bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferences for treatment among adolescents with Type 1 diabetes: a national study using a discrete choice experiment model
Authors: Forsander G. , Stallknecht S. , Samuelsson U. , Marcus C. , Bøgelund M.
Published: January 2018

Aim

To test the possibility of using a discrete choice experiment model, on a national level in adolescents with Type 1 diabetes, in order to obtain a better understanding of drivers of and barriers to diabetes self‐care.

Methods

A survey instrument was constructed and tested on a small group of the target population: adolescents aged 15 to <18 years with Type 1 diabetes. All individuals in Sweden belonging to this target group (N=2112) were then identified via the Swedish paediatric diabetes quality registry SWEDIABKIDS, and were sent an invitation to answer an online questionnaire. A valid response for the discrete choice experiment analyses was achieved from 431 individuals.

Results

The included respondents were not statistically different from non‐participants in terms of age and duration of diabetes, but more young women entered the study and the participants had (on average) a significantly lower HbA1c value than the non‐participants. Participants regarded as undesirable both non‐severe hypoglycaemic events (day and night) and hyperglycaemic events. Avoiding weight gain and even achieving weight loss were the most important aspects among female respondents, who were willing to trade off a substantial level of glycaemic control [13 mmol/mol (1.2%)] to avoid a weight gain of 3 kg. Hypothetical equipment improvements were desired.

Conclusions

The responses may provide useful indications of the aspects that the respondents would prioritize given a real‐life dilemma. For treatment effects, stratification along gender lines was important, whereas the treatment administration aspects were stratified according to treatment type because these aspects are closely related.
Does wolf presence reduce moose browsing intensity in young forest plantations?
Authors: van Beeck Calkoen Suzanne T. S. , Kuijper Dries P. J. , Sand Håkan , Singh Navinder J. , van Wieren Sip E. , Cromsigt Joris P. G. M.
Published: January 2018

Large carnivores can be a key factor in shaping their ungulate prey's behavior, which may affect lower trophic levels. While most studies on trade‐offs between food acquisition and risk avoidance by ungulate prey species have been conducted in areas with limited human impact, carnivores are now increasingly returning to highly anthropogenic landscapes. Many of these landscapes are dominated by forestry, and ungulate‐forestry conflicts are an increasing issue. The aim of this study was to test if the indirect effects of a re‐colonizing large predator, the wolf Canis lupus, results in a change in browsing intensity by moose Alces alces in young forest plantations in a boreal forest in Sweden. We selected 24 different forest plantations, with 12 located in low‐wolf and 12 in high‐wolf utilization areas. In each plantation, we measured browsing intensity, tree height, tree density, distance to the closest forest edge and we counted the number of moose pellet groups. In contrast to our predictions, wolf utilization was not the main driver of moose browsing patterns. Instead, moose browsing intensity declined with tree density and height. Separate analyses on the main tree species showed that wolf utilization had an influence, but browsing intensity was in fact higher in the high‐wolf utilization areas for three out of five tree species. This pattern seemed to be driven by a strong confounding relationship between wolf utilization, tree density and height, which were both lower in the high‐wolf utilization areas. We argue that this confounding effect is due to wolves being pushed towards the less productive parts of the landscape away from human activity centers. Therefore, we concluded that in order to better understand carnivore driven risk‐mediated effects on herbivore behavior in anthropogenic landscapes we need to better understand the complexity of human–carnivore–prey‐ecosystem interactions.
Behavioural signatures of backward planning in animals
Authors: Afsardeir Arsham , Keramati Mehdi
Published: January 2018

Goal‐directed planning in behavioural and neural sciences is theorized to involve a prospective mental simulation that, starting from the animal's current state in the environment, expands a decision tree in a forward fashion. Backward planning in the artificial intelligence literature, however, suggests that agents expand a mental tree in a backward fashion starting from a certain goal state they have in mind. Here, we show that several behavioural patterns observed in animals and humans, namely outcome‐specific Pavlovian‐to‐instrumental transfer and differential outcome effect, can be parsimoniously explained by backward planning. Our basic assumption is that the presentation of a cue that has been associated with a certain outcome triggers backward planning from that outcome state. On the basis of evidence pointing to forward and backward planning models, we discuss the possibility of brain using a bidirectional planning mechanism where forward and backward trees are expanded in parallel to achieve higher efficiency.
The role of alpha oscillations in distractor inhibition during memory retention
Authors: Schroeder Svea C. Y. , Ball Felix , Busch Niko A.
Published: January 2018

Only small amounts of visual information, as determined by the capacity of working memory, can be held in an active and accessible state. Thus, it is important to select and maintain information that is relevant while ignoring irrelevant information. However, the underlying neural mechanism of these processes has yet to be identified. One potential candidate are alpha oscillations (8–14 Hz), which have been shown to inhibit stimulus processing in perceptual tasks. During memory maintenance, alpha power increases with set size suggesting that alpha oscillations are involved either in memory maintenance or in the inhibition of task‐irrelevant information to protect relevant information from interference. The need for such a protection should increase with the amount of distracting information, but most previous studies did not show any distractors. Therefore, we directly tested whether alpha oscillations are involved in inhibition of distractors during memory maintenance. Participants memorized the orientation of one or two target lines embedded among irrelevant distractors. Distractors were either strong or weak and were present during the retention interval after which participants reported the orientation of probed targets. Computational modeling showed that performance decreased with increasing set size and stronger distraction. Alpha power in the retention interval generally increased with set size, replicating previous studies. However, here stronger distractors reduced alpha power. This finding is in clear contradistinction to previous suggestions, as alpha power decrease indicates higher neuronal excitability. Thus, our data do not support the suggested role of alpha oscillations in inhibition of distraction in working memory.
Terrestrial N cycling associated with climate and plant‐specific N preferences: a review
Authors: Zhang J. , Cai Z. , Müller C.
Published: January 2018

The dramatic increase in anthropogenic reactive nitrogen (Nr) from agricultural activities negatively affects the environment. An additional challenge is to ensure food security while at the same time keeping the environmental impact to a minimum to prevent negative feedback effects on climate. To date, however, few studies have addressed the direct connection between soil N transformations, forms of N, species‐specific N preferences and climate, despite the fact that the fate of N and soil N biochemical cycling are known to be intimately linked. In this paper we review the connections between soil N transformation, species‐specific N preferences and climate, and explore how N‐use efficiency may be enhanced while minimizing the environmental effect. Gross rates of N mineralization and immobilization govern the amount of available N in soil, especially in natural ecosystems, while nitrification plays a central role in regulating the NO3− to NH4+ ratio. Plant species prefer either NH4+‐N or NO3−‐N, depending on the NO3−‐N to NH4+‐N ratio in their habitat. Thus, plant N uptake could be optimized (i.e. Nr losses reduced) if species‐specific N preferences are maintained by matching N sources applied with prevailing soil‐specific N transformations. Therefore, whether N management practices can optimize N‐use efficiencies hinges on the coupling of soil N transformation with climate and species‐specific N preferences.

Highlights

We review the inherent connections between the soil N cycle, plant N preference and climate.

Nitrification plays a central role in regulating the NO3− to NH4+ ratio in soil and soil solution.

Soil N transformations regulate the composition of hydrological N export.

Plant N uptake can be optimized if soil N cycle is well matched with plant N preference.
Genomewide evidence of environmentally mediated secondary contact of European green crab (Carcinus maenas) lineages in eastern North America
Authors: Jeffery Nicholas W. , Bradbury Ian R. , Stanley Ryan R. E. , Wringe Brendan F. , Van Wyngaarden Mallory , Lowen J. Ben , McKenzie Cynthia H. , Matheson Kyle , Sargent Philip S. , DiBacco Claudio
Published: January 2018

Genetic‐environment associations are increasingly revealed through population genomic data and can occur through a number of processes, including secondary contact, divergent natural selection, or isolation by distance. Here, we investigate the influence of the environment, including seasonal temperature and salinity, on the population structure of the invasive European green crab (Carcinus maenas) in eastern North America. Green crab populations in eastern North America are associated with two independent invasions, previously shown to consist of distinct northern and southern ecotypes, with a contact zone in southern Nova Scotia, Canada. Using aRAD‐seq panel of 9,137 genomewideSNPs, we detected 41SNPs (0.49%) whose allele frequencies were highly correlated with environmental data. A principal components analysis of 25 environmental variables differentiated populations into northern, southern, and admixed sites in concordance with the observed genomic spatial structure. Furthermore, a spatial principal components analysis conducted on genomic and geographic data revealed a high degree of global structure (p < .0001) partitioning a northern and southern ecotype. Redundancy and partial redundancy analyses revealed that among the environmental variables tested, winter sea surface temperature had the strongest association with spatial structuring, suggesting that it is an important factor defining range and expansion limits of each ecotype. Understanding environmental thresholds associated with intraspecific diversity will facilitate the ability to manage current and predict future distributions of this aquatic invasive species.
Homeobox transcription factor DLX4 is not necessary for skin development and homeostasis
Authors: Bhattacharya Shreya , Duverger Olivier , Brooks Stephen R. , Morasso Maria I.
Published: January 2018

Dlx4 is a member of a family of homeobox genes with homology to Drosophila distal‐less (dll) gene. We show that Dlx4 expression pattern partially overlaps with its cis‐linked gene Dlx3 during mouse development as well as in neonatal and adult skin. In mice, Dlx4 is expressed in the branchial arches, embryonic limbs, digits, nose, hair follicle and in the basal and suprabasal layers of mouse interfollicular epidermis. We show that inactivation of Dlx4 in mice did not result in any overtly gross pathology. Skin development, homeostasis and response to TPA treatment were similar in mice with loss of Dlx4 compared to wild‐type counterparts.
Creating the Perfect Human Race: How Far Will We Go for Designer Families?
Authors: Fenech Lisa
Published: January 2018

Genetic modifications in humans is a fast‐advancing field of science, with very little legal regulation. Scientists recently have developed a technique, clustered regularly interspaced palindromic repeat (CRISPR), which will forever change this field. Before CRISPR, all methods were too expensive and time consuming to facilitate editing human genes. CRISPR is faster and cheaper, making it a very real possibility for all. Since the discovery of CRISPR, research on human embryos has begun, with a success rate showing that creating a genetically perfect family is very real. In 2015, all federal funding for human genome modifications was banned, leaving little federal control. This Note proposes a model statute that allows for research while providing restrictions to prevent harm.
Validation and standardization of the Brazilian version of the Medication Regimen Complexity Index for older adults in primary care
Authors: Pantuzza Laís LN , Ceccato Maria das Graças B , Silveira Micheline R , Pinto Isabela VL , Reis Adriano Max M
Published: January 2018

Aim

To validate and standardize the Brazilian version of the Medication Regimen Complexity Index (MRCI) for older adults in primary healthcare.

Methods

A cross‐sectional methodological study was carried out with elderly patients attending primary healthcare centers in southeastern Brazil. Convergent validity was tested by correlating MRCI scores with medication number. Divergent validity was tested by correlating MRCI scores with age, sex, cognition, and basic and instrumental activities of daily living. Reliability was assessed by interrater and test–retest reliability. Regarding standardization, percentiles were calculated for the total MRCI scores.

Results

A total of 227 older adults were included, with a mean age of 71.4 years (standard deviation 7.5 years) and mostly women (70.9%). There was a correlation between MRCI scores and medication number (rho = 0.890; P = 0.000). There was no correlation between MRCI scores and age (P = 0.192), sex (P = 0.052), cognition (P = 0.369), and basic (P = 0.682) and instrumental (P = 0.582) activities of daily living. High interrater (intraclass correlation coefficient = 0.98; rho = 0.991) and test–retest (intraclass correlation coefficient = 0.996; rho = 0.985) reliability was obtained. The following complexity was considered: low, MRCI ≤ 9.0 points; average 0.9 < MRCI ≤ 16.5 points; and high, MRCI > 16.5 points.

Conclusions

MRCI showed satisfactory psychometric qualities for measuring regimen complexity of older adults attending the primary healthcare centers evaluated. Standardization might increase the applicability of MRCI to the health research context. Geriatr Gerontol Int 2018; 18: 853–859
An outbreak of acute hepatitis A among young adult men: clinical features and HIV coinfection rate from a large teaching hospital in Rome, Italy
Authors: Ciccullo A , Gagliardini R , Baldin G , Borghetti A , Moschese D , Emiliozzi A , Lombardi F , Ricci R , Speziale D , Pallavicini F , Di Giambenedetto S
Published: January 2018

Objectives

Italy is a low‐incidence region for hepatitis A; however, during the last 2 years an increase in the incidence of hepatitis A virus (HAV) infection was reported in Europe. The aim of this study was to describe this recent outbreak.

Methods

We retrospectively analysed all cases of acute hepatitis A diagnosed at our laboratory between January 2010 and June 2017. We evaluated the following variables at the time of diagnosis: sex, age, nationality, glutamic oxaloacetic transaminase (GOT/AST), glutamic pyruvic transaminase (GPT/ALT), bilirubin concentration, international normalized ratio (INR) and the presence or absence of anti‐HIV‐1/2 antibodies. Hospitalization was also considered. We analysed these parameters using the χ2 test and Mann–Whitney U‐test.

Results

A total of 225 cases were analysed; 82.7% were in male patients, 94.2% were in Italians and the median age of the patients was 36.4 years. At diagnosis, the median GOT value was 306 U/L, the median GPT was 1389 U/L, and the median total bilirubin value was 5.88 mg/dL. Hospitalization was required for 142 patients, with a median duration of hospital stay of 8.5 days. In 2016‐2017 we registered 141 cases, with a higher prevalence of male patients, higher GPT values and a higher prevalence of patients aged 20‐39 years compared with older (2010‐2015) cases. Homosexual intercourse was reported as the HAV risk factor in 70.2% of patients. HIV serology was available for 120 patients: 24 were HIV‐positive, four of whom represented new diagnoses. HIV‐positive patients showed lower bilirubin and GPT values and fewer hospitalizations than HIV‐negative patients.

Conclusions

In 2016–2017, we saw a rise in the number of hepatitis A cases, with a higher prevalence of adult male patients. No significant differences regarding the prevalence of HIV coinfection emerged.
Mental health assessment: Inference, explanation, and coherence
Authors: Thagard Paul , Larocque Laurette
Published: January 2018

Mental health professionals such as psychiatrists and psychotherapists assess their patients by identifying disorders that explain their symptoms. This assessment requires an inference to the best explanation that compares different disorders with respect to how well they explain the available evidence. Such comparisons are captured by the theory of explanatory coherence that states 7 principles for evaluating competing hypotheses in the light of evidence. The computational model ECHO shows how explanatory coherence can be efficiently computed. We show the applicability of explanatory coherence to mental health assessment by modelling a case of psychiatric interviewing and a case of psychotherapeutic evaluation. We argue that this approach is more plausible than Bayesian inference and hermeneutic interpretation.
Mother–Grandmother and Mother–Father Coparenting Across Time Among Mexican‐Origin Adolescent Mothers and Their Families
Authors: Derlan Chelsea L. , Umaña‐Taylor Adriana J. , Updegraff Kimberly A. , Jahromi Laudan B.
Published: January 2018

The current study examined mothers' reports of coparenting relationship dynamics (i.e., conflict, communication) within and between mother–father and mother–grandmother subsystems from 10 months postpartum to 5 years postpartum among 178 Mexican‐origin teen mothers (M age = 16.78 years; SD = 1.00). Within subsystems, more frequent mother–father coparenting conflict was associated with less frequent mother–father coparenting communication from 10 months to 5 years postpartum, and more frequent mother–father coparenting communication was associated with less frequent mother–father conflict from 3 to 4 years postpartum. Furthermore, more frequent mother–grandmother coparenting communication was associated with less frequent mother–grandmother conflict from 10 months to 2 years postpartum. Regarding relations across subsystems, more frequent mother–father coparenting conflict was associated with more frequent mother–grandmother conflict from 10 months to 2 years postpartum, as well as from 3 to 4 years postpartum. Findings have implications for future interventions focused on coparenting relationships within the context of adolescent parenthood.
Management of Challenging Esthetic Anterior Cases with Limited Restorative Space: A Clinical Report
Authors: Afify Ahmed , Haney Stephan
Published: January 2018

With careful restorative planning and surgical placement, dental implants can be used to support and retain a wide range of esthetic prostheses. When implant planning or surgical executions are less than ideal, however, the resulting restorative space can be a significant obstacle to successful treatment. The aim of this article is to describe the use of a customized anterior bar to support a partial overdenture prosthesis for a youthful patient with a high smile line and a limited restorative space of 6 mm. Details of the treatment and an illustration of the customized design are also presented.
Review: Vascular dementia: clinicopathologic and genetic considerations
Authors: Vinters H. V. , Zarow C. , Borys E. , Whitman J. D. , Tung S. , Ellis W. G. , Zheng L. , Chui H. C.
Published: January 2018

The incidence and severity of cerebrovascular disease (CVD) increase with advancing age, as does the risk of developing Alzheimer's disease (AD). Not surprisingly, heterogeneous forms ofCVDmay coexist withADchanges in the ‘ageing brain’. These include angiopathies (affecting both large and small arteries) that result from ‘classical’ risk factors (hypertension, smoking and diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely linked toAD. The morphologic consequences of these various vascular diseases are infarcts and/or haemorrhages of varying sizes within the brain, which lead to neurocognitive decline that may mimicAD– though the vascular abnormalities are usually detectable by neuroimaging. More subtle effects ofCVDmay include neuroinflammation and biochemical ‘lesions’ that have no reliable morphologic correlate and thus escape the attention of even an experienced Neuropathologist. The pathogenesis of hippocampal injury resembling ischaemic change – commonly seen in the brains of geriatric subjects – remains controversial. In recent years, genetically determined forms of microangiopathy (e.g.CADASIL,CARASIL,Trex1‐related microangiopathies,CARASAL, familial forms of cerebral amyloid angiopathy orCAA) have provided interesting cellular and molecular clues to the pathogenesis ofsporadicmicrovascular disease such as arteriolosclerosis andAD‐relatedCAA.
Epothilone D accelerates disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis
Authors: Clark J. A. , Blizzard C. A. , Breslin M. C. , Yeaman E. J. , Lee K. M. , Chuckowree J. A. , Dickson T. C.
Published: January 2018

Aims

Degeneration of the distal neuromuscular circuitry is a hallmark pathology of Amyotrophic Lateral Sclerosis (ALS). The potential for microtubule dysfunction to be a critical pathophysiological mechanism in the destruction of this circuitry is increasingly being appreciated. Stabilization of microtubules to improve neuronal integrity and pathology has been shown to be a particularly favourable approach in other neurodegenerative diseases. We present evidence here that treatment with the microtubule‐targeting compound Epothilone D (EpoD) both positively and negatively affects the spinal neuromuscular circuitry in the SOD1G93A mouse model of ALS.

Methods

SOD1G93A mice were treated every 5 days with 2 mg/kg EpoD. Evaluation of motor behaviour, neurological phenotype and survival was completed, with age‐dependent histological characterization also conducted, using the thy1‐YFP mouse. Motor neuron degeneration, axonal integrity, neuromuscular junction (NMJ) health and gliosis were also assessed.

Results

EpoD treatment prevented loss of the spinal motor neuron soma, and distal axon degeneration, early in the disease course. This, however, was not associated with protection of the NMJ synapse and did not improve motor phenotype or clinical progression. EpoD administration was also found to be neurotoxic at later disease stages. This was evidenced by accelerated motor neuron cell body loss, increasing gliosis, and was associated with detrimental outcomes to motor behaviour, clinical assessment and survival.

Conclusions

The results suggest that EpoD accelerates disease progression in the SOD1G93A mouse model of ALS, and highlights that the pathophysiological involvement of microtubules in ALS is an evolving and underappreciated phenomenon.
Phytophthora oleae sp. nov. causing fruit rot of olive in southern Italy
Authors: Ruano‐Rosa D. , Schena L. , Agosteo G. E. , Magnano di San Lio G. , Cacciola S. O.
Published: January 2018

A homothallic Phytophthora species was found to be consistently associated with a rot of mature fruits of two local cultivars of olive (Olea europaea) in Calabria, southern Italy. The phylogenetic analysis of sequences of the ITS1‐5.8S‐ITS2 region and cox1 gene enabled its identification as a new species of clade 2, with a basal position compared to previously described subclades. The new species is described formally with the epithet Phytophthora oleae, referring to the natural matrix from which it was isolated. A unique combination of molecular and morphological characters clearly separates P. oleae from other already described Phytophthora species. This new species produced semipapillate, occasionally bipapillate, persistent sporangia on simple sympodially branching sporangiophores as well as globose and smooth‐walled oogonia, paragynous antheridia and spherical, plerotic oospores. The pathogenicity of P. oleae was confirmed in inoculation trials on fruits of three olive cultivars, including the two local cultivars from which the pathogen had been isolated.
Hyperpycnal delivery of sand to the continental shelf: Insights from the Jurassic Lajas Formation, Neuquén Basin, Argentina
Authors: Steel Elisabeth , Simms Alexander R. , Steel Ronald , Olariu Cornel
Published: January 2018

Hyperpycnal currents are river‐derived turbidity currents capable of transporting significant volumes of sediment from the shoreline onto the shelf and potentially further to deep ocean basins. However, their capacity to deposit sand bodies on the continental shelf is poorly understood. Shelf hyperpycnites remain an overlooked depositional element in source to sink systems, primarily due to their limited recognition in the rock record. Recent discoveries of modern shelf hyperpycnites, and previous work describing hyperpycnites deposited in slope or deep‐water settings, provide a valuable framework for understanding and recognizing shelf hyperpycnites in the rock record. This article describes well‐sorted lobate sand bodies on the continental shelf of the Neuquén Basin, Argentina, interpreted to have been deposited by hyperpycnal currents. These hyperpycnites of the Jurassic Lajas Formation are characterized by well‐sorted, medium‐grained, parallel‐laminated sandstones with hundreds of metre extensive, decimetre thick beds encased by organic‐rich, thinly laminated sandstone and siltstone. These deposits represent slightly obliquely‐migrating sand lobes fed by small rivers and deposited on the continental shelf. Hyperpycnites of the Lajas Formation highlight several unique characteristics of hyperpycnal deposits, including their distinctively thick horizontal laminae attributed to pulsing of the hyperpycnal currents, the extraction of coarse gravel due to low flow competence, and the extraction of mud due to lofting of light interstitial fluid. Recognition of shelf hyperpycnites in the Lajas Formation of the Neuquén Basin allows for a broader understanding of shelf processes and adds to the developing facies models of hyperpycnites. Recognizing and understanding the geometry and internal architecture of shelf hyperpycnites will improve current understanding of sediment transfer from rivers to deeper water, will improve palaeoenvironmental interpretations of sediment gravity‐flow deposits, and has implications for modelling potentially high‐quality hydrocarbon reservoirs.
Characterization of the novel HLA‐B*07:305 allele by sequencing‐based typing
Authors: Guidicelli G. , Elsermans V. , Top I. , Ralazamahaleo M. , Visentin J.
Published: January 2018

HLA‐B*07:305 differs from HLA‐B*07:02:01:01 by one nucleotide substitution at position 255.
Characterization of the novel HLA allele: B*14:58
Authors: Ingrassia F. , Mistretta S. , Bavetta R. , Vega M. I. , Cappuzzo V.
Published: January 2018

HLA‐B*14:58 differs from B*14:02:01 by a polymorphism at position 506 a C instead a G.
Checkpoint molecule expression by B and T cell lymphomas in dogs
Authors: Hartley G. , Elmslie R. , Dow S. , Guth A.
Published: January 2018

Immunotherapies targeting checkpoint molecule programmed cell death 1 (PD‐1) protein were shown to be effective for treatment of non‐Hodgkin lymphoma in people, but little is known about the expression of PD‐1 or its ligand PD‐L1 by canine lymphoma. Therefore, flow cytometry was used to analyse expression of PD‐1 and PD‐L1 in canine lymphoma, using fine‐needle aspirates of lymph nodes from 34 dogs with B cell lymphoma (BCL), 6 dogs with T cell lymphoma (TCL) and 11 dogs that had relapsed. Furthermore, fine‐needle aspirates were obtained from 17 healthy dogs for comparison. Lastly, the impact of chemotherapy resistance on expression of PD‐1 and PD‐L1 was assessed in vitro. These studies revealed increased expression of PD‐L1 by malignant B cells compared to normal B cells. In the case of TCL, tumour cells and normal T cells both showed low to negative expression of PD‐1 and PD‐L1. In addition, tumour infiltrating lymphocytes from both BCL and TCL had increased expression of both PD‐1 and PD‐L1 expression compared to B and T cells from lymph nodes of healthy animals. In vitro, chemotherapy‐resistant BCL and TCL cell lines exhibited increases in both PD‐1 and PD‐L1 expression, compared to non‐chemotherapy selected tumour cells. These findings indicate that canine lymphomas exhibit upregulated checkpoint molecule expression, though the impact of checkpoint molecule expression on tumour biological behaviour remains unclear.
Risk factors for recurrence of pressure ulcers after defect reconstruction
Authors: Wurzer Paul , Winter Raimund , Stemmer Sebastian O. , Ivancic Josipa , Lebo Patricia B. , Hundeshagen Gabriel , Cambiaso‐Daniel Janos , Quehenberger Franz , Kamolz Lars‐Peter , Lumenta David B.
Published: January 2018

Patients suffering from pressure ulcers remain to be a challenging task for nursing staff and doctors in the daily clinical management, putting—notably in the case of recurrences—additional strain on the constantly reduced resources in public healthcare. We aimed to assess the risk factors for the recurrence of pressure ulcers at our institution, a tertiary referral center. In this retrospective analysis of patients admitted to our division we identified risk factors for pressure ulcer recurrence. The hospital patient database search included all patients with a diagnosis of pressure ulcers of the torso and lower extremity. One hundred sixty‐three patients were diagnosed with pressure ulcers and 55 patients with 63 pressure ulcers met our inclusion criteria. The 17 recurrences (27%) had an average follow‐up of 728 days. Most presented with lesions of the ischial tuberosity (n=24). Recurrence was statistically associated with defect size (p = 0.013, Cox regression analysis), and serum albumin levels (p = 0.045, Spearman correlation), but no association was found for body mass index, bacterial profile, comorbidities, localization, previous surgery, or time‐to‐admission for reconstruction (all p > 0.05). Supported by the recent literature we identified factors like defect size to be associated with pressure ulcer recurrence, but not with time‐to admission for reconstruction or number of previous debridements. Whether laboratory values like serum albumin levels were the cause, the result or associated with pressure ulcer recurrence warrants further investigation.
Resilience Quantification for Probabilistic Design of Cyber-Physical
System Networks
Authors: Wang Yan
Published: January 2018

Cyber-physical systems (CPS) are the physical systems of which individual components have functional identities in both physical and cyber spaces. Given the vastly diversified CPS components in dynamically evolving networks, designing an open and resilient architecture with flexibility and adaptability thus is important. To enable a resilience engineering approach for systems design, quantitative measures of resilience have been proposed by researchers. Yet, domain-dependent system performance metrics are required to quantify resilience. In this paper, generic system performance metrics for CPS are proposed, which are entropy, conditional entropy, and mutual information associated with the probabilities of successful prediction and communication. A new probabilistic design framework for CPS network architecture is also proposed for resilience engineering, where several information fusion rules can be applied for data processing at the nodes. Sensitivities of metrics with respect to the probabilistic measurements are studied. Fine-grained discrete-event simulation models of communication networks are used to demonstrate the applicability of the proposed metrics.
Variable Structure Control of a Mass Spring Damper Subjected to a Unilateral Constraint: Application to Radio-Frequency MEMS Switches
Authors: Allafi Amer L. , Chahal Premjeet , Mukherjee Ranjan , Khalil Hassan K.
Published: January 2018

A feedback control strategy is presented for improving the transient response of the ubiquitous mass-spring-damper (MSD) system; the closed-loop system has a small settling time with no overshoot for a step input. This type of response is ideal for MSD systems subjected to a unilateral constraint such as radio-frequency micro-electro-mechanical-system (RF MEMS) switches, which are required to close in a short period of time without bouncing. The control strategy switches the stiffness of the MSD between its nominal value and a negative value, resulting in a hybrid dynamical system. A phase portrait analysis of the hybrid system is carried out to establish the asymptotic stability property of the equilibrium and quantify the transient response. Simulation results are presented using parameter values of a real RF MEMS switch from the literature. As compared to open-loop strategies that are currently used, the proposed feedback control strategy promises to provide comparable switch-closing times with robust performance and eliminate bouncing.
Estimation Design Using Youla Parametrization With Automotive Applications
Authors: Assadian Francis , Beckerman Alex K. , Velazquez Alcantar Jose
Published: January 2018

Youla parametrization is a well-established technique in deriving single-input single-output (SISO) and, to a lesser extent, multiple-input multiple-ouput (MIMO) controllers (Youla, D., Bongiorno, J. J., Jr., and Lu, C., 1974, “Singleloop Feedback-Stabilization of Linear Multivariable Dynamical Plants,” Automatica, 10(2), pp. 159–173). However, the utility of this methodology in estimation design, specifically in the framework of controller output observer (COO) (Ozkan, B., Margolis, D., and Pengov, M., 2008, “The Controller Output Observer: Estimation of Vehicle Tire Cornering and Normal Forces,” ASME J. Dyn. Syst., Meas., Control, 130(6), p. 061002), is not established. The fundamental question to be answered is as follows: is it possible to design a deterministic estimation technique using Youla paramertization with the same robust performance, or better, than well-established stochastic estimation techniques such as Kalman filtering? To prove this point, at this stage, a comparative analysis between Youla parametrization in estimation and Kalman filtering is performed through simulations only. In this paper, we provide an overview of Youla parametrization for both control and estimation design. We develop a deterministic SISO and MIMO Youla estimation technique in the framework of COO, and we investigate the utility of this method for two applications in the automotive domain.
In situ annealing of III1-xMnxV ferromagnetic semiconductors
Authors: Liu Xinyu , Bac Seul-Ki , Sapkota Pitambar , Gorsak Cameron , Li Xiang , Dong Sining , Lee Sanghoon , Ptasinska Sylwia , Furdyna Jacek K. , Dobrowolska Margaret
Published: January 2018

A systematic study of low temperature (LT) annealing III1-xMnxV of (Ga1-xMnxAs and Ga1-xMnxAs1-yPy) thin films in situ with different capping layers (Se, Te, or As) was carried out without exposure to the atmosphere. Experimental results show that a correct in situ annealing approach can lead to significant increases of the Curie temperature, carrier concentration, and magnetic moment, similar to the ex situ LT-annealing experiments achieved in earlier studies. Moreover, this approach allowed us to successfully deposit high-quality semiconductor layers on top of such in situ annealed films, demonstrating great potential for designing high quality III1-xMnxV-based multilayers for spintronic applications optimized by the benefits of the LT-annealing.
SILAC identifies LAD1 as a filamin-binding regulator of actin dynamics in response to EGF and a marker of aggressive breast tumors
Authors: Roth Lee , Srivastava Swati , Lindzen Moshit , Sas-Chen Aldema , Sheffer Michal , Lauriola Mattia , Enuka Yehoshua , Noronha Ashish , Mancini Maicol , Lavi Sara , Tarcic Gabi , Pines Gur , Nevo Nava , Heyman Ori , Ziv Tamar , Rueda Oscar M. , Gnocchi Davide , Pikarsky Eli , Admon Arie , Caldas Carlos , Yarden Yosef
Published: January 2018

LAD1 coordinates EGF-stimulated changes in the cytoskeleton to support aggressive phenotypes in breast cancers.
Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Infants
Authors: Shi Zhong-Ren , Chen Xing-Kai , Tian Li-Yuan , Wang Ya-Kun , Zhang Gu-Ying , Dong Lei , Jirasomprasert Totsapol , Jacqz-Aigrain Evelyne , Zhao Wei
Published: January 2018

Ceftazidime, a third-generation cephalosporin, can be used for the treatment of adults and children with infections due to susceptible bacteria. To date, the pediatric pharmacokinetic data are limited in infants, and therefore we aimed to evaluate the population pharmacokinetics of ceftazidime in infants and to define the appropriate dose to optimize ceftazidime treatment. Blood samples were collected from children treated with ceftazidime, and concentrations of the drug were quantified by high-performance liquid chromatography with UV detection (HPLC-UV). A population pharmacokinetic analysis was performed using NONMEM software
(
version 7.2.0). Fifty-one infants
(
age range, 0.1 to 2.0 years
)
were included. Sparse pharmacokinetic samples
(
n
= 90
)
were available for analysis. A one-compartment model with first-order elimination showed the best fit with the data. A covariate analysis identified that body weight and creatinine clearance (CL
CR
) were significant covariates influencing ceftazidime clearance. Monte Carlo simulation demonstrated that the currently used dosing regimen of 50 mg
/
kg twice daily was associated with a high risk of underdosing in infants. In order to reach the target of 70% of the time that the free antimicrobial drug concentration exceeds the MIC (
fT
>MIC
), 25 mg/kg every 8 h (q8h) and 50 mg/kg q8h were required for MICs of 4 and 8 mg/liter, respectively. The population pharmacokinetic characteristics of ceftazidime were evaluated in infants. An evidence-based dosing regimen was established based on simulation.
Regulation of the CRISPR-Associated Genes by Rv2837c (CnpB) via an Orn-Like Activity in Tuberculosis Complex Mycobacteria
Authors: Zhang Yang , Yang Jun , Bai Guangchun
Published: January 2018

Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated proteins (Cas) provide bacteria and archaea with adaptive immunity to specific DNA invaders.
Mycobacterium tuberculosis
encodes a type III CRISPR-Cas system that has not been experimentally explored. In this study, we found that the CRISPR-Cas systems of both
M. tuberculosis
and
Mycobacterium bovis
BCG were highly upregulated by deletion of Rv2837c (
cnpB
), which encodes a multifunctional protein that hydrolyzes cyclic di-AMP (c-di-AMP), cyclic di-GMP (c-di-GMP), and nanoRNAs (short oligonucleotides of 5 or fewer residues). By using genetic and biochemical approaches, we demonstrated that the CnpB-controlled transcriptional regulation of the CRISPR-Cas system is mediated by an Orn-like activity rather than by hydrolyzing the cyclic dinucleotides. Additionally, our results revealed that tuberculosis (TB) complex mycobacteria are functional in processing CRISPR RNAs (crRNAs), which are also more abundant in the Δ
cnpB
strain than in the parent strain. The elevated crRNA levels in the Δ
cnpB
strain could be partially reduced by expressing
Escherichia coli orn
. Our findings provide new insight into transcriptional regulation of bacterial CRISPR-Cas systems.

IMPORTANCE
Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated proteins (Cas) provide adaptive immunity to specific DNA invaders.
M. tuberculosis
encodes a type III CRISPR-Cas system that has not been experimentally explored. In this study, we first demonstrated that the CRISPR-Cas systems in tuberculosis (TB) complex mycobacteria are functional in processing CRISPR RNAs (crRNAs). We also showed that Rv2837c (CnpB) controls the expression of the CRISPR-Cas systems in TB complex mycobacteria through an oligoribonuclease (Orn)-like activity, which is very likely mediated by nanoRNA. Since little is known about regulation of CRISPR-Cas systems, our findings provide new insight into transcriptional regulation of bacterial CRISPR-Cas systems.
Accelerated induction regimens of TNF-alpha inhibitors in patients with inflammatory bowel disease: a scoping review protocol
Authors: Johnston Amy , Natarajan Sabrina , Hayes Meghan , MacDonald Erika , Shorr Risa
Published: January 2018

Introduction

Tumour necrosis factor (TNF)-alpha inhibitors are commonly used to treat inflammatory bowel disease (IBD). In patients with IBD who are unresponsive to their first induction dose, the implementation of an ‘accelerated’ induction dose schedule (doses more frequent than recommended in product monographs) is becoming increasingly common. It is unclear whether this practice results in favourable patient outcomes, such as avoidance of surgery and disease remission. As such, there is a need to identify and map the current evidence base on accelerated induction schedules of these medications in the treatment of IBD.

Methods and analysis

A scoping review will be employed to systematically identify and characterise the nature of scientific literature on accelerated induction regimens of TNF-alpha inhibitors. MEDLINE, Embase, International Pharmaceutical Abstracts and grey literature will be searched to identify relevant studies. The titles/abstracts of all records and full text of potentially relevant articles will be independently screened for inclusion by two reviewers. Data will be abstracted from included studies by one reviewer and verified for accuracy by another. The findings will be synthesised descriptively.

Ethics and dissemination

We intend to report the findings of this scoping review in a peer-reviewed journal and a scientific conference.

Trial registration

This research was registered prospectively with the Open Science Framework (https://osf.io/z7n2d/).
Wavelet analysis of particle density functions in nucleus–nucleus interactions
Authors: Manna S. K. , Haldar P. K. , Mali P. , Mukhopadhyay A. , Singh G.
Published: January 2018

A continuous wavelet analysis is performed for pattern recognition of the pseudorapidity density profile of singly charged particles produced in [Formula: see text]O+Ag/Br and [Formula: see text]S+Ag/Br interactions, each at an incident energy of [Formula: see text] GeV per nucleon in the laboratory system. The experiments are compared with a model prediction based on the ultra-relativistic quantum molecular dynamics (UrQMD). To eliminate the contribution coming from known source(s) of particle cluster formation like Bose–Einstein correlation (BEC), the UrQMD output is modified by “an algorithm that mimics the BEC as an after burner.” We observe that for both interactions particle clusters are found at same pseudorapidity locations at all scales. However, the cluster locations in the [Formula: see text]O+Ag/Br interaction are different from those found in the [Formula: see text]S+Ag/Br interaction. Significant differences between experiments and simulations are revealed in the wavelet pseudorapidity spectra that can be interpreted as the preferred pseudorapidity values and/or scales of the pseudorapidity interval at which clusters of particles are formed. The observed discrepancy between experiment and corresponding simulation should therefore be interpreted in terms of some kind of nontrivial dynamics of multiparticle production.
Free Vibration Analysis of a Nonlinearly Tapered Cone Beam by Adomian Decomposition Method
Authors: Keshmiri Alireza , Wu Nan , Wang Quan
Published: January 2018

In this paper, the free vibration of a nonlinearly tapered cone beam is analyzed based on the Euler–Bernoulli hypothesis. The characteristic/eigenvalue equation and mode shape functions of the nonlinearly tapered cone beam are derived by the Adomian decomposition method for the first time. Using a modified mathematical procedure, the natural frequencies and mode shape functions of a general nonuniform beam are analytically derived. Several numerical examples for the vibration of uniform and linearly tapered cantilever beams are presented and compared with previous results to validate the accuracy and fast convergence of the present approach. The natural frequencies and mode shapes of vibration of exponentially and trigonometrically tapered cone beams with different taper ratios are presented. The present approach enables engineers to analytically analyze tapered beams of nonuniform configurations used as various structural components in a mathematically efficient way.
Trump versus Kim Jong-un: Four Scenarios of US-North Korea Relations
Authors: PARK Hahnkyu
Published: January 2018

In the last few months, US President Donald J Trump and North Korean leader Kim Jong-un look like two locomotives on a collision course over North Korea’s nuclear and missile issue. There may be four possible scenarios for US-North Korea relations in the future. The two countries are likely to end up with negotiation either for denuclearisation or for nuclear freeze in order to resolve the North Korean nuclear problem.
Capital Market Liberalisation in China: Progress and Challenges
Authors: WAN Jing
Published: January 2018

China’s capital market has continued to open up to the world despite disruptions. In the stock market, opening up involves the Shanghai-Hong Kong and the Shenzhen-Hong Kong Stock Connect schemes. In the exchange rate market, renminbi joined the International Monetary Fund’s Special Drawing Rights basket in 2015. In July 2017, China and Hong Kong launched the “Bond Connect” programme. In the near future the focus of capital account liberalisation is likely on the bonds market.
Humans with obesity have disordered brain responses to food images during physiological hyperglycemia
Authors: Belfort-DeAguiar Renata , Seo Dongju , Lacadie Cheryl , Naik Sarita , Schmidt Christian , Lam Wai , Hwang Janice , Constable Todd , Sinha Rajita , Sherwin Robert S.
Published: January 2018

Blood glucose levels influence brain regulation of food intake. This study assessed the effect of mild physiological hyperglycemia on brain response to food cues in individuals with obesity (OB) versus normal weight individuals (NW). Brain responses in 10 OB and 10 NW nondiabetic healthy adults [body mass index: 34 (3) vs. 23 (2) kg/m2, means (SD), P < 0.0001] were measured with functional MRI (blood oxygen level-dependent contrast) in combination with a two-step normoglycemic-hyperglycemic clamp. Participants were shown food and nonfood images during normoglycemia (~95 mg/dl) and hyperglycemia (~130 mg/dl). Plasma glucose levels were comparable in both groups during the two-step clamp ( P = not significant). Insulin and leptin levels were higher in the OB group compared with NW, whereas ghrelin levels were lower (all P < 0.05). During hyperglycemia, insula activity showed a group-by-glucose level effect. When compared with normoglycemia, hyperglycemia resulted in decreased activity in the hypothalamus and putamen in response to food images ( P < 0.001) in the NW group, whereas the OB group exhibited increased activity in insula, putamen, and anterior and dorsolateral prefrontal cortex (aPFC/dlPFC; P < 0.001). These data suggest that OB, compared with NW, appears to have disruption of brain responses to food cues during hyperglycemia, with reduced insula response in NW but increased insula response in OB, an area involved in food perception and interoception. In a post hoc analysis, brain activity in obesity appears to be associated with dysregulated motivation (striatum) and inappropriate self-control (aPFC/dlPFC) to food cues during hyperglycemia. Hyperstimulation for food and insensitivity to internal homeostatic signals may favor food consumption to possibly play a role in the pathogenesis of obesity.