bluuebunny/crossref_metadata_2025 huggingface dataset:
Amiloride Analogs as ASIC1a Inhibitors
Authors: Leng Tian‐Dong , Si Hong‐Fang , Li Jun , Yang Tao , Zhu Mengyuan , Wang Binghe , Simon Roger P. , Xiong Zhi‐Gang
Published: February 2016

Background

ASIC1a, the predominant acid‐sensing ion channels (ASICs), is implicated in neurological disorders including stroke, traumatic spinal cord injury, and ALS. Potent ASIC1a inhibitors should have promising therapeutic potential for ASIC1a‐related diseases.

Aims

We examined the inhibitory effects of a number of amiloride analogs on ASIC1a currents, aimed at understanding the structure–activity relationship and identifying potent ASIC1a inhibitors for stroke intervention.

Methods

Whole‐cell patch‐clamp techniques and a mouse model of middle cerebral artery occlusion (MCAO)‐induced focal ischemia were used. Surflex‐Dock was used to dock the analogs into the pocket with default parameters.

Results

Amiloride and its analogs inhibit ASIC1a currents expressed in Chinese hamster ovary cells with a potency rank order of benzamil > phenamil > 5‐(N,N‐dimethyl)amiloride (DMA) > amiloride > 5‐(N,N‐hexamethylene)amiloride (HMA) ≥ 5‐(N‐methyl‐N‐isopropyl)amiloride (MIA) > 5‐(N‐ethyl‐N‐isopropyl)amiloride (EIPA). In addition, amiloride and its analogs inhibit ASIC currents in cortical neurons with the same potency rank order. In mice, benzamil and EIPA decreased MCAO‐induced infarct volume. Similar to its effect on the ASIC current, benzamil showed a much higher potency than EIPA.

Conclusion

Addition of a benzyl group to the terminal guanidinyl group resulted in enhanced inhibitory activity on ASIC1a. On the other hand, the bulky groups added to the 5‐amino residues slightly decreased the activity. Among the tested amiloride analogs, benzamil is the most potent ASIC1a inhibitor.
Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans
Authors: Minassian Karen , Hofstoetter Ursula S.
Published: February 2016

Severe spinal cord injury is a devastating condition, tearing apart long white matter tracts and causing paralysis and disability of body functions below the lesion. But caudal to most injuries, the majority of neurons forming the distributed propriospinal system, the localized gray matter spinal interneuronal circuitry, and spinal motoneuron populations are spared. Epidural spinal cord stimulation can gain access to this neural circuitry. This review focuses on the capability of the human lumbar spinal cord to generate stereotyped motor output underlying standing and stepping, as well as full weight‐bearing standing and rhythmic muscle activation during assisted treadmill stepping in paralyzed individuals in response to spinal cord stimulation. By enhancing the excitability state of the spinal circuitry, the stimulation can have an enabling effect upon otherwise “silent” translesional volitional motor control. Strategies for achieving functional movement in patients with severe injuries based on minimal translesional intentional control, task‐specific proprioceptive feedback, and next‐generation spinal cord stimulation systems will be reviewed. The role of spinal cord stimulation can go well beyond the immediate generation of motor output. With recently developed training paradigms, it can become a major rehabilitation approach in spinal cord injury for augmenting and steering trans‐ and sublesional plasticity for lasting therapeutic benefits.
Metonymy as Referential Dependency: Psycholinguistic and Neurolinguistic Arguments for a Unified Linguistic Treatment
Authors: Piñango Maria M. , Zhang Muye , Foster‐Hanson Emily , Negishi Michiro , Lacadie Cheryl , Constable R. Todd
Published: February 2016

We examine metonymy at psycho‐ and neurolinguistic levels, seeking to adjudicate between two possible processing implementations (one‐ vs. two‐mechanism). We compare highly conventionalized systematic metonymy (producer‐for‐product: “All freshmen read O'Connell”) to lesser‐conventionalized circumstantial metonymy (“[a waitress says to another:] ‘Table 2 asked for more coffee.”’). Whereas these two metonymy types differ in terms of contextual demands, they each reveal a similar dependency between the named and intended conceptual entities (e.g., Jackendoff, 1997; Nunberg, 1979, 1995). We reason that if each metonymy yields a distinct processing time course and substantially non‐overlapping preferential localization pattern, it would not only support a two‐mechanism view (one lexical, one pragmatic) but would suggest that conventionalization acts as a linguistic categorizer. By contrast, a similar behavior in time course and localization would support a one‐mechanism view and the inference that conventionalization acts instead as a modulator of contextual felicitousness, and that differences in interpretation introduced by conventionalization are of degree, not of kind. Results from three paradigms: self‐paced reading (SPR), event‐related potentials (ERP), and functional magnetic resonance imaging (fMRI), reveal the following: no main effect by condition (metonymy vs. matched literal control) for either metonymy type immediately after the metonymy trigger, and a main effect for only the Circumstantial metonymy one word post‐trigger (SPR); a N400 effect across metonymy types and a late positivity for Circumstantial metonymy (ERP); and a highly overlapping activation connecting the left ventrolateral prefrontal cortex and the left dorsolateral prefrontal cortex (fMRI). Altogether, the pattern observed does not reach the threshold required to justify a two‐mechanism system. Instead, the pattern is more naturally (and conservatively) understood as resulting from the implementation of a generalized referential dependency mechanism, modulated by degree of context dependence/conventionalization, thus supporting architectures of language whereby “lexical” and “pragmatic” meaning relations are encoded along a cline of contextual underspecification.
Information‐Theoretic Measures Predict the Human Judgment of Rhythm Complexity
Authors: de Fleurian Remi , Blackwell Tim , Ben‐Tal Oded , Müllensiefen Daniel
Published: February 2016

To formalize the human judgment of rhythm complexity, we used five measures from information theory and algorithmic complexity to measure the complexity of 48 artificially generated rhythmic sequences. We compared these measurements to human prediction accuracy and easiness judgments obtained from a listening experiment, in which 32 participants guessed the last beat of each sequence. We also investigated the modulating effects of musical expertise and general pattern identification ability. Entropy rate and Kolmogorov complexity were correlated with prediction accuracy, and highly correlated with easiness judgments. A logistic regression showed main effects of musical training, entropy rate, and Kolmogorov complexity, and an interaction between musical training and both entropy rate and Kolmogorov complexity. These results indicate that information‐theoretic concepts capture some salient features of the human judgment of rhythm complexity, and they confirm the influence of musical expertise on complexity judgments.
Mapping the impact of alien species on marine ecosystems: the Mediterranean Sea case study
Authors: Katsanevakis Stelios , Tempera Fernando , Teixeira Heliana
Published: February 2016

Aim

To develop a standardized, quantitative method for mapping cumulative impacts of invasive alien species on marine ecosystems.

Location

The methodology is applied in the Mediterranean Sea but is widely applicable.

Methods

A conservative additive model was developed to account for the Cumulative IMPacts of invasive ALien species (CIMPAL) on marine ecosystems. According to this model, cumulative impact scores are estimated on the basis of the distributions of invasive species and ecosystems, and both the reported magnitude of ecological impacts and the strength of such evidence. In the Mediterranean Sea case study, the magnitude of impact was estimated for every combination of 60 invasive species and 13 habitats, for every 10 × 10 km cell of the basin. Invasive species were ranked based on their contribution to the cumulative impact score across the Mediterranean.

Results

The CIMPAL index showed strong spatial heterogeneity. Spatial patterns varied depending on the pathway of initial introduction of the invasive species in the Mediterranean Sea. Species introduced by shipping gave the highest impact scores and impacted a much larger area than those introduced by aquaculture and the Suez Canal. Overall, invasive macroalgae had the highest impact among all taxonomic groups. These results represent the current best estimate of the spatial variation in impacts of invasive alien species on ecosystems, in the Mediterranean Sea.

Main Conclusions

A framework for mapping cumulative impacts of invasive alien species was developed. The application of this framework in the Mediterranean Sea provided a baseline that can be built upon with future improved information. Such analysis allows the identification of hotspots of highly impacted areas, and prioritization of sites, pathways and species for management actions.
Comparison of fetal cartilage‐derived progenitor cells isolated at different developmental stages in a rat model
Authors: Kim Mijin , Kim Jiyoung , Park So Ra , Park Do Young , Kim Young Jick , Choi Byung Hyune , Min Byoung‐Hyun
Published: February 2016

Fetal cartilage‐derived progenitor cells (FCPCs) could be a useful cell source in cell‐based therapies for cartilage disorders. However, their characteristics can vary depending on the developmental stages. The aim of this study was to compare the characteristics of rat FCPCs from the hind limb on embryonic day 14 (E14), E16 and E20 regarding proliferation, pluripotency, and differentiation. Morphologically, rat fetal cartilage tissue showed an increase in cartilaginous differentiation features (Safranin‐O, type II collagen) and decrease in pluripotency marker (Sox2) in the order of E14, E16 and E20. E14 FCPCs showed significantly higher doubling time compared to E16 and E20 FCPCs. While the E14 FCPCs expressed pluripotent genes (Sox2, Oct4, Nanog), the E16 and E20 FCPCs expressed chondrogenic markers (Sox9, Col2a1, Acan). E20 FCPCs showed the highest ability to both chondrogenic and adipogenic differentiation and E14 FCPCs showed relatively better activity in osteogenic differentiation. Further analysis showed that E20 FCPCs expressed both adipogenic (C/ebpß) and osteogenic (Runx2, Sp7, Taz) transcription factors as well as chondrogenic transcription factors. Our results show an inverse relationship overall between the expression of pluripotency genes and that of chondrogenic and lineage‐specific genes in FCPCs under development. Due to its exceptional proliferation and chondrogenic differentiation ability, fetal cells from epiphyseal cartilage (E20 in rats) may be a suitable cell source for cartilage regeneration.
Clinical characteristics and neurodevelopmental outcomes of children with tuberculous meningitis and hydrocephalus
Authors: Rohlwink Ursula K , Donald Kirsty , Gavine Bronwyn , Padayachy Llewellyn , Wilmshurst Jo M , Fieggen Graham A , Figaji Anthony A
Published: February 2016

Aim

Tuberculous meningitis (TBM) is a lethal and commonly occurring form of extra‐pulmonary tuberculosis in children, often complicated by hydrocephalus which worsens outcome. Despite high mortality and morbidity, little data on the impact on neurodevelopment exists. We examined the clinical characteristics, and clinical and neurodevelopmental outcomes of TBM and hydrocephalus.

Method

Demographic and clinical data (laboratory and radiological findings) were prospectively collected on children treated for probable and definite TBM with hydrocephalus. At 6 months, clinical outcome was assessed using the Paediatric Cerebral Performance Category Scale and neurodevelopmental outcome was assessed with the Griffiths Mental Development Scale – Extended Version.

Results

Forty‐four patients (median age 3y 3mo, range 3mo–13y 1mo, [SD 3y 5mo]) were enrolled. The mortality rate was 16%, three patients (6.8%) were in a persistent vegetative state, two were severely disabled (4.5%), and 11 (25%) suffered mild–moderate disability. All cases demonstrated neurodevelopmental deficits relative to controls. Multiple or large infarcts were prognostic of poor outcome.

Interpretation

Neurological and neurodevelopmental deficits are common after paediatric TBM with hydrocephalus, and appear to be related to ongoing cerebral ischaemia and consequent infarction. The impact of TBM on these children is multidimensional and presents short‐ and long‐term challenges.
From gene discovery to precision intervention in epilepsy: almost the end of the beginning
Authors: Pearl Phillip L
Published: February 2016

This commentary is on the case report by Papandreou et al. on pages 416–420 of this issue.
Fetal alcohol spectrum disorders are clearly brain‐based
Authors: Bertrand Jacquelyn
Published: February 2016

This commentary is on the original article by Lucas et al. on pages 861–867 of this issue.
Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon‐like peptide‐1 secretion
Authors: Hansen M. , Scheltema M. J. , Sonne D. P. , Hansen J. S. , Sperling M. , Rehfeld J. F. , Holst J. J. , Vilsbøll T. , Knop F. K.
Published: February 2016

Aim

To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic polypeptide, glucose, insulin, C‐peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake.

Methods

On four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo. At baseline and for 180 min after instillation, blood was sampled.

Results

In both the type 2 diabetes group and the healthy control group, CDCA elicited an increase in GLP‐1 levels compared with colesevelam, CDCA + colesevelam and placebo, respectively (p < 0.05). The interventions did not affect plasma glucose, insulin or C‐peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin : glucose ratio compared with colesevelam, CDCA + colesevelam and placebo in both groups. Compared with colesevelam, CDCA + colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups.

Conclusions

CDCA increased GLP‐1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid‐induced activation of TGR5 on L cells increases GLP‐1 secretion, which, in turn, may result in amplification of glucose‐stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP‐1 secretion in humans.
Switching from sulphonylurea to a sodium‐glucose cotransporter2 inhibitor in the fasting month of Ramadan is associated with a reduction in hypoglycaemia
Authors: Wan Seman W. J. , Kori N. , Rajoo S. , Othman H. , Mohd Noor N. , Wahab N. A , Sukor N. , Mustafa N. , Kamaruddin N. A.
Published: February 2016

The aim of the present study was to assess the hypoglycaemia risk and safety of dapagliflozin compared with sulphonylurea during the fasting month of Ramadan. In this 12‐week, randomized, open‐label, two‐arm parallel group study, 110 patients with type 2 diabetes who were receiving sulphonylurea and metformin were randomized either to receive 10 mg (n = 58) of dapagliflozin daily or to continue receiving sulphonylurea (n = 52). The primary outcome was to compare the effects of dapagliflozin and sulphonylurea on the proportions of patients with at least one episode of hypoglycaemia during Ramadan, as well as to assess the safety of dapagliflozin when used to treat patients observing Ramadan. A lower proportion of patients had reported or documented hypoglycaemia in the dapagliflozin group than in the sulphonylurea group: 4 (6.9%) versus 15 (28.8%); p = 0.002. The relative risk of any reported or documented hypoglycaemia in the 4th week of Ramadan was significantly lower in the dapagliflozin group: RR=0.24, 95%CI: 0.09, 0.68; p=0.002. No significance differences were observed between the two groups regarding postural hypotension (13.8 vs 3.8%; p = 0.210) or urinary tract infections (10.3 vs 3.8%; p = 0.277). In conclusion, fewer patients exhibited hypoglycaemia in the dapagliflozin group than in the sulphonylurea group.
Global test of Eltonian niche conservatism of nonnative freshwater fish species between their native and introduced ranges
Authors: Comte Lise , Cucherousset Julien , Olden Julian D.
Published: February 2016

Despite growing evidence that biotic interactions limit the distribution of species and their potential redistribution under climate change, the recent surge of interest in niche conservatism has predominantly focused on the Grinellian (abiotic) niche, whereas few studies have attempted to quantify potential lability in the Eltonian (biotic or trophic) niche. Here, we test for conservatism in the Eltonian niche of 32 freshwater fish species between their introduced and native ranges from 435 populations across the globe. We used stable isotope data to quantify niche shifts along the horizontal (δ13C: indicating the origin of the resources consumed) and vertical (δ15N: describing the trophic position) dimensions of the isotopic niche, as well as shifts in overall isotopic niche breadth. Using an assemblage centroid standardized isotope vector analysis and controlling for phylogenetic relatedness among species, we demonstrated that introduced freshwater fishes exhibited flexibility in both resource use and trophic position that was beyond levels of natural variability observed in their native ranges. By contrast, niche breadth showed variability only within the limits recorded in native populations and varied independently from shifts in mean isotopic niche positions. Across all species and introduction histories, we found a consistent shift towards more balanced acquisition of resources with mixed origins and at intermediate trophic positions, suggesting a general mechanism by which fish species successfully establish into recipient communities. The mechanisms that promote or inhibit species from shifting their Eltonian niche remains unknown, but trophic flexibility is likely to contribute to both the success and the ecological impacts of invasive species and range shifts of native species under future global change.
Opening the Black Box of Developmental Experiments: Behavioural Mechanisms Underlying Long‐Term Effects of Early Social Experience
Authors: Taborsky Barbara
Published: February 2016

Typically, animals spend a considerable portion of their time with social interactions involving mates, offspring, competitors and group members. The social performance during these interactions can strongly depend on the social environment individuals have experienced early in life. Despite a considerable number of experiments investigating long‐term effects of the early social environment, our understanding of the behavioural mechanisms mediating these effects is still limited, mainly for two reasons. (1) Only in few experimental studies have researchers actually observed and quantified the behaviour of their study animals during the social treatment. (2) Even if differences in social interactions between social rearing treatments are reported, these differences might not be causally linked to any observed long‐term effects later in life. The aim of this review was to investigate whether behavioural records of animals during the experimental manipulation of their social environment can help (1) identifying behavioural mechanisms involved in a long‐term effect and (2) obtaining a better understanding of the long‐term consequences of early manipulations. First, I review studies that manipulated the social environment at an early stage of the ontogeny, observed the social interactions and behaviour during the social experience phase and subsequently tested the performance in social and non‐social behavioural tasks at a later life stage. In all reviewed studies, treatment differences were reported both in social interactions during the social experience phase and in social and/or non‐social behaviours later in life. Second, I discuss four classes of behavioural mechanisms that can cause the reported long‐term effects of social experience, namely learning by experience, social learning, sensory stimulation and social cueing. I conclude that social interactions during the social experience phase should always be recorded for at least two reasons. Knowledge about how the social interactions differ between rearing treatments (1) permits researchers to formulate hypotheses about candidate mechanisms causing long‐term effects on behaviour and (2) can help to interpret unexpected outcomes of developmental experiments. Finally, I propose that as a crucial ultimate step towards understanding effects of the early social environment, we should develop targeted experiments testing for the causality of identified candidate mechanism.
Evaluation of a wireless activity monitoring system to quantify locomotor activity in horses in experimental settings
Authors: Fries M. , Montavon S. , Spadavecchia C. , Levionnois O. L.
Published: February 2016

Reasons for performing study

Methods of evaluating locomotor activity can be useful in efforts to quantify behavioural activity in horses objectively.

Objectives

To evaluate whether an accelerometric device would be adequate to quantify locomotor activity and step frequency in horses, and to distinguish between different levels of activity and different gaits.

Study design

Observational study in an experimental setting.

Methods

Dual‐mode (activity and step count) piezo–electric accelerometric devices were placed at each of 4 locations (head, withers, forelimb and hindlimb) in each of 6 horses performing different controlled activities including grazing, walking at different speeds, trotting and cantering. Both the activity count and step count were recorded and compared by the various activities. Statistical analyses included analysis of variance for repeated measures, receiver operating characteristic curves, Bland–Altman analysis and linear regression.

Results

The accelerometric device was able to quantify locomotor activity at each of the 4 locations investigated and to distinguish between gaits and speeds. The activity count recorded by the accelerometer placed on the hindlimb was the most accurate, displaying a clear discrimination between the different levels of activity and a linear correlation to speed. The accelerometer placed on the head was the only one to distinguish specifically grazing behaviour from standing. The accelerometer placed on the withers was unable to differentiate different gaits and activity levels. The step count function measured at the hindlimb was reliable but the count was doubled at the walk.

Conclusions

The dual‐mode accelerometric device was sufficiently accurate to quantify and compare locomotor activity in horses moving at different speeds and gaits. Positioning the device on the hindlimb allowed for the most accurate results. The step count function can be useful but must be manually corrected, especially at the walk.
Detecting signatures of competition from observational data: a combined approach using DNA barcoding, diversity partitioning and checkerboards at small spatial scales
Authors: Bringloe Trevor T. , Adamowicz Sarah J. , Harvey Vivian F. I. , Jackson John K. , Cottenie Karl
Published: February 2016

Competitive interactions are assumed to play a role in governing species distributions but are difficult to infer using observational data. In addition, morphological identification may overlook species, obscuring patterns of competitive exclusion. To address these limitations, we showcase a molecular (DNA barcoding) approach to species‐unit delineation and sample stream insect communities at small spatial scales where environmental filtering and dispersal limitations are minimised.

Rocks from riffles were sampled for stream insects, in particular caddisfly (Trichoptera), beetle (Coleoptera) and blackfly (Simuliidae) larvae from filterer and grazer guilds at White Clay Creek, Pennsylvania, U.S.A. (20 June, 2013). Additive partitioning of species diversity was used to establish at which spatial scale(s) variation in the distribution of species occurs; this informed us of the spatial scale at which to conduct checkerboard analyses, which tested for signatures of species segregations (e.g. competitive exclusion).

Only a small portion of the total species diversity occurred at the smallest spatial level (mean = 30% on individual rocks). Distributional variation in species was greatest at the kilometre scale (where beta‐diversity was 37% and 41% for filterers and grazers respectively). At the scale of White Clay Creek sampled (c. 3 km extent), species of filterers showed a strong tendency to segregate on individual rocks, while grazers showed random structure approaching aggregation.

This study demonstrates a potential approach to assessing the role of competition in structuring communities using observational data and highlights the importance of accurate species units for analysis (e.g. DNA barcoding). Using a combination of analyses, we were able to link patterns of segregation to competitive interactions among stream insect species in a filterer guild, while determining these interactions were not important in a grazer guild.
A Modest Defense of Politically Engaged Best Practices: The Case of Legislative Strengthening
Authors: Guinn David E. , Straussman Jeffrey D.
Published: February 2016

Critics of donor‐funded democracy promotion claim that these programs are frequently designed to reproduce social and governmental models drawn from developed countries and imposed on the recipient country without regard to local conditions, with experts parachuted in to provide guidance based on international “best practices.” The critique focuses on first‐generation development with a neutral, technical focus, whereas democracy promotion has evolved toward a more politically engaged approach to programming—what we label as second‐generation and, more recently, third‐generation development practices. We apply this distinction to the area of legislative strengthening (LS) by describing its history from the post–World War II period to the present and provide examples of LS projects to support the argument. The challenge is to combine valuable insights from best practices from decades of experience while adapting them through political engagement with local partners and with bilateral donors.
Patient involvement in the development of patient‐reported outcome measures: a scoping review
Authors: Wiering Bianca , de Boer Dolf , Delnoij Diana
Published: February 2016

Background

Patient‐reported outcome measures (PROMs) measure patients’ perspectives on health outcomes and are increasingly used in health care. To capture the patient's perspective, it is essential that patients are involved inPROMdevelopment

Objective

This article reviews in what ways and to what extent patients are involved inPROMdevelopment and whether patient involvement has increased over time.

Search strategy

Literature was searched inPubMed,EMBASE,MEDLINEand the Cochrane Methodology Register.

Inclusion criteria

Studies were included if they described a newPROMdevelopment.

Data extraction

Basic information and information regarding patient involvement in development phases was recorded.

Main results

A total of 189 studies, describing the development of 193PROMs, were included. MostPROMs were meant for chronic disease patients (n= 59) and measured quality of life (n= 28). In 25.9% of thePROMdevelopment studies, no patients were involved. Patients were mostly involved during item development (58.5%), closely followed by testing for comprehensibility (50.8%), while patient involvement in determining which outcome to measure was minimal (10.9%). Some patient involvement took place in the development of mostPROMs, but in only 6.7% patients were involved in all aspects of the development. Patient involvement did not increase with time.

Conclusions

Although patient involvement inPROMdevelopment is essential to develop valid patient‐centredPROMs, patients are not always involved. When patients are involved, their level of involvement varies considerably. These variations suggest that further attention to building and/or disseminating consensus on requirements for patient involvement inPROMdevelopment is necessary.
Infection‐related and ‐unrelated malignancies, HIV and the aging population
Authors: Shepherd L , Borges ÁH , Ledergerber B , Domingo P , Castagna A , Rockstroh J , Knysz B , Tomazic J , Karpov I , Kirk O , Lundgren J , Mocroft A ,   EuroSIDA in EuroCOORD
Published: February 2016

Objectives

HIV‐positive people have increased risk of infection‐related malignancies (IRMs) and infection‐unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence.

Methods

People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence.

Results

A total of 15 648 people contributed 95 033 person‐years of follow‐up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5‐year period from 3.1 (95% CI 1.5–5.9) per 1000 person‐years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person‐years over the same period.

Conclusions

Demographic and HIV‐related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV‐infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV‐infected populations.
Graduate nurses' experiences of mental health services in their first year of practice: An integrative review
Authors: Hooper Mary‐Ellen , Browne Graeme , O'Brien Anthony Paul
Published: February 2016

New graduate nurses have reported negative experiences in mental health settings, particularly during the transitional period of practice. Previous research has focused on addressing the undergraduate preparation of nurses for practice instead of the experiences and outcomes of the transitional period. Recently, there has been growing interest in exploring the experiences of graduate nurses in transition and the implementation of promising interventions to facilitate new graduates' assimilation to practice. Despite these initiatives, the overall shortage of mental health nurses continues to rise, and graduates still report negative experiences in the mental health setting. The purpose of this study was to identify and explore the experiences of new graduate nurses in mental health services in their first year of clinical practice. An integrative review was conducted with 22 studies sourced from the CINAHL, PubMed, Scopus, and PsychINFO electronic databases, as well as through hand‐searching the literature. Literature review findings have highlighted negative clinical experiences and increased attrition from mental health services for graduate nurses. These experiences were closely linked with the changes in the training of mental health nurses, role ambiguity, inadequate clinical preceptorship, encountering the reality of mental health services, and the role of health services in transitioning graduate nurses into clinical practice. Established research into organizational cultures demonstrates that negative organizational outcomes result from negative workplace experiences. Therefore, further research into new graduate nurses' experiences of mental health nursing and its culture might clarify the reasons why they might not be attracted to the discipline and/or are leaving early in their career.
‘People look down on you when you tell them how he died’: Qualitative insights into stigma as experienced by suicide survivors
Authors: Peters Kath , Cunningham Colleen , Murphy Gillian , Jackson Debra
Published: February 2016

This paper aims to present findings that convey how people felt stigmatized after the loss of a loved one to suicide. A qualitative design was used for the purpose of this study. Data were collected using in‐depth, face‐to‐face interviews. Audio‐recordings of the interviews were transcribed and thematically analyzed. Ten people bereaved by suicide participated in the study. Four themes emerged from the data namely: Feeling blamed, shamed and judged; Feeling isolated/rejected by friends and community; Feeling silenced and Feeling the burden of others' discomfort. Findings show that stigmatization of the bereaved by suicide had detrimental effects on their relationships and their help seeking behaviours. Further, due to stigma imposed on them by others, participants were denied the opportunity to tell their stories which further complicated their grieving process. Further education and training is required for health professionals to enhance understanding of the specific needs of those bereaved by suicide.
Understanding the influence of absorptive capacity and ambidexterity on the process of business model change – the case of on‐premise and cloud‐computing software
Authors: Kranz Johann J. , Hanelt André , Kolbe Lutz M.
Published: February 2016

The increasing popularity of Software as a Service has strongly affected the established business model of on‐premise enterprise software. Software as a Service has distinctive characteristics of disruptive innovations that typically create several difficulties for incumbent firms, in particular with regard to adapting business models. To date, however, little empirical understanding exists regarding the dynamics of business model change – a topic of special importance to the highly dynamic software industry, which is characterised by rapid and regular emergence of disruptive innovations. As disruptive innovations require gathering distant knowledge and experimenting with new ideas, this study addresses theoretical gaps regarding the role of absorptive capacity and organisational ambidexterity in the process of business model change owing to the emergence of a disruptive innovation. Drawing on evidence from multiple case studies of six incumbent vendors of enterprise resource‐planning software and informed by a thorough review of related secondary data, we investigate the pace and path of incumbents' business model adaptations. We propose a theoretical model that refines prior literature on absorptive capacity and organisational ambidexterity, particularly with regard to the process of business model change. This study identifies further technological factors that determine how and why incumbents change business models. In addition, our study provides in‐depth insights on the technological trajectory of enterprise resource‐planning software switching from on‐premise to on‐demand software services. © 2016 Blackwell Publishing Ltd
Towards Enhancement of Early‐Stage Chilling Tolerance and Root Development in Sorghum F1 Hybrids
Authors: Windpassinger S. , Friedt W. , Deppé I. , Werner C. , Snowdon R. , Wittkop B.
Published: February 2016

Sorghum (Sorghum bicolor L. Moench) is regarded a drought‐tolerant alternative to maize as a bioenergy and fodder crop, but its early‐stage chilling sensitivity is obstructing a successful implementation in temperate areas. While several studies have identified quantitative trait loci (QTL) underlying chilling tolerance‐related traits in sorghum lines, little is known about the inheritance of these traits in F1 hybrids. We have conducted a comprehensive approach to analyse heterosis, combining ability and the relation between line per se and hybrid performance for emergence and early shoot and root development comprising both field trials and controlled environment experiments including chilling tests. To our best knowledge, this is the first study analysing heterosis for sorghum root parameters under chilling. Our results show that most traits are heterotic and that the mid‐parent values are rather poor predictors of hybrid performance. Hybrid breeding programmes should focus on efficient GCA tests and the establishment of genetically diverse pools to maximise heterosis rather than on a too strict selection among lines based on their per se performance. The medium‐to‐high heritabilities estimated for seedling emergence and juvenile biomass suggest that a robust breeding progress for these complex traits is feasible.
Instantiating informatics in nursing practice for integrated patient centred holistic models of care: a discussion paper
Authors: Hussey Pamela A. , Kennedy Margaret Ann
Published: February 2016

Aim

A discussion on how informatics knowledge and competencies can enable nursing to instantiate transition to integrated models of care.

Background

Costs of traditional models of care are no longer sustainable consequent to the spiralling incidence and costs of chronic illness. The international community looks towards technology‐enabled solutions to support a shift towards integrated patient‐centred models of care.

Design

Discussion paper.

Data sources

A search of the literature was performed dating from 2000–2015 and a purposeful data sample based on relevance to building the discussion was included.

Discussion

The holistic perspective of nursing knowledge can support and advance integrated healthcare models. Informatics skills are key for the profession to play a leadership role in design, implementation and operation of next generation health care. However, evidence suggests that nursing engagement with informatics strategic development for healthcare provision is currently variable.

Implications for nursing

A statistically significant need exists to progress health care towards integrated models of care. Strategic and tactical plans that are robustly pragmatic with nursing insights and expertise are an essential component to achieve effective healthcare provision. To avoid exclusion in the discourse dominated by management and technology experts, nursing leaders must develop and actively promote the advancement of nursing informatics skills. For knowledge in nursing practice to flourish in contemporary health care, nurse leaders will need to incorporate informatics for optimal translation and interpretation.

Conclusion

Defined nursing leadership roles informed by informatics are essential to generate concrete solutions sustaining nursing practice in integrated care models.
Personal Sovereignty and Our Moral Rights to Non‐Interference
Authors: Burri Susanne
Published: February 2016

In this article, I defend the inviolability approach to solving the paradox of deontology against a criticism raised by Michael Otsuka.

The paradox of deontology revolves around the question whether it should always be permissible to infringe someone's right to non‐interference when this would serve to minimize the overall number of comparable rights infringements that occur. According to the inviolability approach, rights to non‐interference protect and give expression to our personal sovereignty, which is not advanced through the minimization of rights infringements. This seems to dissolve the paradox. Otsuka, however, contends that the proposed solution relies on too narrow an understanding of personal sovereignty. He argues that there is an enforceability dimension to personal sovereignty that would seem to undermine the inviolability approach.

While I agree with Otsuka that enforceability is an important aspect of personal sovereignty, I argue that properly construed, the enforceability dimension of personal sovereignty does not undermine the inviolability approach.
Toxic Funding? Conflicts of Interest and their Epistemological Significance
Authors: Almassi Ben
Published: February 2016

Conflict of interest (COI) disclosure has become a routine requirement in communication of scientific information. Its advocates defend COI disclosure as a sensible middle path between the extremes of categorical prohibition on for‐profit research and anything‐goes acceptance of research regardless of origin. To the extent that COI information is meant to aid reviewer and reader evaluation of research, COIs must be epistemologically significant. While some commentators treat COIs as always relevant to research credibility, others liken the demand for disclosure to an ad hominem attack, impugning integrity when better evidence of research credibility is available. Kevin Elliott has argued for clearer justification of COI relevance to research credibility: some interests may be feared to corrupt research results, while others do not, and Elliott provides criteria to discern which financial COIs are actually relevant to research credibility. In this article, I seek to revise and extend Elliott's proposed criteria to COIs more widely. Specifically, I consider the relevance of financial interests as well as nonfinancial advocacy interests to the credibility of research into environmental equity as funded by industry and community groups, with particular attention to criticism and defence of the 1987 United Church of Christ study on the racial demographics of toxic waste facility siting in the United States.
The Choice of Debt Source by UK Firms
Authors: Marshall Andrew , Mccann Laura , Mccolgan Patrick
Published: February 2016

We examine the choice of borrowing source among public debt, syndicated bank loans, bilateral bank loans and non‐bank private debt. Using a sample of 400 non‐financial firms over the period 2000–2012, we find strong support for the reputational theory of borrowing source. Larger firms are more likely to borrow in public debt markets. Bank dependent firms are less likely to borrow in public debt markets and choose between bank and non‐bank private debt based on maturity, collateral available to lenders and other firm characteristics. These results are consistent with the role of borrower reputation being the primary determinant of borrowing source for UK listed firms.
Does the Riskiness of R&D Outweigh Its Benefits? The Perspective of US Private Lenders
Authors: Ciftci Mustafa , Darrough Masako
Published: February 2016

We investigate the relationship between R&D investments and loan spread. Prior research documents that R&D is associated with greater future benefits and risks, suggesting that the valuation of R&D depends on a tradeoff between the two. Some research finds that bondholders consider that the benefits of R&D outweigh its risks: R&D is negatively associated with bond yields. This is surprising given that debt holders are more concerned about downside risk due to asymmetric payoffs. Using data on private debt from the US, we find an overall positive association between loan spread and R&D intensity, suggesting that the riskiness of R&D appears to outweigh its benefits for private lenders. Furthermore, an asymmetric payoff structure implies that the risks of R&D for lenders increase with default risk. Consistent with this argument, we find a positive association between R&D and loan spread for firms that are smaller, with high default‐risk ratings, unrated (no public debt), or in industries with weaker legal protection. Unrated firms are in the most R&D‐intensive group and make up nearly 60% of the firms with private debt. Consequently, studies that exclude unrated firms are likely to present an incomplete picture of the perspective of debt holders on R&D.
Updating the Europe–Africa small mammal exchange during the late Messinian
Authors: García‐Alix Antonio , Minwer‐Barakat Raef , Martín Suárez Elvira , Freudenthal Matthijs , Aguirre Julio , Kaya Ferhat
Published: February 2016

Aim

The Messinian salinity crisis (MSC) was an extraordinary geological event that affected the whole Mediterranean region as well as the global marine circulation between 5.97 and c. 5.33 Ma. One of its most direct effects was the emersion of land masses and the subsequent establishment of land bridges that led to common terrestrial faunal exchanges. However, the details of the onset of these exchanges have been a matter of controversy. New findings from southern Iberia of small mammal remains with African similarities have enabled us to review the Messinian faunal exchanges in the Mediterranean region.

Location

Mediterranean region.

Methods

Small mammal remains with African similarities from two new southern Iberian sites were studied. The small mammal associations of eight Miocene–Pliocene North African sites were also reviewed.

Results

Two taxa with African similarities were identified at the Iberian study sites: Debruijnimys almenarensis and a Ruscinomys‐like form (cf. Ruscinomys) with a strong spur in the lingual lobe of the anterocone in the M1, a feature observed in North African Ruscinomys and eastern Mediterranean Byzantinia. The taxonomic status of some North African species and/or genera, such as Castillomys, Occitanomys and Prolagus, should be revised according to the new phylogenetic relationships established in European faunas.

Main conclusions

Two hypotheses can be proposed for the origin of the African Ruscinomys: (1) among the Iberian Ruscinomys or (2) from the eastern Mediterranean Byzantinia. Our data, currently from only a few, albeit significant, taxa, tend to support an Iberian origin. The discussion presented in this paper suggests an age near the closure of the last Betic Gateway (c. 6.18 Ma) for the first small mammal exchange between Africa and Europe, as well as a single migratory wave of small mammals, filtered by their ecological preferences from this point until the end of the MSC.
Nocturnal Hypertension and Subclinical Cardiac and Carotid Damage: An Updated Review and Meta‐Analysis of Echocardiographic Studies
Authors: Cuspidi Cesare , Sala Carla , Tadic Marijana , Gherbesi Elisa , Grassi Guido , Mancia Giuseppe
Published: February 2016

Evidence on the association of nocturnal hypertension (NH) with subclinical cardiac and vascular damage is scanty. The authors performed a meta‐analysis to provide comprehensive information on this clinically relevant issue. Full articles providing data on subclinical cardiac and carotid damage as assessed by ultrasonographic methods in patients with NH as compared with patients with nocturnal normotension (NN) were considered. A total of 3657 patients (NH=2083, NN=1574) of both sexes were included in seven studies. Left ventricular mass index was higher in individuals with NH than in those with NN (112±4.7 g/m2 vs 98±4.8 g/m2; standard mean difference [SMD], 0.54±0.16; confidence interval [CI], 0.23–0.85; P<.01). Similarly, common carotid intima‐media thickness was greater in patients with NH than in those with NN (751±34 μm vs 653±14 μm; SMD, 0.44±0.08; CI, 0.29–0.59; P<.01). The present meta‐analysis shows an association between NH pattern and increased likelihood of cardiac and carotid structural alterations.