insights are offered through examination of the experiences of pump users from children through to adults, their families and health‐care professionals. Expectations of what the device can do to improve self‐management impacts on the early stages of adoption as the reality of the technology requires substantial thought and action. Areas for intervention to improve IPT incorporation include establishing who is responsible for management tasks of the device and enabling navigation to further means of support and resources.
Preparing researchers for patient and public involvement in scientific research: Development of a hands‐on learning approach through action research
Authors: de Wit Maarten , Beurskens Anna , Piškur Barbara , Stoffers Esther , Moser Albine
Published: February 2018

Background

Acquiring the theoretical and practical knowhow of conducting patient and public involvement (PPI) in research is not part of the traditional curriculum of researchers. Zuyd University of Applied Sciences and Huis voor de Zorg, a regional umbrella patient organization, therefore started a 1.5‐year coaching programme.

Objective

To establish a community of practice by developing a PPI coaching programme for senior and junior health services researchers of Zuyd University. The context consisted of research projects conducted by the participants.

Methods

A participatory action research methodology. Data were collected from reports of thematic group meetings and individual sessions with participants, field notes and regular reflection meetings with the project team. Data were analysed by reflexive deliberation.

Findings

The programme comprised a kick‐off meeting (52 attendees), followed by 7 group meetings with 11 junior and 9 senior researchers. The project team constructed a serious game based on the concept of the participation ladder. Questions and concerns differed for junior and senior researchers, and separate tailored meetings were organized for both groups. Between group meetings, participants received individual assignments. Group meetings were accompanied by individual coaching sessions to provide tailor‐made feedback. The programme concluded with a combined meeting with all stakeholders.

Conclusion

Building a community of PPI practice through action research facilitates the development of a coaching programme that fosters social learning, empowerment and the development of a shared identity concerning PPI. The role and responsibilities of senior researchers should be distinguished from those of junior researchers.
The effect of Al2O3 on the high‐temperature oxidation resistance of Si‐B‐C ceramic under air atmosphere
Authors: Shan Qingliang , Hu Jianbao , Kan Yanmei , Ni Dewei , Gao Le , Chen Xiaowu , Dong Shaoming
Published: February 2018

Si‐B‐C ceramics were prepared through reaction sintering, and the influence of Al2O3 addition on the high‐temperature (1100‐1300°C) oxidation behavior of the material under air atmosphere was studied. The erosion behavior and mechanism are determined from the measurement of weigh changes, microstructure observations, and characterization of the generated oxides on postexposure specimens. Results show that Al2O3 is enriched in the oxidized layer, inhibiting the volatilization of B2O3 and impeding the crystallization ability of oxide (cristobalite). Narrower erosion layer and less weigh change are observed with Al2O3. Low‐frequency Raman results reveals that with the increase in Al2O3, the bending vibrations of the BO4 units and B‐O‐B stretching of the metaborate ring relative intensity are enhanced. Furthermore, high‐frequency Raman results shows that the relative proportion of high‐dimensional vibration modes Q3 and Q4 which result in a higher viscosity of melt and a greater resistance of oxygen diffusion are positively correlated with Al2O3.
Treatment efficacy of probiotics on atopic dermatitis, zooming in on infants: a systematic review and meta‐analysis
Authors: Zhao Mutong , Shen Chunping , Ma Lin
Published: February 2018

Probiotic treatment of atopic dermatitis is widely studied with controversial results. The objective of this study is to review the efficacy of probiotics for the treatment of atopic dermatitis in infants. PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, and reference lists were searched up to July 2017. Double‐blinded randomized clinical trials were included. The primary outcome was the Scoring Atopic Dermatitis index. Subgroups analyses were conducted on probiotic species, treatment duration, participant age, and disease severity. Eight clinical trials (741 infants) were included in the quantitative synthesis. The overall pooled change in Scoring Atopic Dermatitis index (95% CI) in infants was −5.71 (−8.37, −3.04), P < 0.01. Subgroup analysis revealed that the effect was protective in moderate‐to‐severe patients −8.32 (−16.35, −0.28), with preparations containing Lactobacillus −5.76 (−9.21, −2.30). Probiotics for the treatment of infantile atopic dermatitis is beneficial.
Fabrication and properties of in situ reduced graphene oxide‐toughened zirconia composite ceramics
Authors: Zeng Zhaoyubo , Liu Yunzhong , Chen Weiping , Li Xiaoqiang , Zheng Qifan , Li Kaili , Guo Ruiran
Published: February 2018

Graphene oxide and zirconia powders were mixed using a colloidal coating route. In situ reduced graphene oxide‐toughened zirconia ceramics were prepared by spark plasma sintering. Their microstructure, mechanical properties, and toughening mechanisms were investigated. The results show that graphene oxide can be easily reduced in situ during sintering and that it disperses homogeneously within the zirconia substrate. Compared with the toughness of 3 mol.% yttria‐stabilized zirconia, the fracture toughness of in situ reduced graphene oxide‐toughened zirconia increased by up to 175% (from ~6.07 to ~10.64MPa·m1/2) at 0.09 wt.% graphene oxide with a small increase in hardness. The improvement is more significant than that of prereduced graphene oxide‐toughened cases, and it is associated with the formation of a C‐O‐Zr bond at the interface in addition to conventional toughening mechanisms.
Variation in the diagnosis and clinical management of lentigo maligna across Europe: a survey study among European Association of Dermatologists and Venereologists members
Authors: Tio D. , Prinsen C.A.C. , Dréno B. , Hoekzema R. , Augustin M. , van Montfrans C.
Published: February 2018

Background

Lentigo maligna (LM), a form of melanoma in situ, is treated to prevent progression to lentigo maligna melanoma (LMM). Surgical treatment is the gold standard. However, treatment guidelines are based on expert opinion, and comparative studies are lacking.

Objective

The objective of this study was to assess the diagnostic methods and clinical management of LM patients among European dermatologists and residents.

Methods

A survey consisting of 29 questions about diagnostic methods and treatment options used for LM patients was sent to 3308 members of the European Association of Dermatologists and Venereologists (EADV).

Results

Most questions were multiple choice, and multiple answers could be ticked per question.

A total of N = 415 (12.5%) completed surveys were included in the analyses. A combination of clinical diagnosis (65.7%), dermatoscopy (83.4%) and histopathology (88.2%) is used by most respondents to diagnose LM. Tissue for histopathological evaluation was collected most often using a single punch biopsy in 61.0%. The most common treatment for LM patients <60 years of age is surgery (97.6%). For LM patients >70 years of age, 66.8% of the respondents preferred surgical treatment. Non‐surgical options such as radiotherapy (17.0%), topical imiquimod (30.6%), watchful waiting (19.6%) or cryotherapy (20.4%) were used in this elderly group. Subanalysis showed that respondents who take into account patient preference used topical imiquimod, radiotherapy and watchful waiting more often.

Conclusion

In conclusion, the results of this survey show that there is a variance in the diagnostic methods and treatment modalities used for LM across Europe. Surgery remains the most utilized option. However, non‐surgical options, such as topical imiquimod and radiotherapy, are most often used for elderly patients. We recommend that future studies focus on patient preference and compare surgical to non‐surgical therapy.
Nurturing Nature: Exploring Ecological Self‐of‐the‐Therapist Issues
Authors: Laszloffy Tracey A. , Davis Sean D.
Published: February 2018

Much has been written about the systemic effects of families and culture on individual well‐being. Seldom discussed, however, are the systemic effects of our relationship with the larger ecological system in which all families and cultures are embedded. A case is made for the importance of nature in family therapy. Furthermore, before therapists can effectively address ecological issues in therapy, they need to address various ecological self‐of‐the‐therapist issues that will influence their clinical practice. A series of questions are asked to help guide therapists in this exploration, and practical suggestions for incorporating nature intoMFTclinical practice, training, and research are made.
Optimal Longevity Hedging Framework for Insurance Companies Considering Basis and Mispricing Risks
Authors: Yang Sharon S. , Huang Hong‐Chih , Yeh Yu‐Yun
Published: February 2018

This article studies the optimal hedging strategy to deal with longevity risk for the life insurer considering basis risk. We build up a longevity hedging framework that incorporates not only the internal natural hedging but also the external hedging by using the q‐forwards. The optimal hedging strategy is obtained by a minimizing‐variance approach that can minimize the impact of longevity risk on the insurer's profit function. To investigate the basis risk, instead of using population mortality, we adopt a unique mortality data set of annuity and life insurance policies that enable us to calibrate the multi‐population mortality dynamics for different lines of insurance policies. We consider three different hedging strategies: the natural hedging strategy, the external hedging strategy, and combining both natural hedging, and external hedging strategies. The hedge effectiveness for different hedging strategies is evaluated. In addition, the mortality forecast model based on VECM and ARIMA are used to examine the impact of basis risk on hedge effectiveness. As a result, combining both internal and external hedging strategies is the most effective way to manage longevity risk. Ignoring the basis risk will decrease the hedge effectiveness.
The characteristic function of rough Heston models
Authors: El Euch Omar , Rosenbaum Mathieu
Published: February 2018

It has been recently shown that rough volatility models, where the volatility is driven by a fractional Brownian motion with small Hurst parameter, provide very relevant dynamics in order to reproduce the behavior of both historical and implied volatilities. However, due to the non‐Markovian nature of the fractional Brownian motion, they raise new issues when it comes to derivatives pricing. Using an original link between nearly unstable Hawkes processes and fractional volatility models, we compute the characteristic function of the log‐price in rough Heston models. In the classical Heston model, the characteristic function is expressed in terms of the solution of a Riccati equation. Here, we show that rough Heston models exhibit quite a similar structure, the Riccati equation being replaced by a fractional Riccati equation.
Reductions in complexity of mitochondrial genomes in lichen‐forming fungi shed light on genome architecture of obligate symbioses
Authors: Pogoda Cloe S. , Keepers Kyle G. , Lendemer James C. , Kane Nolan C. , Tripp Erin A.
Published: February 2018

Symbioses among co‐evolving taxa are often marked by genome reductions such as a loss of protein‐coding genes in at least one of the partners as a means of reducing redundancy or intergenomic conflict. To explore this phenomenon in an iconic yet under‐studied group of obligate symbiotic organisms, mitochondrial genomes of 22 newly sequenced and annotated species of lichenized fungi were compared to 167 mitochondrial genomes of nonlichenized fungi. Our results demonstrate the first broad‐scale loss of atp9 from mitochondria of lichenized fungi. Despite key functions in mitochondrial energy production, we show that atp9 has been independently lost in three different lineages spanning 10 of the 22 studied species. A search for predicted, functional copies of atp9 among genomes of other symbionts involved in each lichen revealed the full‐length, presumably functional copies of atp9 in either the photosynthetic algal partner or in other symbiotic fungi in all 10 instances. Together, these data yield evidence of an obligate symbiotic relationship in which core genomic processes have been streamlined, likely due to co‐evolution.
Seascape genomics reveals adaptive divergence in a connected and commercially important mollusc, the greenlip abalone (Haliotis laevigata), along a longitudinal environmental gradient
Authors: Sandoval‐Castillo Jonathan , Robinson Nick A. , Hart Anthony M. , Strain Lachlan W. S. , Beheregaray Luciano B.
Published: February 2018

Populations of broadcast spawning marine organisms often have large sizes and are exposed to reduced genetic drift. Under such scenarios, strong selection associated with spatial environmental heterogeneity is expected to drive localized adaptive divergence, even in the face of connectivity. We tested this hypothesis using a seascape genomics approach in the commercially important greenlip abalone (Haliotis laevigata). We assessed how its population structure has been influenced by environmental heterogeneity along a zonal coastal boundary in southern Australia linked by strong oceanographic connectivity. Our data sets include 9,109 filtered SNPs for 371 abalones from 13 localities and environmental mapping across ~800 km. Genotype–environment association analyses and outlier tests defined 8,786 putatively neutral and 323 candidate adaptive loci. From a neutral perspective, the species is better represented by a metapopulation with very low differentiation (global FST = 0.0081) and weak isolation by distance following a stepping‐stone model. For the candidate adaptive loci, however, model‐based and model‐free approaches indicated five divergent population clusters. After controlling for spatial distance, the distribution of putatively adaptive variation was strongly correlated to selection linked to minimum sea surface temperature and oxygen concentration. Around 80 candidates were annotated to genes with functions related to high temperature and/or low oxygen tolerance, including genes that influence the resilience of abalone species found in other biogeographic regions. Our study includes a documented example about the uptake of genomic information in fisheries management and supports the hypothesis of adaptive divergence due to coastal environmental heterogeneity in a connected metapopulation of a broadcast spawner.
Functional biogeography and host specificity of bacterial communities associated with the Marine Green Alga Ulva spp.
Authors: Roth‐Schulze Alexandra J. , Pintado José , Zozaya‐Valdés Enrique , Cremades Javier , Ruiz Patricia , Kjelleberg Staffan , Thomas Torsten
Published: February 2018

Bacterial communities play an essential role for the function of marine macroalgae. Recent work has shown that bacterial communities associated with individual macroalgae possess on a local scale a functional core that is likely derived from diverse members of functional guilds. It is not known whether such functional cores also exist across large spatial scales or between closely related host species. To address this, we studied here the bacterial communities on three species of the green macroalgal genus Ulva from different geographic locations. While the taxonomic composition was too variable to describe a community core, we identified genes that were enriched across all Ulva samples as compared to the communities of the surrounding seawater. Of these core functions, 70% were consistently found and independent of the Ulva species and biogeography, while the remaining functions (~30%) are possibly involved in local or host‐specific adaptations. For each host individual, the core functions are provided by bacteria with distinct phylogenetic origin and these bacteria could constitute a global guild of Ulva‐associated bacteria. Together, our results demonstrate the presence of a stable core set of functional genes in the bacterial communities associated with closely related host species and across large biogeographies.
Recent work on reflective equilibrium and method in ethics
Authors: Tersman Folke
Published: February 2018

The idea of reflective equilibrium (IRE) remains the most popular approach to questions about method in ethics, despite the masses of criticism it has been faced with over the years. Is this due to the availability of compelling responses to the criticisms or rather to factors that are independent of its reasonableness? The aim of this paper is to provide support for the first answer. I particularly focus on the recent discussion. Some recent objections are related to general arguments against the possibility of moral knowledge, such as so‐called “evolutionary debunking arguments.” I argue that nothing that has come to light in that debate, or in the recent discussion about IRE more generally, decisively strengthens the case against it. If anything, the recent developments show that IRE deserves its present status.
Absorption Characteristics and Quantum Yields of Singlet Oxygen Generation of Thioguanosine Derivatives
Authors: Miyata Shoma , Yamada Takeshi , Isozaki Tasuku , Sugimura Hideyuki , Xu Yao–Zhong , Suzuki Tadashi
Published: February 2018

6‐Thioguanine (1a) is considered to be photochemotherapeutic due to its specific characteristics of photosensitivity to UVA light and singlet molecular oxygen generation. To extend its phototherapeutic ability, two related thioguanines, 8‐thioguanine (2a) and 6,8‐dithioguanine (3a), have been designed and explored. Since the solubility of these thioguanines in dehydrated organic solvents is too poor to study, their triacetyl‐protected ribonucleosides, that is, 2′,3′,5′‐tri‐O‐acetyl‐6‐thioguanosine (1c), 2′,3′,5′‐tri‐O‐acetyl‐8‐thioguanosine (2c) and 2′,3′,5′‐tri‐O‐acetyl‐6,8‐dithioguanosine (3c) were prepared and investigated. The absorption maxima of 1c, 2c and 3c in acetonitrile were found at longer wavelengths than that of unthiolated guanosine (4c). Especially, 3c has the longest wavelength for absorption maximum and the highest value in terms of molar absorption coefficient among all thionucleobases and thionucleosides reported. These absorption properties were also well reproduced by quantum chemical calculations. Quantum yields of singlet oxygen generation of 2c and 3c were determined by near‐infrared emission measurements to be as large as that of 1c. These results suggest that the newly synthesized thioguanosines, in particular 3c, can be further developed as a potential photosensitive agent for light‐induced therapies.
Bifunctional glycosyltransferases catalyze both extension and termination of pectic galactan oligosaccharides
Authors: Laursen Tomas , Stonebloom Solomon H. , Pidatala Venkataramana R. , Birdseye Devon S. , Clausen Mads H. , Mortimer Jenny C. , Scheller Henrik Vibe
Published: February 2018

Pectins are the most complex polysaccharides of the plant cell wall. Based on the number of methylations, acetylations and glycosidic linkages present in their structures, it is estimated that up to 67 transferase activities are involved in pectin biosynthesis. Pectic galactans constitute a major part of pectin in the form of side‐chains of rhamnogalacturonan‐I. In Arabidopsis, galactan synthase 1 (GALS1) catalyzes the addition of galactose units from UDP‐Gal to growing β‐1,4‐galactan chains. However, the mechanisms for obtaining varying degrees of polymerization remain poorly understood. In this study, we show that AtGALS1 is bifunctional, catalyzing both the transfer of galactose from UDP‐α‐d‐Gal and the transfer of an arabinopyranose from UDP‐β‐l‐Arap to galactan chains. The two substrates share a similar structure, but UDP‐α‐d‐Gal is the preferred substrate, with a 10‐fold higher affinity. Transfer of Arap to galactan prevents further addition of galactose residues, resulting in a lower degree of polymerization. We show that this dual activity occurs both in vitro and in vivo. The herein described bifunctionality of AtGALS1 may suggest that plants can produce the incredible structural diversity of polysaccharides without a dedicated glycosyltransferase for each glycosidic linkage.
Physical interactions among flavonoid enzymes in snapdragon and torenia reveal the diversity in the flavonoid metabolon organization of different plant species
Authors: Fujino Naoto , Tenma Natsuki , Waki Toshiyuki , Ito Keisuke , Komatsuzaki Yuki , Sugiyama Keigo , Yamazaki Tatsuya , Yoshida Saori , Hatayama Masayoshi , Yamashita Satoshi , Tanaka Yoshikazu , Motohashi Reiko , Denessiouk Konstantin , Takahashi Seiji , Nakayama Toru
Published: February 2018

Flavonoid metabolons (weakly‐bound multi‐enzyme complexes of flavonoid enzymes) are believed to occur in diverse plant species. However, how flavonoid enzymes are organized to form a metabolon is unknown for most plant species. We analyzed the physical interaction partnerships of the flavonoid enzymes from two lamiales plants (snapdragon and torenia) that produce flavones and anthocyanins. In snapdragon, protein–protein interaction assays using yeast and plant systems revealed the following binary interactions: flavone synthase II (FNSII)/chalcone synthase (CHS); FNSII/chalcone isomerase (CHI); FNSII/dihydroflavonol 4‐reductase (DFR); CHS/CHI; CHI/DFR; and flavonoid 3′‐hydroxylase/CHI. These results along with the subcellular localizations and membrane associations of snapdragon flavonoid enzymes suggested that FNSII serves as a component of the flavonoid metabolon tethered to the endoplasmic reticulum (ER). The observed interaction partnerships and temporal gene expression patterns of flavonoid enzymes in red snapdragon petal cells suggested the flower stage‐dependent formation of the flavonoid metabolon, which accounted for the sequential flavone and anthocyanin accumulation patterns therein. We also identified interactions between FNSII and other flavonoid enzymes in torenia, in which the co‐suppression of FNSII expression was previously reported to diminish petal anthocyanin contents. The observed physical interactions among flavonoid enzymes of these plant species provided further evidence supporting the long‐suspected organization of flavonoid metabolons as enzyme complexes tethered to the ER via cytochrome P450, and illustrated how flavonoid metabolons mediate flower coloration. Moreover, the observed interaction partnerships were distinct from those previously identified in other plant species (Arabidopsis thaliana and soybean), suggesting that the organization of flavonoid metabolons may differ among plant species.
Modeling the Inertial Torque Imbalance Within an Internal Combustion Engine: Quantifying the Equivalent Mass Approximation
Authors: Manring Noah D. , Ali Muslim
Published: February 2018

The objectives of this research are to explore the inertial-torque characteristics of an inline, internal combustion engine with connecting-rod joints that are evenly spaced about the centerline of the crankshaft, and to evaluate the goodness of a mass approximation that is customarily used in machine design textbooks. In this research, the number of pistons within the internal combustion engine is varied from 1 to 8. In order to generalize the results, the inertial-torque equations are nondimensionalized and shown to depend upon only four nondimensional groups, all related to the mass and geometry properties of the connecting rod. As shown in this research, the inertial-torque imbalance is greatest for an engine with two pistons, and that a dramatic reduction in the torque imbalance may be obtained for engine designs that use four or more pistons. It is also shown in this paper that the customary mass approximations for the connecting rod may be used to simplify the analysis for all engine designs without a significant loss of modeling accuracy.
A Reduced Complexity Model for the Compressor Power of an Automotive Turbocharger
Authors: Zeng Tao , Upadhyay Devesh , Zhu Guoming
Published: February 2018

Control-oriented models for automotive turbocharger (TC) compressors typically describe the compressor power assuming an isentropic thermodynamic process with fixed isentropic and mechanical efficiencies for power transmission between the turbine and the compressor. Although these simplifications make the control-oriented model tractable, they also introduce additional errors due to unmodeled dynamics. This is especially true for map-based approaches since the manufacture-provided maps tend to be sparse and often incomplete at the operational boundaries, especially at operational conditions with low mass flow rate and low speed. Extrapolation scheme is often used when the compressor is operated outside the mapped regions, which introduces additional errors. Furthermore, the manufacture-provided compressor maps, based on steady-flow bench tests, could be quite different from those under pulsating engine flow. In this paper, a physics-based model of compressor power is developed using Euler equations for turbomachinery, where the mass flow rate and the compressor rotational speed are used as model inputs. Two new coefficients, speed and power coefficients, are defined. As a result, this makes it possible to directly estimate the compressor power over the entire compressor operational range based on a single analytic relationship. The proposed modeling approach is validated against test data from standard TC flow bench tests, standard supercharger tests, steady-state, and certain transient engine dynamometer tests. Model validation results show that the proposed model has acceptable accuracy for model-based control design and also reduces the dimension of the parameter space typically needed to model compressor dynamics.
Neyman-Pearson classification algorithms and NP receiver operating characteristics
Authors: Tong Xin , Feng Yang , Li Jingyi Jessica
Published: February 2018

An umbrella algorithm and a graphical tool for asymmetric error control in binary classification.
Increased proteomic complexity in
Drosophila
hybrids during development
Authors: Bamberger Casimir , Martínez-Bartolomé Salvador , Montgomery Miranda , Lavallée-Adam Mathieu , Yates John R.
Published: February 2018

High plasticity of the proteome in
Drosophila
hybrids reveals an unexpected space for molecular evolution during development.
Demonstration of universal parametric entangling gates on a multi-qubit lattice
Authors: Reagor Matthew , Osborn Christopher B. , Tezak Nikolas , Staley Alexa , Prawiroatmodjo Guenevere , Scheer Michael , Alidoust Nasser , Sete Eyob A. , Didier Nicolas , da Silva Marcus P. , Acala Ezer , Angeles Joel , Bestwick Andrew , Block Maxwell , Bloom Benjamin , Bradley Adam , Bui Catvu , Caldwell Shane , Capelluto Lauren , Chilcott Rick , Cordova Jeff , Crossman Genya , Curtis Michael , Deshpande Saniya , El Bouayadi Tristan , Girshovich Daniel , Hong Sabrina , Hudson Alex , Karalekas Peter , Kuang Kat , Lenihan Michael , Manenti Riccardo , Manning Thomas , Marshall Jayss , Mohan Yuvraj , O’Brien William , Otterbach Johannes , Papageorge Alexander , Paquette Jean-Philip , Pelstring Michael , Polloreno Anthony , Rawat Vijay , Ryan Colm A. , Renzas Russ , Rubin Nick , Russel Damon , Rust Michael , Scarabelli Diego , Selvanayagam Michael , Sinclair Rodney , Smith Robert , Suska Mark , To Ting-Wai , Vahidpour Mehrnoosh , Vodrahalli Nagesh , Whyland Tyler , Yadav Kamal , Zeng William , Rigetti Chad T.
Published: February 2018

Harnessing techniques from analog signal processing, we establish a new path for large-scale quantum computation.
Tailoring optical metamaterials to tune the atom-surface Casimir-Polder interaction
Authors: Chan Eng Aik , Aljunid Syed Abdullah , Adamo Giorgio , Laliotis Athanasios , Ducloy Martial , Wilkowski David
Published: February 2018

We tailor the atom-surface Casimir-Polder interaction of cesium atoms using near-infrared surface plasmons of a metamaterial.
Structure-function covariation with nonfeeding ecological variables influences evolution of feeding specialization in Carnivora
Authors: Tseng Z. Jack , Flynn John J.
Published: February 2018

Biomechanical analyses across Carnivora indicate nondietary influences on skull shape and evolution of feeding adaptations.
Wafer-scale, layer-controlled organic single crystals for high-speed circuit operation
Authors: Yamamura Akifumi , Watanabe Shun , Uno Mayumi , Mitani Masato , Mitsui Chikahiko , Tsurumi Junto , Isahaya Nobuaki , Kanaoka Yusuke , Okamoto Toshihiro , Takeya Jun
Published: February 2018

A wafer-scale, 2D organic single-crystalline semiconductor revolutionizes near-field communication.
Who let the dogs out? The ever-present threat of autoreactive T cells
Authors: Ehlers Mario R.
Published: February 2018

Islet-reactive cytotoxic CD8
+
T cells home to the pancreas in type 1 diabetes but circulate at similar frequencies in patients and healthy controls. See the related research article by

Culina
et al
.
Determinants of Extreme β-Lactam Tolerance in the Burkholderia pseudomallei Complex
Authors: Held Kiara , Gasper Joe , Morgan Sarah , Siehnel Richard , Singh Pradeep , Manoil Colin
Published: February 2018

Slow-growing bacteria are insensitive to killing by antibiotics, a trait known as antibiotic tolerance. In this study, we characterized the genetic basis of an unusually robust β-lactam (meropenem) tolerance seen in
Burkholderia
species. We identified tolerance genes under three different slow-growth conditions by extensive transposon mutant sequencing (Tn-seq), followed by single mutant validation. There were three principal findings. First, mutations in a small number of genes reduced tolerance under multiple conditions. Most of the functions appeared to be specific to peptidoglycan synthesis and the response to its disruption by meropenem action rather than being associated with more general physiological processes. The top tolerance genes are involved in immunity toward a type VI toxin targeting peptidoglycan (BTH_I0069), peptidoglycan recycling (
ldcA
), periplasmic regulation by proteolysis (
prc
), and an envelope stress response (
rpoE
and
degS
). Second, most of the tolerance functions did not contribute to growth in the presence of meropenem (intrinsic resistance), indicating that the two traits are largely distinct. Third, orthologues of many of the top
Burkholderia thailandensis
tolerance genes were also important in
Burkholderia pseudomallei
. Overall, these studies show that the determinants of meropenem tolerance differ considerably depending on cultivation conditions, but that there are a few shared functions with strong mutant phenotypes that are important in multiple
Burkholderia
species.
Functional Role of N-Linked Glycosylation in Pseudorabies Virus Glycoprotein gH
Authors: Vallbracht Melina , Rehwaldt Sascha , Klupp Barbara G. , Mettenleiter Thomas C. , Fuchs Walter
Published: February 2018

Many viral envelope proteins are modified by asparagine (N)-linked glycosylation, which can influence their structure, physicochemical properties, intracellular transport, and function. Here, we systematically analyzed the functional relevance of N-linked glycans in the alphaherpesvirus pseudorabies virus (PrV) glycoprotein H (gH), which is an essential component of the conserved core herpesvirus fusion machinery. Upon gD-mediated receptor binding, the heterodimeric complex of gH and gL activates gB to mediate fusion of the viral envelope with the host cell membrane for viral entry. gH contains five potential N-linked glycosylation sites at positions 77, 162, 542, 604, and 627, which were inactivated by conservative mutations (asparagine to glutamine) singly or in combination. The mutated proteins were tested for correct expression and fusion activity. Additionally, the mutated gH genes were inserted into the PrV genome for analysis of function during virus infection. Our results demonstrate that all five sites are glycosylated. Inactivation of the PrV-specific N77 or the conserved N627 resulted in significantly reduced
in vitro
fusion activity, delayed penetration kinetics, and smaller virus plaques. Moreover, substitution of N627 greatly affected transport of gH in transfected cells, resulting in endoplasmic reticulum (ER) retention and reduced surface expression. In contrast, mutation of N604, which is conserved in the
Varicellovirus
genus, resulted in enhanced
in vitro
fusion activity and viral cell-to-cell spread. These results demonstrate a role of the N-glycans in proper localization and function of PrV gH. However, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles.

IMPORTANCE
Herpesvirus infection requires fusion of the viral envelope with cellular membranes, which involves the conserved fusion machinery consisting of gB and the heterodimeric gH/gL complex. The bona fide fusion protein gB depends on the presence of the gH/gL complex for activation. Viral envelope glycoproteins, such as gH, usually contain N-glycans, which can have a strong impact on their folding, transport, and functions. Here, we systematically analyzed the functional relevance of all five predicted N-linked glycosylation sites in the alphaherpesvirus pseudorabies virus (PrV) gH. Despite the fact that mutation of specific sites affected gH transport,
in vitro
fusion activity, and cell-to-cell spread and resulted in delayed penetration kinetics, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles. Thus, our results demonstrate a modulatory but nonessential role of N-glycans for gH function.
Effect of Long-Term Electroacupuncture Stimulation on Recovery of Sensorimotor Function after Peripheral Nerve Anastomosis
Authors: Zhang Mingxing , Zhang Ye , Bian Yuhong , Fu Hui , Xu Ying , Guo Yi
Published: February 2018

Background

Recently, application of electroacupuncture (EA) to stimulate nerve regeneration has become a mainstream treatment in clinical rehabilitation and related basic research, but the efficacy of long-term stimulation has not been confirmed.

Objective

To evaluate the influence of long term EA on peripheral nerve injury (PNI) from multiple angles.

Method

Twenty-four rats were divided into three groups: control, PNI and PNI+EA. In the latter two groups, PNI was modelled by transection followed by re-anastomosis of thesciatic nerve. In the PNI+EA group only, EA was delivered using a discontinuous wave with frequency 5 Hz, pulse width 2 ms, and intensity approximately 2 mA, until the affected limb was observed to twitch slightly. The treatment was given for 15 min each time, six times a week (continuously for 6 days followed by a 1-day break) for a total of 8 weeks. The effects of EA on anastomotic sciatic nerve regeneration were evaluated using the sciatic function index (SFI), mechanical withdrawal thresholds, thermo-nociceptive thresholds, conduction velocity of the sciatic nerve and bilateral gastrocnemius wet weight.

Results

From weeks 2 to 4 after modelling, the SFI recovery rate in the PNI+EA group was faster than that in the PNI group. In week 4, the SFI of the PNI+EA group was significantly higher than that of the PNI group (p<0.05). However, a significant effect of EA was no longer evident from weeks 5 to 8. There was no effect of acupuncture on anti-amyotrophy and conduction velocity of the sciatic nerve at 8 weeks after modelling. EA did not shorten the paw withdrawal threshold time, but appeared to alleviate thermo-nociceptive sensitivity.

Conclusion

Long term repeated stimulation of the same site with EA does not appear to be conducive to the functional recovery of an injured sciatic nerve in rats.
Multimorbidity and out-of-pocket expenditure on medicines: a systematic review
Authors: Sum Grace , Hone Thomas , Atun Rifat , Millett Christopher , Suhrcke Marc , Mahal Ajay , Koh Gerald Choon-Huat , Lee John Tayu
Published: February 2018

Background

Multimorbidity, the presence of two or more non-communicable diseases (NCD), is a costly and complex challenge for health systems globally. Patients with NCDs incur high levels of out-of-pocket expenditure (OOPE), often on medicines, but the literature on the association between OOPE on medicines and multimorbidity has not been examined systematically.

Methods

A systematic review was conducted via searching medical and economics databases including Ovid Medline, EMBASE, EconLit, Cochrane Library and the WHO Global Health Library from year 2000 to 2016. Study quality was assessed using Newcastle-Ottawa Scale. PROSPERO: CRD42016053538.

Findings

14 articles met inclusion criteria. Findings indicated that multimorbidity was associated with higher OOPE on medicines. When number of NCDs increased from 0 to 1, 2 and ≥3, annual OOPE on medicines increased by an average of 2.7 times, 5.2 times and 10.1 times, respectively. When number of NCDs increased from 0 to 1, 2, ≥2 and ≥3, individuals spent a median of 0.36% (IQR 0.15%–0.51%), 1.15% (IQR 0.62%–1.64%), 1.41% (IQR 0.86%–2.15%), 2.42% (IQR 2.05%–2.64%) and 2.63% (IQR 1.56%–4.13%) of mean annual household net adjusted disposable income per capita, respectively, on annual OOPE on medicines. More multimorbidities were associated with higher OOPE on medicines as a proportion of total healthcare expenditures by patients. Some evidence suggested that the elderly and low-income groups were most vulnerable to higher OOPE on medicines. With the same number of NCDs, certain combinations of NCDs yielded higher medicine OOPE. Non-adherence to medicines was a coping strategy for OOPE on medicines.

Conclusion

Multimorbidity of NCDs is increasingly costly to healthcare systems and OOPE on medicines can severely compromise financial protection and universal health coverage. It is crucial to recognise the need for better equity and financial protection, and policymakers should consider health system financial options, cost sharing policies and service patterns for those with NCD multimorbidities.
Adult psychosocial outcomes of men and women who were looked-after or adopted as children: prospective observational study
Authors: Teyhan Alison , Wijedasa Dinithi , Macleod John
Published: February 2018

Objective

To investigate whether men and women who were looked-after (in public care) or adopted as children are at increased risk of adverse psychological and social outcomes in adulthood.

Design, setting

Prospective observational study using the Avon Longitudinal Study of Parents and Children, which recruited pregnant women and their male partners in and around Bristol, UK in the early 1990s.

Participants

8775 women and 3654 men who completed questionnaires at recruitment (mean age: women 29; men 32) and 5 years later.

Exposure

Childhood public care status: looked-after; adopted; not looked-after or adopted (reference group).

Outcomes

Substance use (alcohol, cannabis, tobacco) prepregnancy and 5 years later; if ever had addiction; anxiety and depression during pregnancy and 5 years later; if ever had mental health problem; social support during pregnancy; criminal conviction.

Results

For women, 2.7% were adopted and 1.8% had been looked-after; for men, 2.4% and 1.4%, respectively. The looked-after group reported the poorest outcomes overall, but this was not a universal pattern, and there were gender differences. Smoking rates were high for both the looked-after (men 47%, women 58%) and adopted (men 44%, women 40%) groups relative to the reference group (both 28%). The looked-after group were at increased risk of a high depression score (men: 26% vs 11%, OR 2.9 (95% CI 1.5 to 5.6); women: 24% vs 9%, 3.4 (2.2 to 5.0)). A high anxiety score was reported by 10% of the reference women, compared with 26% of those looked-after (3.0 (2.0 to 4.5)) and 17% of those adopted (1.8 (1.2 to 2.6)). Looked-after men and women reported the lowest social support, while criminal convictions and addiction were highest for looked-after men. Adjustment for adult socioeconomic position generally attenuated associations for the looked-after group.

Conclusions

The needs of those who experience public care as children persist into adulthood. Health and social care providers should recognise this.
Cohort profile: ‘Centenari a Trieste’ (CaT), a study of the health status of centenarians in a small defined area of Italy
Authors: Tettamanti Mauro , Marcon Gabriella
Published: February 2018

Purpose

Centenarians, a segment of the population which some 50 years ago comprised only a few individuals, now count thousands in many countries, and demographic projections forecast that this growth will continue. The study of this new population will give us new information on extreme longevity and help prepare for their health and social needs. The aim of the Centenari a Trieste study is to describe the health and health service use by centenarians, with specific focus on cognitive status.

Participants

This is a population-based study of centenarians living in the province of Trieste (Italy), a small area with a high prevalence of centenarians and a close network of health and social services, which makes it possible to conduct a study. Consenting individuals were visited by a clinician, tested by neuropsychologists and also gave a sample of their blood. Administrative data were retrieved as well.

Findings to date

Of the 163 centenarians, 70 could be contacted and participated in the study. The main reasons for non-participation were impossibility to contact the subject (70) and death (20). Centenarians were mostly women (90%), tended to live in a nursing home (60%) and were generally severely functionally impaired (Barthel Index <50: 61%). Data from the administrative database showed that about one out of five needed hospitalisation in the preceding year and more than three out of four had at least one drug prescription.

Future plans

In 2017, we started a new wave of the study enrolling people who had just become centenarian and reassessing subjects already seen; we hope to extend this recruitment in the next years. Subjects are now examined also by cardiologists and dental specialists. We are collecting further different biological specimens to investigate new hypotheses on the cognitive function of the centenarians.
New mechanism to identify cost savings in English NHS prescribing: minimising ‘price per unit’, a cross-sectional study
Authors: Croker Richard , Walker Alex J , Bacon Seb , Curtis Helen J , French Lisa , Goldacre Ben
Published: February 2018

Background

Minimising prescription costs while maintaining quality is a core element of delivering high-value healthcare. There are various strategies to achieve savings, but almost no research to date on determining the most effective approach. We describe a new method of identifying potential savings due to large national variations in drug cost, including variation in generic drug cost, and compare these with potential savings from an established method (generic prescribing).

Methods

We used English National Health Service (NHS) Digital prescribing data, from October 2015 to September 2016. Potential cost savings were calculated by determining the price per unit (eg, pill, millilitre) for each drug and dose within each general practice. This was compared against the same cost for the practice at the lowest cost decile to determine achievable savings. We compared these price-per-unit savings to the savings possible from generic switching and determined the chemicals with the highest savings nationally. A senior pharmacist manually assessed whether a random sample of savings were practically achievable.

Results

We identified a theoretical maximum of £410 million of savings over 12 months. £273 million of these savings were for individual prescribing changes worth over £50 per practice per month (mean annual saving £33 433 per practice); this compares favourably with generic switching, where only £35 million of achievable savings were identified. The biggest savings nationally were on glucose blood testing reagents (£12 million), fluticasone propionate (£9 million) and venlafaxine (£8 million). Approximately half of all savings were deemed practically achievable.

Discussion

We have developed a new method to identify and enable large potential cost savings within NHS community prescribing. Given the current pressures on the NHS, it is vital that these potential savings are realised. Our tool enabling doctors to achieve these savings is now launched in pilot form at OpenPrescribing.net. However, savings could potentially be achieved more simply through national policy change.