bluuebunny/crossref_metadata_2025 huggingface dataset:
Local field potentials primarily reflect inhibitory neuron activity in human and monkey cortex
Authors: Teleńczuk Bartosz , Dehghani Nima , Le Van Quyen Michel , Cash Sydney S. , Halgren Eric , Hatsopoulos Nicholas G. , Destexhe Alain
Published: May 2016

The local field potential (LFP) is generated by large populations of neurons, but unitary contribution of spiking neurons to LFP is not well characterised. We investigated this contribution in multi-electrode array recordings from human and monkey neocortex by examining the spike-triggered LFP average (st-LFP). The resulting st-LFPs were dominated by broad spatio-temporal components due to ongoing activity, synaptic inputs and recurrent connectivity. To reduce the spatial reach of the st-LFP and observe the local field related to a single spike we applied a spatial filter, whose weights were adapted to the covariance of ongoing LFP. The filtered st-LFPs were limited to the perimeter of 800μm around the neuron, and propagated at axonal speed, which is consistent with their unitary nature. In addition, we discriminated between putative inhibitory and excitatory neurons and found that the inhibitory st-LFP peaked at shorter latencies, consistently with previous findings in hippocampal slices. Thus, in human and monkey neocortex, the LFP reflects primarily inhibitory neuron activity.
Reference-based phasing using the Haplotype Reference Consortium panel
Authors: Loh Po-Ru , Danecek Petr , Palamara Pier Francesco , Fuchsberger Christian , Reshef Yakir A , Finucane Hilary K , Schoenherr Sebastian , Forer Lukas , McCarthy Shane , Abecasis Goncalo R , Durbin Richard , Price Alkes L
Published: May 2016

Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing within a genotyped cohort, an approach that can attain high accuracy in very large cohorts but attains lower accuracy in smaller cohorts. Here, we instead explore the paradigm of reference-based phasing. We introduce a new phasing algorithm, Eagle2, that attains high accuracy across a broad range of cohort sizes by efficiently leveraging information from large external reference panels (such as the Haplotype Reference Consortium, HRC) using a new data structure based on the positional BurrowsWheeler transform. We demonstrate that Eagle2 attains a ≈20x speedup and ≈10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2x the accuracy of 1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC-based phasing via the Sanger Imputation Service and the Michigan Imputation Server.
Divergent Immune Priming Responses Across Flour Beetle Life Stages and Populations
Authors: Khan Imroze , Prakash Arun , Agashe Deepa
Published: May 2016

Growing evidence shows that low doses of pathogens may prime the immune response in many insects, conferring subsequent protection against infection in the same developmental stage (within life stage priming), across life stages (ontogenic priming), or to offspring (trans-generational priming). Recent work also suggests that immune priming is a costly response. Thus, depending on host and pathogen ecology and evolutionary history, tradeoffs with other fitness components may constrain the evolution of priming. However, the relative impacts of priming at different life stages and across natural populations remain unknown. We quantified immune priming responses of 10 natural populations of the red flour beetleTribolium castaneum, primed and infected with the natural insect pathogenBacillus thuringiensis. We found that priming responses were highly variable both across life stages and populations, ranging from no detectable response to a 13-fold survival benefit. Comparing across stages, we found that ontogenic immune priming at the larval stage conferred maximum protection against infection. Finally, we found that various forms of priming showed sex-specific associations that may represent tradeoffs or shared mechanisms. These results suggest that sex-, life stage-, and pathogen-specific selective pressures can cause substantial divergence in priming responses even within a species. Our work highlights the necessity of further work to understand the mechanistic basis of this variability.
A hot L1 retrotransposon evades somatic repression and initiates human colorectal cancer
Authors: Scott Emma C. , Gardner Eugene J. , Masood Ashiq , Chuang Nelson T. , Vertino Paula M. , Devine Scott E.
Published: May 2016

Although human LINE-1 (L1) elements are actively mobilized in many cancers, a role for somatic L1 retrotransposition in tumor initiation has not been conclusively demonstrated. Here, we identify a novel somatic L1 insertion in the APC tumor suppressor gene that provided us with a unique opportunity to determine whether such insertions can actually initiate colorectal cancer (CRC), and if so, how this might occur. Our data support a model whereby a hot L1 source element on Chromosome 17 of the patient's genome evaded somatic repression in normal colon tissues and thereby initiated CRC by mutating the APC gene. This insertion worked together with a point mutation in the second APC allele to initiate tumorigenesis through the classic two-hit CRC pathway. We also show that L1 source profiles vary considerably depending on the ancestry of an individual, and that population-specific hot L1 elements represent a novel form of cancer risk.
Neutron diffraction study of (KxNa1−x)NbO3-based ceramics from low to high temperatures
Authors: Mgbemere Henry , Schneider Gerold , Hoelzel Markus , Hinterstein Manuel
Published: May 2016

A neutron diffraction study of (KxNa1−x)NbO3-based ceramics has been carried out from 5 K to high temperatures well above the Curie temperature. The diffraction data were analysed using Rietveld refinement. For pure KNN samples, especially at the Na-rich side of the phase diagram, the low-temperature structure of simple rhombohedral symmetry changes to a highly complex monoclinic structure at a higher temperature. Chemical analysis on the samples showed good agreement of the expected and actual compositions. Trigonal, monoclinic, orthorhombic, tetragonal and cubic phase models as well as two-phase mixtures are observed depending on the temperature of measurement. Space groupsR3c,P1m1,P11m,Amm2,P4mm, Pm\overline 3m and their combinations are used to refine the trigonal, monoclinic, orthorhombic, tetragonal, cubic and mixed phases, respectively. For the (K0.48Na0.48Li0.04)(Nb0.86Ta0.1Sb0.04)O3sample at temperatures between 5 and 300 K, the monoclinicP11mspace group gives the best refinement fit. For the (K0.17Na0.83)NbO3sample, a two-phase refinement using the trigonalR3cand monoclinicPmspace groups gave the best fit at 300 K, while at 5–150 K the trigonalR3cspace group gives the best fit. The understanding of the structure of these lead-free ceramics will help in the optimization of their piezoelectric properties.
Retrieving the spatially resolved preferred orientation of embedded anisotropic particles by small-angle X-ray scattering tomography
Authors: Skjønsfjell Eirik Torbjørn , Kringeland Torbjørn , Granlund Håvard , Høydalsvik Kristin , Diaz Ana , Breiby Dag Werner
Published: May 2016

Experimental nondestructive methods for probing the spatially varying arrangement and orientation of ultrastructures in hierarchical materials are in high demand. While conventional computed tomography (CT) is the method of choice for nondestructively imaging the interior of objects in three dimensions, it retrieves only scalar density fields. In addition to the traditional absorption contrast, other contrast mechanisms for image formation based on scattering and refraction are increasingly used in combination with CT methods, improving both the spatial resolution and the ability to distinguish materials of similar density. Being able to obtain vectorial information, like local growth directions and crystallite orientations, in addition to scalar density fields, is a longstanding scientific desire. In this work, it is demonstrated that, under certain conditions, the spatially varying preferred orientation of anisotropic particles embedded in a homogeneous matrix can be retrieved using CT with small-angle X-ray scattering as the contrast mechanism. Specifically, orientation maps of filler talc particles in injection-moulded isotactic polypropylene are obtained nondestructively under the key assumptions that the preferred orientation varies slowly in space and that the orientation of the flake-shaped talc particles is confined to a plane. It is expected that the method will find application inin situstudies of the mechanical deformation of composites and other materials with hierarchical structures over a range of length scales.
IOTA: integration optimization, triage and analysis tool for the processing of XFEL diffraction images
Authors: Lyubimov Artem Y. , Uervirojnangkoorn Monarin , Zeldin Oliver B. , Brewster Aaron S. , Murray Thomas D. , Sauter Nicholas K. , Berger James M. , Weis William I. , Brunger Axel T.
Published: May 2016

Serial femtosecond crystallography (SFX) uses an X-ray free-electron laser to extract diffraction data from crystals not amenable to conventional X-ray light sources owing to their small size or radiation sensitivity. However, a limitation of SFX is the high variability of the diffraction images that are obtained. As a result, it is often difficult to determine optimal indexing and integration parameters for the individual diffraction images. Presented here is a software package, calledIOTA, which uses a grid-search technique to determine optimal spot-finding parameters that can in turn affect the success of indexing and the quality of integration on an image-by-image basis. Integration results can be filtered usinga prioriinformation about the Bravais lattice and unit-cell dimensions and analyzed for unit-cell isomorphism, facilitating an improvement in subsequent data-processing steps.
On the release ofcppxfelfor processing X-ray free-electron laser images
Authors: Ginn Helen Mary , Evans Gwyndaf , Sauter Nicholas K. , Stuart David Ian
Published: May 2016

As serial femtosecond crystallography expands towards a variety of delivery methods, including chip-based methods, and smaller collected data sets, the requirement to optimize the data analysis to produce maximum structure quality is becoming increasingly pressing. Herecppxfel, a software package primarily written in C++, which showcases several data analysis techniques, is released. This software package presently indexes images using DIALS (diffraction integration for advanced light sources) and performs an initial orientation matrix refinement, followed by post-refinement of individual images against a reference data set.Cppxfelis released with the hope that the unique and useful elements of this package can be repurposed for existing software packages. However, as released, it produces high-quality crystal structures and is therefore likely to be also useful to experienced users of X-ray free-electron laser (XFEL) software who wish to maximize the information extracted from a limited number of XFEL images.
Modeling truncated pixel values of faint reflections in MicroED images
Authors: Hattne Johan , Shi Dan , de la Cruz M. Jason , Reyes Francis E. , Gonen Tamir
Published: May 2016

The weak pixel counts surrounding the Bragg spots in a diffraction image are important for establishing a model of the background underneath the peak and estimating the reliability of the integrated intensities. Under certain circumstances, particularly with equipment not optimized for low-intensity measurements, these pixel values may be corrupted by corrections applied to the raw image. This can lead to truncation of low pixel counts, resulting in anomalies in the integrated Bragg intensities, such as systematically higher signal-to-noise ratios. A correction for this effect can be approximated by a three-parameter lognormal distribution fitted to the weakly positive-valued pixels at similar scattering angles. The procedure is validated by the improved refinement of an atomic model against structure factor amplitudes derived from corrected micro-electron diffraction (MicroED) images.
Deferoxamine alleviates liver fibrosis induced by CCl4 in rats
Authors: Mohammed Aya , Abd Al Haleem Ekram N , El‐Bakly Wesam M , El‐Demerdash Ebtehal
Published: May 2016

Several chronic liver diseases can lead to the occurrence of hepatic fibrosis through the accumulation of iron, which causes induction of oxidative stress and consequently activation of fibrogenesis. The present study was designed to investigate the potential antifibrotic and anti‐oxidant effects of deferoxamine (DFO), a well‐known iron chelator in an experimental rat model of liver injury using carbon tetrachloride (CCl4). First, the potential effective dose of DFO was screened against CCl4‐induced acute hepatotoxicity. Then, rats were co‐treated with DFO (300 mg/kg, i.p.) for 6 weeks starting from the third week of CCl4 induction of chronic hepatotoxicity. Liver function was assessed in addition to histopathological examination. Furthermore, oxidative stress and fibrosis markers were assessed. It was found that treatment of animals with DFO significantly counteracted the changes in liver function; histopathological lesions and hepatic iron deposition that were induced by CCl4. DFO also significantly counteracted the CCl4‐induced lipid peroxidation increase and reduction in antioxidant activities of superoxide dismutase and glutathione peroxidase enzymes. In addition, DFO ameliorated significantly liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cells (HSCs) activation marker; alpha smooth muscle actin and transforming growth factor‐beta (TGF‐β). Together, these findings indicate that DFO possesses a potent antifibrotic effect due to its antioxidant properties that counteracted oxidative stress and lipid peroxidation and restored antioxidant enzymes activities as well as reducing HSCs activation and fibrogenesis.
Genome‐wide association study reveals novel variants for growth and egg traits in Dongxiang blue‐shelled and White Leghorn chickens
Authors: Liao R. , Zhang X. , Chen Q. , Wang Z. , Wang Q. , Yang C. , Pan Y.
Published: May 2016

This study was designed to investigate the genetic basis of growth and egg traits in Dongxiang blue‐shelled chickens and White Leghorn chickens. In this study, we employed a reduced representation sequencing approach called genotyping by genome reducing and sequencing to detect genome‐wide SNPs in 252 Dongxiang blue‐shelled chickens and 252 White Leghorn chickens. The Dongxiang blue‐shelled chicken breed has many specific traits and is characterized by blue‐shelled eggs, black plumage, black skin, black bone and black organs. The White Leghorn chicken is an egg‐type breed with high productivity. As multibreed genome‐wide association studies (GWASs) can improve precision due to less linkage disequilibrium across breeds, a multibreed GWAS was performed with 156 575 SNPs to identify the associated variants underlying growth and egg traits within the two chicken breeds. The analysis revealed 32 SNPs exhibiting a significant genome‐wide association with growth and egg traits. Some of the significant SNPs are located in genes that are known to impact growth and egg traits, but nearly half of the significant SNPs are located in genes with unclear functions in chickens. To our knowledge, this is the first multibreed genome‐wide report for the genetics of growth and egg traits in the Dongxiang blue‐shelled and White Leghorn chickens.
The Production, Distribution and Consumption of Metals and Alloys at Great Zimbabwe
Authors: Bandama F. , Moffett A. J. , Thondhlana T. P. , Chirikure S.
Published: May 2016

The legacy of vandalism and almost a century of continuous focus on drystone wall masonry is that little is known about metal craft production and consumption activities at Great Zimbabwe. Within these limitations, this paper attempts to explore the metallurgy of Great Zimbabwe, guided by the framework of archival, chronological and fieldwork‐ and laboratory‐based studies. The paper contends that residents of various components of Great Zimbabwe worked and processed their own metal, pointing to homestead‐level production and consumption. Metal from local and regional sources sustained long‐distance trade with the Indian Ocean rim.
Rare complication after totally extraperitoneal endoscopic inguinal hernia repair: Small bowel perforation without peritoneal disruption
Authors: Kojima Shigehiro , Sakamoto Tsuguo , Honda Masayuki , Nishiguchi Ryohei , Ogawa Fumihiro
Published: May 2016

We report a rare case of visceral injury after totally extraperitoneal endoscopic inguinal hernia repair. A 48‐year‐old man underwent needlescopic totally extraperitoneal repair of a direct inguinal hernia. Bleeding from a branch of the inferior epigastric vessels occurred at the beginning of the extraperitoneal dissection with a monopolar electrosurgical device. Hemostasis was prolonged. However, herniorrhaphy and mesh repair were successfully performed, and no peritoneal disruption or pneumoperitoneum was visible. The patient was discharged home on the next day. However, 30 h after this operation, he underwent diagnostic and operative laparoscopy because of acute abdominal pain. Ileal perforation was found and repaired, and pathological examination indicated cautery artifact. Thus, thermal damage to the ileum during the initial operation may have caused the bowel perforation. To the best of our knowledge, no other cases of bowel perforation after totally extraperitoneal repair without peritoneal disruption have been reported.
Revisiting the validity of measures of social cognitive bias in schizophrenia: Additional results from the Social Cognition Psychometric Evaluation (SCOPE) study
Authors: Buck Benjamin E. , Pinkham Amy E. , Harvey Philip D. , Penn David L.
Published: May 2016

Objective

The ongoing Social Cognition Psychometric Evaluation (SCOPE) study is in the process of forming a gold‐standard battery of social cognition tests for use in clinical trials. Previous SCOPE phases have not acknowledged key differences between social cognition skills and biases, and psychometric validity analyses might provide important information if tailored to bias‐related outcomes. This study aims to validate these measures with such bias‐related outcomes.

Methods

Two measures of social cognitive bias – the Ambiguous Intention Hostility Questionnaire (AIHQ; hostile attribution bias) and Trustworthiness Task (distrust bias) – were reviewed according to their relationships to (1) current and prospective symptom levels, (2) questionnaires of trait paranoia and hostility and informant‐rated hostility, (3) interpersonal conflict, as well as (4) relationships to measures of trait paranoia, hostility, and interpersonal conflict above and beyond the influence of clinically rated symptoms.

Results

Results supported hypotheses that social cognitive bias provides information about cognition, symptoms, and functioning related to interpersonal conflict. Each bias demonstrated relationships to trait paranoia questionnaires, hostility, or interpersonal conflict outcomes, and these persisted above and beyond the influence of clinically rated symptoms. Hostile attribution bias also predicted change in symptom levels over a brief interval.

Conclusions

Overall, the current bias‐specific psychometric analysis provides support for continued study of social cognitive biases.

Practitioner points

Hostile attribution bias may play a role in important outcome variables given relationships to emotional discomfort and suspiciousness symptoms, trait paranoia and hostility, interpersonal conflict, as well as prospective hostility symptoms.

Distrust bias may also impact real‐world functioning, as it is related to hostility, suspiciousness, and positive symptoms, trait paranoia, and hostility.

Relationships of social cognitive biases to interpersonal conflict outcomes exist independently of interview‐rated symptoms and persist above and beyond the influence of social cognitive skills, which appear to demonstrate weaker relationships to these outcomes.

Understanding and assessing the individual's biases towards distrust or blame might help practioners predict interpersonal conflict and future increases in symptoms.
CAPITAL AND INEQUALITY
Authors: Mirrlees James A.
Published: May 2016

Wealth inequality comes about mainly as a result of lifetime accumulation of capital and risky investment. Evidence from the Forbes Rich Lists show that in recent years volatility of the wealth of the richest has been very great. Randomness of returns to capital can explain a substantial part of global wealth inequality. As a consequence, inequality can best be reduced by a tax on returns to capital in excess of a normal rate of return, in addition to tax on labor earnings. (JEL D31)
Auditory brainstem maturation in normal‐hearing infants born preterm: a meta‐analysis
Authors: Stipdonk Lottie W , Weisglas‐Kuperus Nynke , Franken Marie‐Christine JP , Nasserinejad Kazem , Dudink Jeroen , Goedegebure André
Published: May 2016

Aim

Children born preterm often have neurodevelopmental problems later in life. Abnormal maturation of the auditory brainstem in the presence of normal hearing might be a marker for these problems. We conducted a meta‐analysis of auditory brainstem response (ABR) latencies at term age to describe differences in auditory brainstem maturation between normal‐hearing preterm and term‐born infants.

Method

Computerized databases were searched for studies published between 1995 and 2014 that reported ABR measurements at term age in infants born preterm in a case–control design. Five peaks reflect the conduction of a neural signal along the brainstem auditory pathway. We collected I to V interpeak latency data, and III to V interpeak latency data, which refers to the more central part of the pathway.

Results

Preterm‐born infants’ III to V interval is significantly longer compared to infants born at term (0.081ms, effect‐size=0.974), which also reflects on the I to V interval. Moreover, significantly increased ABR interpeak latencies of infants born preterm are related to lower gestational age and the need for neonatal intensive care treatment.

Interpretation

The delayed conduction time towards and into the auditory brainstem at term age suggests atypical maturation of the brainstem in normal‐hearing infants born preterm. Both the duration of gestation and the consequences of the preterm birth (intensive care needed) negatively affect maturation of the auditory brainstem, which may influence later development.
A European multicentre survey of impulse control behaviours in Parkinson's disease patients treated with short‐ and long‐acting dopamine agonists
Authors: Rizos A. , Sauerbier A. , Antonini A. , Weintraub D. , Martinez‐Martin P. , Kessel B. , Henriksen T. , Falup‐Pecurariu C. , Silverdale M. , Durner G. , Røkenes Karlsen K. , Grilo M. , Odin P. , Chaudhuri K. Ray ,   EUROPAR and the IPMDS Non‐Motor‐PD‐Study Group
Published: May 2016

Background and purpose

Impulse control disorders (ICDs) in Parkinson's disease (PD) are associated primarily with dopamine agonist (DA) use. Comparative surveys of clinical occurrence of impulse control behaviours on longer acting/transdermal DA therapy across age ranges are lacking. The aim of this study was to assess the occurrence of ICDs in PD patients across several European centres treated with short‐ or long‐acting [ropinirole (ROP); pramipexole (PPX)] and transdermal [rotigotine skin patch (RTG)] DAs, based on clinical survey as part of routine clinical care.

Methods

A survey based on medical records and clinical interviews of patients initiating or initiated on DA treatment (both short‐ and long‐acting, and transdermal) across a broad range of disease stages and age groups was performed.

Results

Four hundred and twenty‐five cases were included [mean age 68.3 years (range 37–90), mean duration of disease 7.5 years (range 0–37)]. ICD frequencies (as assessed by clinical interview) were significantly lower with RTG (4.9%; P < 0.05) compared with any other assessed DAs except for prolonged release PPX (PPX‐PR). The rate of ICDs for PPX‐PR (6.6%) was significantly lower than for immediate release PPX (PPX‐IR) (19.0%; P < 0.05). Discontinuation rates of DA therapy due to ICDs were low.

Conclusion

Our data suggest a relatively low rate of ICDs with long‐acting or transdermal DAs, however these preliminary observational data need to be confirmed with prospective studies controlling for possible confounding factors.
An Experiment on Forward vs. Backward Induction: How Fairness and Level k Reasoning Matter
Authors: Balkenborg Dieter , Nagel Rosemarie
Published: May 2016

We report the experimental results on a game with an outside option where forward induction contradicts with backward induction based on a focal, risk dominant equilibrium. The latter procedure yields the equilibrium selected by Harsanyi and Selten’s (1988) theory, which is hence here in contradiction with strategic stability (Kohlberg and Mertens, 1986). We find the Harsanyi-Selten solution to be in much better agreement with our data. Since fairness and bounded rationality seem to matter we discuss whether recent behavioral theories, in particular fairness theories and learning, might explain our findings. The fairness theories by Bolton and Ockenfels (2000), Charness and Rabin (2002), or Fehr and Schmidt (1999), when calibrated using experimental data on dictator- and ultimatum games, indeed predict that forward induction should play no role for our experiment and that the outside option should be chosen by all sufficiently selfish players. However, there is a multiplicity of ‘fairness equilibria’, some of which seem to be rejected because they require too many levels of reasoning. We show that learning theories based on naive priors could alternatively explain our results, but not that of closely related experiments.
Inter‐rater reliability of h‐index scores calculated by Web of Science and Scopus for clinical epidemiology scientists
Authors: Walker Benjamin , Alavifard Sepand , Roberts Surain , Lanes Andrea , Ramsay Tim , Boet Sylvain
Published: May 2016

Objective

We investigated the inter‐rater reliability of Web of Science (WoS) and Scopus when calculating the h‐index of 25 senior scientists in the Clinical Epidemiology Program of the Ottawa Hospital Research Institute.

Materials and methods

Bibliometric information and the h‐indices for the subjects were computed by four raters using the automatic calculators in WoS and Scopus. Correlation and agreement between ratings was assessed using Spearman's correlation coefficient and a Bland–Altman plot, respectively.

Results

Data could not be gathered from Google Scholar due to feasibility constraints. The Spearman's rank correlation between the h‐index of scientists calculated with WoS was 0.81 (95% CI 0.72–0.92) and with Scopus was 0.95 (95% CI 0.92–0.99). The Bland–Altman plot showed no significant rater bias in WoS and Scopus; however, the agreement between ratings is higher in Scopus compared to WoS.

Conclusion

Our results showed a stronger relationship and increased agreement between raters when calculating the h‐index of a scientist using Scopus compared to WoS. The higher inter‐rater reliability and simple user interface used in Scopus may render it the more effective database when calculating the h‐index of senior scientists in epidemiology.
Insurance Crisis or Liability Crisis? Medical Malpractice Claiming in Illinois, 1980–2010
Authors: Rahmati Mohammad , Hyman David A. , Black Bernard , Silver Charles
Published: May 2016

Since 1980, Illinois has experienced three medical malpractice insurance crises—in the mid‐1980s, mid‐1990s, and early‐2000s. Each time, Illinois responded by enacting tort reform. Using a previously unavailable database of closed medical malpractice (med mal) claims, maintained by the Illinois Department of Insurance, we analyze statewide trends in med mal claiming from 1980–2010, covering all three crises. Paid claim rates rose sharply from 1980–1985, roughly leveled off from 1986–1993, and then began a sustained decline. By 2010, paid claims rates were 75 percent lower than in the peak year (1991). Payout per claim has steadily increased since 1980, but these increases can be entirely explained by the virtual disappearance of smaller paid claims and claims involving less severe injuries. The total direct cost of med mal litigation (payouts and defense costs) rose sharply from 1980–1992, with a jump in 1991, and then declined steadily, with a more modest jump during 2000–2002, which persisted through 2006. Thus, of the three Illinois insurance crises, only the first coincided in time with a major change in claiming. Rather than becoming more generous over time, the Illinois med mal system has squeezed out claimants with less severe injuries and smaller claims.
Mortality Risk of Antipsychotic Dose and Duration in Nursing Home Residents with Chronic or Acute Indications
Authors: Simoni‐Wastila Linda , Wei Yu‐Jung , Lucas Judith A. , Brandt Nicole , Moyo Patience , Huang Ting‐Ying J. , Franey Christine S. , Harris Ilene
Published: May 2016

Objectives

To examine disease‐specific associations between antipsychotic dose and duration and all‐cause mortality.

Design

Retrospective cohort study.

Setting

A 5% random sample of Medicare beneficiaries who had a Minimum Data Set 2.0 clinical assessment completed between 2007 and 2009.

Participants

Three mutually exclusive cohorts of new antipsychotic users with evidence of severe mental illness (SMI, n = 5,621); dementia with behavioral symptoms (dementia + behavior) without SMI (n = 1,090); or delirium only without SMI or dementia + behavior (n = 2,100) were identified.

Measurements

Dose and duration of therapy with antipsychotics were assessed monthly with a 6‐month look‐back. Dose was measured as modified standardized daily dose (mSDD), with a mSDD of 1 or less considered below or at recommended maximum geriatric dose. Duration was categorized as 30 or fewer, 31 to 60, 61 to 90, and 91 to 184 days for SMI and dementia + behavior and 7 or fewer, 8 to 30, 31 to 90, and 91 to 184 days for delirium. Complementary log‐log models with mSDD and duration as time‐dependent variables were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.

Results

In all three groups, new antipsychotic users with a mSDD of 1 or less had significantly lower mortality risk (HRSMI = 0.77, 95% CI = 0.67–0.88; HRdementia+behavior = 0.52, 95% CI = 0.36–0.76; HRdelirium = 0.61, 95% CI = 0.44–0.85) than peers with a mSDD greater than 1. Individuals with longer duration of antipsychotic use (91–184 days for SMI and delirium) had significantly lower mortality than those with a short duration of use (≤30 days for SMI; ≤7 days for delirium). The interaction between dose and duration was statistically significant in the SMI cohort (P < .001).

Conclusion

Lower mortality was observed with within‐recommended dose ranges for dementia + behavior, SMI, and delirium and with long duration of antipsychotic use for the latter two disease groups. Prescribers should monitor antipsychotic dosage throughout the course of antipsychotic treatment and customize dose and duration regimens to an individual's indications.
BDNF isoforms: a round trip ticket between neurogenesis and serotonin?
Authors: Foltran Rocío Beatriz , Diaz Silvina Laura
Published: May 2016

The brain‐derived neurotrophic factor, BDNF, was discovered more than 30 years ago and, like other members of the neurotrophin family, this neuropeptide is synthetized as a proneurotrophin, the pro‐BDNF, which is further cleaved to yield mature BDNF. The myriad of actions of these two BDNF isoforms in the central nervous system is constantly increasing and requires the development of sophisticated tools and animal models to refine our understanding. This review is focused on BDNF isoforms, their participation in the process of neurogenesis taking place in the hippocampus of adult mammals, and the modulation of their expression by serotonergic agents. Interestingly, around this triumvirate of BDNF, serotonin, and neurogenesis, a series of recent research has emerged with apparently counterintuitive results. This calls for an exhaustive analysis of the data published so far and encourages thorough work in the quest for new hypotheses in the field.

image

BDNF is synthetized as a pre‐proneurotrophin. After removal of the pre‐region, proBDNF can be cleaved by intracellular or extracellular proteases. Mature BDNF can bind TrkB receptors, promoting their homodimerization and intracellular phosphorylation. Phosphorylated‐TrkB can activate three different signaling pathways. Whereas G‐protein‐coupled receptors can transactivate TrkB receptors, truncated forms can inhibit mBDNF signaling. Pro‐BDNF binds p75NTR by its mature domain, whereas the pro‐region binds co‐receptors.
Argon mediates protection by interleukin‐8 suppression via a TLR2/TLR4/STAT3/NF‐κB pathway in a model of apoptosis in neuroblastoma cells in vitro and following ischemia‐reperfusion injury in rat retina in vivo
Authors: Ulbrich Felix , Lerach Teresa , Biermann Julia , Kaufmann Kai B. , Lagreze Wolf A. , Buerkle Hartmut , Loop Torsten , Goebel Ulrich
Published: May 2016

Argon has recently come into scientific focus as a neuroprotective agent. The underlying neuroprotective mechanism remains unknown although toll‐like receptors were recently suggested to play an important role. We hypothesized that TLR‐associated downstream transcription factors are responsible for argon's effects, leading to anti‐apoptotic and anti‐inflammatory properties. Apoptosis was induced in human neuroblastoma cells. Immediately afterwards, argon treatment (75 Vol% for 2 h) was initiated. Cells were analyzed, measuring mitochondrial membrane potential, reactive‐oxygen‐species, annexin‐V/propidium iodide staining, transcription factor phosphorylation and binding activity as well as protein and mRNA expression of interleukins. Argon's in vivo effects were analyzed by quantification of retinal ganglion cell density, mRNA expression, serum cytokine analysis and immunohistochemistry after retinal ischemia reperfusion injury (IRI) in rats. Argon diminished rotenone‐induced kappa‐light‐chain‐enhancer' of activated B‐cells (NF‐κB) and signal transducer and activator of transcription 3 (STAT3) but not STAT5 or cAMP‐response element‐binding protein (CREB) phosphorylation and DNA‐binding activity. Argon treatment attenuated apoptosis by preservation of mitochondrial membrane potential and decline in reactive oxygen species (ROS) generation. NF‐κB and STAT3 inhibition, as well as TLR2 and TLR4 inhibition reversed argon's effects on IL‐8 mRNA expression. Argon attenuated rotenone‐induced IL‐8 protein and mRNA expression in vitro. Inhibition of TLR2 and 4 attenuated argon's protective effect in vivo reducing IRI driven retinal IL‐8 expression. IL‐8 expression was found in the retina in co‐localization with Müller cells and retinal ganglion cells. Argon mediates its neuroprotective effects by TLR‐mediated regulation of transcription factors NF‐κB and STAT3, thus decreasing interleukin‐8 expression in vitro and in vivo. These findings may open up new opportunities to effectively treat cerebral ischemia and reperfusion injury through the inhalation of argon.

image

Argon exerts its protective effects in vitro and in vivo via toll‐like receptors TLR2 and TLR4 signaling, followed by alteration of downstream enzymes. In conclusion, argon mediates its beneficial effects by suppression of STAT3 and NF‐κB phosphorylation and subsequent suppression of interleukin IL‐8 protein expression. These novel findings may open up opportunities for argon as a therapeutic agent, particularly in the treatment of neuronal injury.

Cover image for this issue: doi: 10.1111/jnc.13334.
Being an informal caregiver for a relative with liver cirrhosis and overt hepatic encephalopathy: a phenomenological study
Authors: Künzler‐Heule Patrizia , Beckmann Sonja , Mahrer‐Imhof Romy , Semela David , Händler‐Schuster Daniela
Published: May 2016

Aims and objectives

To explore the experiences of being an informal caregiver for a relative with liver cirrhosis and overt hepatic encephalopathy.

Background

Overt hepatic encephalopathy is a common complication in patients with liver cirrhosis. It is associated with decreased quality of life for patients, and presents a major burden for caregivers. The involvement of informal caregivers in medical care is recommended, but it has not been clearly described. An understanding of the experience of caregivers is needed to improve the support provided to them by healthcare professionals.

Design

A qualitative, interpretative, phenomenological approach was used.

Methods

Twelve informal caregivers participated in qualitative interviews. The analysis followed the six steps of the interpretative phenomenological approach.

Results

Caregivers' experiences were described using five themes: (1) feeling overwhelmed by their loved one having unexplainable symptoms and behaviours; (2) learning that this and previous experiences were complications of liver disease; (3) becoming aware of the symptoms of hepatic encephalopathy; (4) having feelings of being tied down and (5) experiencing and overcoming obstacles in working with healthcare professionals.

Conclusions

This study provides insight into caregivers' experiences and the consequences for their lives. The first occurrence of symptoms was a shock, but receiving the diagnosis was seen as an important step in understanding and learning. Caregivers provide daily assessments of their relatives' conditions, and they feel responsible for medication management. Over time, the caregivers impressively showed how they were able to incorporate their personal experiences into caregiving and to accept more accountability in managing the disease.

Relevance to clinical practice

Nurses should acknowledge caregivers as experts in caring for their loved ones. Nurses can assist caregivers in managing an episode of hepatic encephalopathy and can provide individualised interventions to ease the future burden.
Prenatal assessment of pulmonary maturity on 3‐D ultrasound
Authors: Wang Sha‐Sha , Tian Xue‐Ye , Yan Hong‐Wei , Yuan Ting , Zheng Xiao‐Ye , Han Zhen
Published: May 2016

Aim

The aim of this study was to assess the feasibility and accuracy of 3‐D ultrasound indices to evaluate fetal lung maturity, and to establish a normal reference for fetal lung volume (FLV) and fetal lung‐to‐liver intensity ratio (FLLIR) in a Chinese population.

Methods

A total of 1022 pregnant women with singleton pregnancy were prospectively studied between June 2008 to June 2011. Ultrasound examination was performed. The breathing‐related nasal fluid flow (BRNFF) spectrum, FLV, pulmonary artery blood flow parameters, and echo intensity of the lung were calculated. Phosphoglycerides in the amniotic fluid were measured on thin layer chromatography.

Results

FLLIR and FLV were positively and linearly correlated with gestational age (F = 0.915, 0.846). Indicators of fetal lung maturity included FLLIR >1.1, FLV >50 mL, and regular BRNFF spectrum, with positive likelihood ratios of 12.28, 11.78, and 11.63, independently.

Conclusion

Ultrasound indices, including FLLIR, FLV and BRNFF may serve as useful alternatives to amniotic fluid phospholipids in analyzing fetal lung maturity in Chinese patients.
A survey of Polytomella (Chlorophyceae, Chlorophyta) strains in public culture collections
Authors: MacDonald Shelley M. , Lee Robert W.
Published: May 2016

Polytomella is a genus of colorless green algae in the Reinhardtinia clade of the Chlamydomonadales, which has proven useful for a broad range of studies particularly those exploring the evolutionary loss of photosynthesis and mitochondrial genomics/biochemistry. Although 13 Polytomella strain accessions are currently available from public culture collections, the taxonomic status and redundancy of many of these strains is not clear because of possible mix‐ups, deficient historical records, and incomplete molecular data. This study therefore considers previously available and/or new cox1 and mitochondrial DNA telomere sequences from all 13 Polytomella strain accessions. Among four of these, namely P. parva SAG 63‐3, P. piriformis SAG 63‐10, P. capuana SAG 63‐5, and P. magna SAG 63‐9, cox1 and mitochondrial telomere regions are both highly divergent between strains. All of the remaining nine Polytomella strain accessions have cox1 sequences that are identical to that of P. parva SAG 63‐3 and although five of these have a mitochondrial telomere haplotype that is identical to that of P. parva SAG 63‐3, the remaining four have one of three different haplotypes. Among the 10 strains with identical cox1 sequences, we suggest that three of the telomere haplotypes are associated with distinct geographical isolates of Polytomella and the fourth evolved from one of these isolates during 50 years of active culture.
Understanding the coexistence of competing raptors by Markov chain analysis enhances conservation of vulnerable species
Authors: Sarà M. , Mascara R. , López‐López P.
Published: May 2016

Understanding ecological interactions among protected species is crucial for correct management to avoid conflicting outcomes of conservation planning. The occurrence of a superior competitor may drive the exclusion of a subordinate contestant, as in Sicily where the largest European population of the lanner falcon is declining because of potentially competing with the peregrine falcon. We measured the coexistence of these two ecologically equivalent species through null models and randomization algorithms on body sizes and ecological niche traits. Lanners and peregrines are morphologically very similar (Hutchinson ratios <1.3) and show 99% diet overlap, and both of these results predict competitive exclusion. In contrast, their use of diverse cliff substrates for breeding in different times of the season would predict coexistence. To compare these two mutually excluding hypotheses, we examined the pattern of inter‐specific transitions in 88 sites that were studied for 14 years (2000–2013) using a Markov chain (MC) occupancy state model, and checked the sensitivity and elasticity of the community structure to changes in transition probabilities. During the study period, 1144 territorial transitions occurred in peregrine and lanner territories, and the MCs were predicted to converge to a stable equilibrium in 2065. Markovian analysis suggested that temporal and spatial segregation of habitat during reproduction might prevail over anatomical specialization for hunting and diet, allowing species coexistence, despite the prediction that peregrines will outnumber the lanners in future projections. Our approach combining niche‐overlap analysis and species occupancy modelling led to practical information about conservation options available for the threatened lanner. Lanners are very sensitive to site abandonment, and measures increasing adult persistence in occupied territories could be more rewarding than those encouraging juvenile dispersal and colonization of new sites.
Population recovery highlights spatial organization dynamics in adult leopards
Authors: Fattebert J. , Balme G. A. , Robinson H. S. , Dickerson T. , Slotow R. , Hunter L. T. B.
Published: May 2016

Polygynous species follow sex‐specific spacing patterns to maximize reproductive success, and changes in population density under otherwise stable environmental conditions likely provoke sex‐specific responses in spacing patterns. A classical dual reproductive strategy hypothesis posits that female home range size and overlap are set by habitat productivity and remain stable under increasing population density, whereas male home range size and overlap decrease with increased mate competition. An alternative dispersal‐regulated strategy predicts that females relinquish part of their home range to philopatric daughters and form matrilineal clusters, while adult male spacing is stable with density‐dependent subadult male emigration rates. We used 11 years of telemetry data to assess the response of adult leopardPanthera pardusspacing following the release of harvest pressure. Female annual home ranges and core areas were smaller than in males. Intersexual overlap was larger than intra‐sexual overlap in males or in females. As leopard density increased, female home range size and inter‐annual fidelity in home range use decreased, and females formed matrilineal kin clusters. In contrast, male leopards maintained large home ranges, and did not track female home range contraction. Spacing dynamics in adult leopards was consistent with dispersal‐regulated strategies, and did not support a classical dual reproductive strategy. Our study suggests possible hidden lag effects of harvest disturbance on spacing dynamics that are not necessarily apparent when only assessing demographic recovery of harvested populations.
Physiological Roles of Bradykinin and Involvement of Bradykinin B2 Receptor in Urethral Function in Humans and Animals
Authors: FUJIMOTO Kenichiro , YOSHINO Taiji , NAKAJIMA Satoko , YUYAMA Hironori , MASUDA Noriyuki , TAKEDA Masahiro
Published: May 2016

Objective

We investigated the role of bradykinin in urethral function by examining contractile responses in urethral smooth muscle strips isolated from humans and the intraurethral pressure in rats and dogs.

Methods

The contractile responses of human urethral tissue for bradykinin (0.01–10 µmol/L) were examined, and changes in intraurethral pressure induced by bradykinin (0.003–10 µg/kg) in anesthetized rats or dogs were measured. In addition, the effects of pretreatment with the bradykinin B2 receptor antagonist FK3657 were also examined.

Results

In smooth muscle strips obtained from human urethra, bradykinin induced contraction, which was inhibited by FK3657 in a concentration‐dependent manner. In anesthetized rats and dogs, intravenously administered bradykinin dose‐dependently increased intraurethral pressure. FK3657 shifted the intraurethral pressure dose‐response curve for bradykinin to the right in rats. The bradykinin‐induced elevation of intraurethral pressure was also dose‐dependently inhibited by FK3657 in dogs.

Conclusions

The present study provides evidence that bradykinin elicits urethral smooth muscle contraction via the bradykinin B2 receptor, suggesting the potential utility of this receptor as a novel target for the treatment of voiding dysfunction.