bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal and daily climate variation have opposite effects on species elevational range size
Authors: Chan Wei-Ping , Chen I-Ching , Colwell Robert K. , Liu Wei-Chung , Huang Cho-ying , Shen Sheng-Feng
Published: March 2016

Variability for a day or a season

Species that experience larger seasonal climatic fluctuations are likely to be more physiologically flexible and thus likely to occur across a wider elevational range. Daily changes in temperature are also common but have rarely been considered. Chan
et al.
used a global data set of vertebrates to look at how these two different sets of variation affect a species' elevational distribution (see the Perspective by Perez
et al.
). Unexpectedly, larger daily fluctuations were associated with smaller elevational distributions. Thus, specialists are favored where daily fluctuations are dominant, whereas generalists are favored where seasonal fluctuations are the main climate influence.

Science
, this issue p.
1437
; see also p.
1392
Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury
Authors: Alidori Simone , Akhavein Nima , Thorek Daniel L. J. , Behling Katja , Romin Yevgeniy , Queen Dawn , Beattie Bradley J. , Manova-Todorova Katia , Bergkvist Magnus , Scheinberg David A. , McDevitt Michael R.
Published: March 2016

Fibrillar carbon nanotubes simultaneously deliver two small interfering RNAs, which safely prevent acute kidney injury and prolong survival in mice.
Targeting protein homeostasis in sporadic inclusion body myositis
Authors: Ahmed Mhoriam , Machado Pedro M. , Miller Adrian , Spicer Charlotte , Herbelin Laura , He Jianghua , Noel Janelle , Wang Yunxia , McVey April L. , Pasnoor Mamatha , Gallagher Philip , Statland Jeffrey , Lu Ching-Hua , Kalmar Bernadett , Brady Stefen , Sethi Huma , Samandouras George , Parton Matt , Holton Janice L. , Weston Anne , Collinson Lucy , Taylor J. Paul , Schiavo Giampietro , Hanna Michael G. , Barohn Richard J. , Dimachkie Mazen M. , Greensmith Linda
Published: March 2016

Augmenting the heat shock response with arimoclomol ameliorates pathology in cellular and animal models of inclusion body myositis.
Arginase-1–dependent promotion of T
H
17 differentiation and disease progression by MDSCs in systemic lupus erythematosus
Authors: Wu Hao , Zhen Yu , Ma Zhanchuan , Li Huimin , Yu Jinyu , Xu Zhong-Gao , Wang Xiang-Yang , Yi Huanfa , Yang Yong-Guang
Published: March 2016

MDSCs promote T
H
17 differentiation and systemic lupus erythematosus via arginase-1 production in patients and humanized mice.
Repurposing exosomes: The (magnetic) force awakens
Authors: Castro Cesar M.
Published: March 2016

Exosomes can be equipped with magnetism and drugs as anticancer strategies.
Commentary: One Small Step for the Gram Stain, One Giant Leap for Clinical Microbiology
Authors: Thomson Richard B.
Published: March 2016

The Gram stain is one of the most commonly performed tests in the clinical microbiology laboratory, yet it is poorly controlled and lacks standardization. It was once the best rapid test in microbiology, but it is no longer trusted by many clinicians. The publication by Samuel et al. (J. Clin. Microbiol. 54:1442–1447, 2016,
http://dx.doi.org/10.1128/JCM.03066-15
) is a start for those who want to evaluate and improve Gram stain performance. In an age of emerging rapid molecular results, is the Gram stain still relevant? How should clinical microbiologists respond to the call to reduce Gram stain error rates?
Multiplexed Anti-Toxoplasma IgG, IgM, and IgA Assay on Plasmonic Gold Chips: towards Making Mass Screening Possible with Dye Test Precision
Authors: Li Xiaoyang , Pomares Christelle , Gonfrier Géraldine , Koh Byumseok , Zhu Shoujun , Gong Ming , Montoya Jose G. , Dai Hongjie
Published: March 2016

Toxoplasmosis is an infection caused by the protozoan parasite
Toxoplasma gondii
that can lead to severe sequelae in the fetus during pregnancy. Definitive serologic diagnosis of the infection during gestation is made mostly by detecting
T. gondii
-specific antibodies, including IgG and IgM, individually in a single serum sample by using commercially available kits. The IgA test is used by some laboratories as an additional marker of acute infection. Most of the commercial tests have failed to reach 100% correlation with the reference method, the Sabin-Feldman dye test for the detection of
Toxoplasma
IgG antibodies. For
Toxoplasma
IgM and IgA antibodies, there is no reference method and their evaluation is done by comparing the results of one assay to those of another. There is a need for multiplexed assay platforms, as the serological diagnosis of
T. gondii
infection does not rely on the detection of a single Ig subtype. Here we describe the development of a plasmonic gold chip with vast fluorescence enhancement in the near-infrared region for simultaneous detection of IgG, IgM, and IgA antibodies against
T. gondii
in an ∼1-μl serum or whole-blood sample. When 168 samples were tested on this platform, IgG antibody detection sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. IgM antibody detection achieved 97.6% sensitivity and 96.9% specificity with a 90.9% PPV and a 99.2% NPV. Thus, the nanoscience-based plasmonic gold platform enables a high-performance, low-cost, multiplexed assay requiring ultrasmall blood volumes, paving the way for the implementation of universal screening for toxoplasmosis infection during gestation.
Late Maturation Steps Preceding Selective Nuclear Export and Egress of Progeny Parvovirus
Authors: Wolfisberg Raphael , Kempf Christoph , Ros Carlos
Published: March 2016

Although the mechanism is not well understood, growing evidence indicates that the nonenveloped parvovirus minute virus of mice (MVM) may actively egress before passive release through cell lysis. We have dissected the late maturation steps of the intranuclear progeny with the aims of confirming the existence of active prelytic egress and identifying critical capsid rearrangements required to initiate the process. By performing anion-exchange chromatography (AEX), we separated intranuclear progeny particles by their net surface charges. Apart from empty capsids (EC), two distinct populations of full capsids (FC) arose in the nuclei of infected cells. The earliest population of FC to appear was infectious but, like EC, could not be actively exported from the nucleus. Further maturation of this early population, involving the phosphorylation of surface residues, gave rise to a second, late population with nuclear export potential. While capsid surface phosphorylation was strictly associated with nuclear export capacity, mutational analysis revealed that the phosphoserine-rich N terminus of VP2 (N-VP2) was dispensable, although it contributed to passive release. The reverse situation was observed for the incoming particles, which were dephosphorylated in the endosomes. Our results confirm the existence of active prelytic egress and reveal a late phosphorylation event occurring in the nucleus as a selective factor for initiating the process.

IMPORTANCE
In general, the process of egress of enveloped viruses is active and involves host cell membranes. However, the release of nonenveloped viruses seems to rely more on cell lysis. At least for some nonenveloped viruses, an active process before passive release by cell lysis has been reported, although the underlying mechanism remains poorly understood. By using the nonenveloped model parvovirus minute virus of mice, we could confirm the existence of an active process of nuclear export and further characterize the associated capsid maturation steps. Following DNA packaging in the nucleus, capsids required further modifications, involving the phosphorylation of surface residues, to acquire nuclear export potential. Inversely, those surface residues were dephosphorylated on entering capsids. These spatially controlled phosphorylation-dephosphorylation events concurred with the nuclear export-import potential required to complete the infectious cycle.
The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues
Authors: Singh Birendra , Alvarado-Kristensson Maria , Johansson Martin , Hallgren Oskar , Westergren-Thorsson Gunilla , Mörgelin Matthias , Riesbeck Kristian
Published: March 2016

Moraxella catarrhalis
is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step in
M. catarrhalis
colonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role of
M. catarrhalis
interactions with collagens from various angles. Clinical isolates (
n
= 43) were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins.
M. catarrhalis
-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD) model was used to estimate the adherence of
M. catarrhalis
in vivo. We found that all
M. catarrhalis
clinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesins
u
biquitous
s
urface
p
rotein
A2
(UspA2) and UspA2H were identified as major collagen-binding receptors.
M. catarrhalis
wild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that the
M. catarrhalis
UspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease.

IMPORTANCE
The respiratory tract pathogen
Moraxella catarrhalis
adheres to the host by interacting with several components, including the ECM. Collagen accounts for 30% of total body proteins, and therefore, bacterial adherence to abundant host collagens mediates bacterial persistence and colonization. In this study, we characterized previously unknown
M. catarrhalis
-dependent interactions with host collagens and found that the trimeric autotransporter adhesins
u
biquitous
s
urface
p
rotein
A2
(UspA2) and UspA2H are highly important. Our observations also suggested that collagen-mediated adherence of
M. catarrhalis
is indispensable for bacterial survival in the host, as exemplified by a mouse COPD model.
Interaction between Simian Virus 40 Major Capsid Protein VP1 and Cell Surface Ganglioside GM1 Triggers Vacuole Formation
Authors: Luo Yong , Motamedi Nasim , Magaldi Thomas G. , Gee Gretchen V. , Atwood Walter J. , DiMaio Daniel
Published: March 2016

Simian virus 40 (SV40), a polyomavirus that has served as an important model to understand many aspects of biology, induces dramatic cytoplasmic vacuolization late during productive infection of monkey host cells. Although this activity led to the discovery of the virus in 1960, the mechanism of vacuolization is still not known. Pentamers of the major SV40 capsid protein VP1 bind to the ganglioside GM1, which serves as the cellular receptor for the virus. In this report, we show that binding of VP1 to cell surface GM1 plays a key role in SV40 infection-induced vacuolization. We previously showed that SV40 VP1 mutants defective for GM1 binding fail to induce vacuolization, even though they replicate efficiently. Here, we show that interfering with GM1-VP1 binding by knockdown of GM1 after infection is established abrogates vacuolization by wild-type SV40. Vacuole formation during permissive infection requires efficient virus release, and conditioned medium harvested late during SV40 infection rapidly induces vacuoles in a VP1- and GM1-dependent fashion. Furthermore, vacuolization can also be induced by a nonreplicating SV40 pseudovirus in a GM1-dependent manner, and a mutation in BK pseudovirus VP1 that generates GM1 binding confers vacuole-inducing activity. Vacuolization can also be triggered by purified pentamers of wild-type SV40 VP1, but not by GM1 binding-defective pentamers or by intracellular expression of VP1. These results demonstrate that SV40 infection-induced vacuolization is caused by the binding of released progeny viruses to GM1, thereby identifying the molecular trigger for the activity that led to the discovery of SV40.

IMPORTANCE
The DNA tumor virus SV40 was discovered more than a half century ago as a contaminant of poliovirus vaccine stocks, because it caused dramatic cytoplasmic vacuolization of permissive host cells. Although SV40 played a historically important role in the development of molecular and cellular biology, restriction mapping, molecular cloning, and whole-genome sequencing, the basis of this vacuolization phenotype was unknown. Here, we show that SV40-induced vacuolization is triggered by the binding of the major viral capsid protein, VP1, to a cell surface ganglioside receptor, GM1. No other viral proteins or virus replication is required for vacuole formation. Other polyomaviruses utilize different ganglioside receptors, but they do not induce vacuolization. This work identifies the molecular trigger for the phenotype that led to the discovery of this important virus and provides the first molecular insight into an unusual and enigmatic cytopathic effect due to virus infection.
Nonencapsulated Streptococcus pneumoniae: Emergence and Pathogenesis
Authors: Keller Lance E. , Robinson D. Ashley , McDaniel Larry S.
Published: March 2016

While significant protection from pneumococcal disease has been achieved by the use of polysaccharide and polysaccharide-protein conjugate vaccines, capsule-independent protection has been limited by serotype replacement along with disease caused by nonencapsulated
Streptococcus pneumoniae
(NESp). NESp strains compose approximately 3% to 19% of asymptomatic carriage isolates and harbor multiple antibiotic resistance genes. Surface proteins unique to NESp enhance colonization and virulence despite the lack of a capsule even though the capsule has been thought to be required for pneumococcal pathogenesis. Genes for pneumococcal surface proteins replace the capsular polysaccharide (cps) locus in some NESp isolates, and these proteins aid in pneumococcal colonization and otitis media (OM). NESp strains have been isolated from patients with invasive and noninvasive pneumococcal disease, but noninvasive diseases, specifically, conjunctivitis (85%) and OM (8%), are of higher prevalence. Conjunctival strains are commonly of the so-called classical NESp lineages defined by multilocus sequence types (STs) ST344 and ST448, while sporadic NESp lineages such as ST1106 are more commonly isolated from patients with other diseases. Interestingly, sporadic lineages have significantly higher rates of recombination than classical lineages. Higher rates of recombination can lead to increased acquisition of antibiotic resistance and virulence factors, increasing the risk of disease and hindering treatment. NESp strains are a significant proportion of the pneumococcal population, can cause disease, and may be increasing in prevalence in the population due to effects on the pneumococcal niche caused by pneumococcal vaccines. Current vaccines are ineffective against NESp, and further research is necessary to develop vaccines effective against both encapsulated and nonencapsulated pneumococci.
The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species
Authors: Schmoll Monika , Dattenböck Christoph , Carreras-Villaseñor Nohemí , Mendoza-Mendoza Artemio , Tisch Doris , Alemán Mario Ivan , Baker Scott E. , Brown Christopher , Cervantes-Badillo Mayte Guadalupe , Cetz-Chel José , Cristobal-Mondragon Gema Rosa , Delaye Luis , Esquivel-Naranjo Edgardo Ulises , Frischmann Alexa , Gallardo-Negrete Jose de Jesus , García-Esquivel Monica , Gomez-Rodriguez Elida Yazmin , Greenwood David R. , Hernández-Oñate Miguel , Kruszewska Joanna S. , Lawry Robert , Mora-Montes Hector M. , Muñoz-Centeno Tania , Nieto-Jacobo Maria Fernanda , Nogueira Lopez Guillermo , Olmedo-Monfil Vianey , Osorio-Concepcion Macario , Piłsyk Sebastian , Pomraning Kyle R. , Rodriguez-Iglesias Aroa , Rosales-Saavedra Maria Teresa , Sánchez-Arreguín J. Alejandro , Seidl-Seiboth Verena , Stewart Alison , Uresti-Rivera Edith Elena , Wang Chih-Li , Wang Ting-Fang , Zeilinger Susanne , Casas-Flores Sergio , Herrera-Estrella Alfredo
Published: March 2016

The genusTrichodermacontains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, comprehensive overview of the genomic content of these species for “hot topic” research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism inT. reesei,T. atroviride, andT. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of eachTrichodermaspecies discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved inN-linked glycosylation was detected, as were indications for the ability ofTrichodermaspp. to generate hybrid galactose-containingN-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique toTrichoderma, and these warrant further investigation. We found interesting expansions in theTrichodermagenus in several signaling pathways, such as G-protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique toT. atrovirideis the duplication of the alternative sulfur amino acid synthesis pathway.
Giant cell myocarditis: a life-threatening disorder heralded by orbital myositis
Authors: Ali Muhammad Sajawal , Mba Benjamin I , Husain Aliya Noor , Ciftci Farah Diba
Published: March 2016

A 40-year-old man with a history of orbital myositis (OM) presented to the emergency department with ventricular tachycardia requiring electrical cardioversion. Postcardioversion ECG showed right bundle branch block, while an echocardiogram revealed an ejection fraction of 20% and a dilated right ventricle. Cardiac MRI produced suboptimal images because the patient was having frequent arrhythmias. The rest of the work up, including coronary angiography, was unremarkable. Given the dilated right ventricle, we suspected arrhythmogenic right ventricular cardiomyopathy and discharged the patient with an implantable cardioverter-defibrillator. 1 week later, he was readmitted with cardiogenic shock; endomyocardial biopsy revealed giant cell myocarditis (GCM). To the best of our knowledge, this is the seventh case report of GCM described in a patient with OM. We recommend that clinicians maintain a high degree of suspicion for GCM in patients with OM presenting with cardiac problems.
Limbic encephalitis following immunotherapy against metastatic malignant melanoma
Authors: Salam Sharfaraz , Lavin Timothy , Turan Ayse
Published: March 2016

Novel immunotherapies are increasingly being used to treat malignant melanoma. The use of such agents has been associated with triggering autoimmunity. However, there has been a paucity in reports of limbic encephalitis associated with these immunotherapies. Pembrolizumab, a monoclonal antibody against programmed cell death antigen (PD-1), is currently being trialled in the UK to treat malignant melanoma. We report a unique case of antibody-negative limbic encephalitis presenting 1 year after starting pembrolizumab, in the context of malignant melanoma. The patient presented with progressive cognitive decline. MRI of the brain revealed signal change within the limbic structures. Cerebrospinal fluid studies confirmed evidence of inflammation with raised white cell count and protein. We were able to prevent further progression of symptoms by stopping pembrolizumab and treating the patient instead with steroids. We advocate considering autoimmune neuroinflammation as a differential for neurological disorders presenting in patients receiving PD-1 antagonist treatment and immunotherapy in general.
Protocol for the development and validation of a questionnaire to assess concerning behaviours and mental health in individuals with autism spectrum disorders: the Assessment of Concerning Behaviour (ACB) scale
Authors: Santosh Paramala , Tarver Joanne , Gibbons Felicity , Vitoratou Silia , Simonoff Emily
Published: March 2016

Introduction

Co-occurring psychiatric conditions and concerning behaviours are prevalent in individuals with autism spectrum disorders (ASD), and are likely to be detrimental to functioning and long-term outcomes. The cognitive rigidity and deficits in emotional literacy and verbal behaviour that commonly occur in ASD can adversely affect clinicians’ confidence to identify concerning behaviours and mental health problems. There is a need to develop a measure that is tailored towards individuals with ASD, and differentiates between symptoms of psychopathology and core ASD symptoms. Furthermore, it should be modified to capture internalising symptoms that individuals with ASD may find difficult or be unable to verbalise. This protocol describes the intended development and validation of the Assessment of Concerning Behaviour (ACB) scale. The ACB will aim to be a multidimensional measure of concerning behaviours in ASD incorporating self-report, parent/carer, teacher/employer and clinician report versions that can be used across the lifespan and spectrum of intellectual ability.

Methods and analysis

This study will be guided by the methods described in the US Food and Drug Administration Guidance for Industry Patient-reported Outcome Measures. A literature review, cognitive interviews and focus groups with individuals who have experience of working or living with ASDs will be used for item generation. A sample of children and adults with ASD will complete the ACB, in addition to other gold standard measures of concerning behaviour in order to establish the initial psychometric properties of the scale.

Ethics and dissemination

This study has received ethical approval from the NHS Research Ethics Committee: London-Camden and King's Cross (ref: 15/LO/0085). Study findings will be disseminated to healthcare professionals and scientists in the field through publication in peer-reviewed journals and conference presentations.
Value of systematic detection of physical child abuse at emergency rooms: a cross-sectional diagnostic accuracy study
Authors: Sittig Judith S , Uiterwaal Cuno S P M , Moons Karel G M , Russel Ingrid M B , Nievelstein Rutger A J , Nieuwenhuis Edward E S , van de Putte Elise M
Published: March 2016

Objectives

The aim of our diagnostic accuracy study Child Abuse Inventory at Emergency Rooms (CHAIN-ER) was to establish whether a widely used checklist accurately detects or excludes physical abuse among children presenting to ERs with physical injury.

Design

A large multicentre study with a 6-month follow-up.

Setting

4 ERs in The Netherlands.

Participants

4290 children aged 0–7 years attending the ER because of physical injury. All children were systematically tested with an easy-to-use child abuse checklist (index test). A national expert panel (reference standard) retrospectively assessed all children with positive screens and a 15% random sample of the children with negative screens for physical abuse, using additional information, namely, an injury history taken by a paediatrician, information provided by the general practitioner, youth doctor and social services by structured questionnaires, and 6-month follow-up information.

Main outcome measure

Physical child abuse.

Secondary outcome measure

Injury due to neglect and need for help.

Results

4253/4290 (99%) parents agreed to follow-up. At a prevalence of 0.07% (3/4253) for inflicted injury by expert panel decision, the positive predictive value of the checklist was 0.03 (95% CI 0.006 to 0.085), and the negative predictive value 1.0 (0.994 to 1.0). There was 100% (93 to 100) agreement about inflicted injury in children, with positive screens between the expert panel and child abuse experts.

Conclusions

Rare cases of inflicted injury among preschool children presenting at ERs for injury are very likely captured by easy-to-use checklists, but at very high false-positive rates. Subsequent assessment by child abuse experts can be safely restricted to children with positive screens at very low risk of missing cases of inflicted injury. Because of the high false positive rate, we do advise careful prior consideration of cost-effectiveness and clinical and societal implications before de novo implementation.
Validation of a metered dose inhaler electronic monitoring device: implications for asthma clinical trial use
Authors: Pilcher Janine , Holliday Mark , Ebmeier Stefan , McKinstry Steve , Messaoudi Fatiha , Weatherall Mark , Beasley Richard
Published: March 2016

Background

The SmartTouch Ventolin monitor (Adherium, Auckland, New Zealand) is an electronic monitor for use with a Ventolin metered dose inhaler, which records the date and time of inhaler actuations. This technology has the potential to allow in-depth analysis of patterns of inhaler use in clinical trial settings. The aim of this study was to determine the accuracy of the SmartTouch Ventolin monitor in recording Ventolin actuations.

Methods

20 SmartTouch Ventolin monitors were attached to Ventolin metered dose inhalers. Bench testing was performed over a 10-week period, to reflect the potential time frame between visits in a clinical trial. Inhaler actuations were recorded in a paper diary, which was compared with data uploaded from the monitors.

Results

2560 actuations were performed during the 10-week study period. Monitor sensitivity for diary-recorded actuations was 99.9% with a lower 97.5% confidence bound of 99.7%. The positive predictive value for diary-recorded actuations was 100% with a 97.5% lower confidence bound of 99.9%.

Conclusions

The SmartTouch Ventolin monitor is highly accurate in recording and retaining electronic data. It can be recommended for use in clinical trial settings in which training and quality control systems are incorporated into study protocols to ensure accurate data acquisition.
Immunochemical faecal occult blood testing to screen for colorectal cancer: can the screening interval be extended?
Authors: Haug Ulrike , Grobbee Esmée J , Lansdorp-Vogelaar Iris , Spaander Manon C W , Kuipers Ernst J
Published: March 2016

Objective

Colorectal cancer (CRC) screening programmes based on faecal immunochemical testing for haemoglobin (FIT) typically use a screening interval of 2 years. We aimed to estimate how alternative FIT strategies that use a lower than usual positivity threshold followed by a longer screening interval compare with conventional strategies.

Methods

We analysed longitudinal data of 4523 Dutch individuals (50–74 years at baseline) participating in round I of a one-sample FIT screening programme, of which 3427 individuals also participated in round II after 1–3 years. The cohort was followed until 2 years after round II. In both rounds, a cut-off level of ≥50 ng haemoglobin (Hb)/mL buffer (corresponding to 10 µg Hb/g faeces) was used, representing the standard scenario. We determined the cumulative positivity rate (PR) and the numbers of subjects diagnosed with advanced adenomas (N_AdvAd) and early stage CRC (N_earlyCRC) in the cohort over two rounds of screening (standard scenario) and compared it with hypothetical single-round screening with use of a lower cut-off and omission of the second round (alternative scenario).

Results

In the standard scenario, the cumulative (ie, round I and II combined) PR, N_AdvAd and N_earlyCRC were 13%, 180% and 26%, respectively. In alternative scenarios using a cut-off level of respectively ≥11 and ≥22 ng/HbmL buffer (corresponding to 2 and 4 µg Hb/g faeces), the PRs were 18% and 13%, the N_AdvAd were 180 and 162 and the N_earlyCRC ranged between 22–27 and 22–26.

Conclusions

The diagnostic yield of FIT screening using a lowered positivity threshold in combination with an extended screening interval (up to 5 years) may be similar to conventional FIT strategies. This justifies and motivates further research steps in this direction.
Magnetic and optical properties in the 1D TM–O chain compounds Sr2TMO3 (TM = Ni, Co): A first-principle investigation
Authors: Gui Hong , Li Xin , Zhao Zhenjie , Xie Wenhui
Published: March 2016

In this paper, we have calculated the structural, electronic, magnetic and optical properties of Sr2NiO3 and Sr2CoO3 using density functional theory (DFT) within generalized gradient approximation (GGA). The crystal structure of both materials is well described with Immm (No. 71) symmetry which are isostructural with Sr2CuO3 and both are quasi-one-dimensional (1D) rectangular lattice G-type antiferromagnets, in consistent with the experimental data.

Due to a distortion, Sr2CoO3 lifts the near-degeneracy [Formula: see text] and [Formula: see text] states of the local Co electronic configuration, which demonstrates a strong coupling between the structural lattice and the electronic configuration. The calculated band structure shows a band gap of 1.376 eV for Sr2NiO3 and a band gap of 1.735 eV for Sr2CoO3. Ni and Co ions are in the high-spin [Formula: see text] and [Formula: see text] configurations with the magnetic moments of 1.585 [Formula: see text] and 2.587 [Formula: see text], respectively. Based on the Heisenberg Hamiltonian model, we conclude that the superexchange intrachain TM–O–TM superexchange interaction is predominant and interaction between the 1D chains is weak. According to the calculated dielectric function, absorption spectrum and electron energy loss spectrum, the optical responses suggest that Sr2NiO3 shows the unique anisotropic structure and interaction of the application in optoelectronics.
Quantum radiation of Maxwell’s electromagnetic field in nonstationary Kerr–de Sitter black hole
Authors: Ibungochouba Singh T. , Ablu Meitei I. , Yugindro Singh K.
Published: March 2016

Quantum radiation properties of nonstationary Kerr–de Sitter (KdS) black hole is investigated using the method of generalized tortoise coordinate transformation. The locations of horizons and the temperature of the thermal radiation as well as the maximum energy of the nonthermal radiation are derived. It is found that the surface gravity and the Hawking temperature depend on both time and different angles. An extra coupling effect is obtained in the thermal radiation spectrum of Maxwell’s electromagnetic field equations which is absent in the thermal radiation spectrum of scalar particles. Further, the chemical potential derived from the thermal radiation spectrum of scalar particle has been found to be equal to the highest energy of the negative energy state of the scalar particle in the nonthermal radiation for KdS black hole. It is also shown that the generalized tortoise coordinate transformation produces a constant term in the expression of the surface gravity and Hawking temperature.
Multimodal biometrics for enhanced mobile device security
Authors: Gofman Mikhail I. , Mitra Sinjini , Cheng Tsu-Hsiang Kevin , Smith Nicholas T.
Published: March 2016

Fusing information from multiple biometric traits enhances authentication in mobile devices.
More encryption means less privacy
Authors: Kamp Poul-Henning
Published: March 2016

Retaining electronic privacy requires more political engagement.
Why logical clocks are easy
Authors: Baquero Carlos , Preguiça Nuno
Published: March 2016

Sometimes all you need is the right language.
The need for corporate diplomacy
Authors: Sako Mari
Published: March 2016

Whether global companies succeed or fail often depends on how effectively they develop and maintain cooperative relationships with other organizations and governments.
Automating proofs
Authors: Edwards Chris
Published: March 2016

Math struggles with the usability of formal proofs.
Search engine agendas
Authors: Anthes Gary
Published: March 2016

Is Google trying to trick you on the way to the polls?
A fistful of Bitcoins
Authors: Meiklejohn Sarah , Pomarole Marjori , Jordan Grant , Levchenko Kirill , McCoy Damon , Voelker Geoffrey M. , Savage Stefan
Published: March 2016

Bitcoin is a purely online virtual currency, unbacked by either physical commodities or sovereign obligation; instead, it relies on a combination of cryptographic protection and a peer-to-peer protocol for witnessing settlements. Consequently, Bitcoin has the unintuitive property that while the ownership of money is implicitly anonymous, its flow is globally visible. In this paper we explore this unique characteristic further, using heuristic clustering to group Bitcoin wallets based on evidence of shared authority, and then using re-identification attacks (i.e., empirical purchasing of goods and services) to classify the operators of those clusters. From this analysis, we consider the challenges for those seeking to use Bitcoin for criminal or fraudulent purposes at scale.
Cardiac hypertrophy and decreased high-density lipoprotein cholesterol in Lrig3-deficient mice
Authors: Hellström Martin , Ericsson Madelene , Johansson Bengt , Faraz Mahmood , Anderson Fredrick , Henriksson Roger , Nilsson Stefan K. , Hedman Håkan
Published: March 2016

Genetic factors confer risk for cardiovascular disease. Recently, large genome-wide population studies have shown associations between genomic loci close to LRIG3 and heart failure and plasma high-density lipoprotein (HDL) cholesterol level. Here, we ablated Lrig3 in mice and investigated the importance of Lrig3 for heart function and plasma lipid levels. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to analyze Lrig3 expression in the hearts of wild-type and Lrig3-deficient mice. In addition, molecular, physiological, and functional parameters such as organ weights, heart rate, blood pressure, heart structure and function, gene expression in the heart, and plasma insulin, glucose, and lipid levels were evaluated. The Lrig3-deficient mice were smaller than the wild-type mice but otherwise appeared grossly normal. Lrig3 was expressed at detectable but relatively low levels in adult mouse hearts. At 9 mo of age, ad libitum-fed Lrig3-deficient mice had lower insulin levels than wild-type mice. At 12 mo of age, Lrig3-deficient mice exhibited increased blood pressure, and the Lrig3-deficient female mice displayed signs of cardiac hypertrophy as assessed by echocardiography, heart-to-body weight ratio, and expression of the cardiac hypertrophy marker gene Nppa. Additionally, Lrig3-deficient mice had reduced plasma HDL cholesterol and free glycerol. These findings in mice complement the human epidemiological results and suggest that Lrig3 may influence heart function and plasma lipid levels in mice and humans.
Hypertension: the missing WNKs
Authors: Dbouk Hashem A. , Huang Chou-Long , Cobb Melanie H.
Published: March 2016

The With no Lysine [K] (WNK) family of enzymes are central in the regulation of blood pressure. WNKs have been implicated in hereditary hypertension disorders, mainly through control of the activity and levels of ion cotransporters and channels. Actions of WNKs in the kidney have been heavily investigated, and recent studies have provided insight into not only the regulation of these enzymes but also how mutations in WNKs and their interacting partners contribute to hypertensive disorders. Defining the roles of WNKs in the cardiovascular system will provide clues about additional mechanisms by which WNKs can regulate blood pressure. This review summarizes recent developments in the regulation of the WNK signaling cascade and its role in regulation of blood pressure.
Spatiotemporal distribution of location and object effects in the electromyographic activity of upper extremity muscles during reach-to-grasp
Authors: Rouse Adam G. , Schieber Marc H.
Published: March 2016

In reaching to grasp an object, proximal muscles that act on the shoulder and elbow classically have been viewed as transporting the hand to the intended location, while distal muscles that act on the fingers simultaneously shape the hand to grasp the object. Prior studies of electromyographic (EMG) activity in upper extremity muscles therefore have focused, by and large, either on proximal muscle activity during reaching to different locations or on distal muscle activity as the subject grasps various objects. Here, we examined the EMG activity of muscles from the shoulder to the hand, as monkeys reached and grasped in a task that dissociated location and object. We quantified the extent to which variation in the EMG activity of each muscle depended on location, on object, and on their interaction—all as a function of time. Although EMG variation depended on both location and object beginning early in the movement, an early phase of substantial location effects in muscles from proximal to distal was followed by a later phase in which object effects predominated throughout the extremity. Interaction effects remained relatively small. Our findings indicate that neural control of reach-to-grasp may occur largely in two sequential phases: the first, serving to project the entire upper extremity toward the intended location, and the second, acting predominantly to shape the entire extremity for grasping the object.
Fine and distributed subcellular retinotopy of excitatory inputs to the dendritic tree of a collision-detecting neuron
Authors: Zhu Ying , Gabbiani Fabrizio
Published: March 2016

Individual neurons in several sensory systems receive synaptic inputs organized according to subcellular topographic maps, yet the fine structure of this topographic organization and its relation to dendritic morphology have not been studied in detail. Subcellular topography is expected to play a role in dendritic integration, particularly when dendrites are extended and active. The lobula giant movement detector (LGMD) neuron in the locust visual system is known to receive topographic excitatory inputs on part of its dendritic tree. The LGMD responds preferentially to objects approaching on a collision course and is thought to implement several interesting dendritic computations. To study the fine retinotopic mapping of visual inputs onto the excitatory dendrites of the LGMD, we designed a custom microscope allowing visual stimulation at the native sampling resolution of the locust compound eye while simultaneously performing two-photon calcium imaging on excitatory dendrites. We show that the LGMD receives a distributed, fine retinotopic projection from the eye facets and that adjacent facets activate overlapping portions of the same dendritic branches. We also demonstrate that adjacent retinal inputs most likely make independent synapses on the excitatory dendrites of the LGMD. Finally, we show that the fine topographic mapping can be studied using dynamic visual stimuli. Our results reveal the detailed structure of the dendritic input originating from individual facets on the eye and their relation to that of adjacent facets. The mapping of visual space onto the LGMD's dendrites is expected to have implications for dendritic computation.
An Approach to Iron-Deficiency Anemia
Authors: Rasul Imran , Kandel Gabor P
Published: March 2016

Iron-deficiency anemia is a common reason for referral to a gastroenterologist. In adult men and postmenopausal women, gastrointestinal tract pathology is often the cause of iron-deficiency anemia, so patients are frequently referred for endoscopic evaluation. Endoscopy may be costly and at times difficult for the patient. Therefore, physicians need to know what lesions can be identified reliably and, more importantly, the importance of ruling out life-threatening conditions such as occult malignancy. Over the past decade, a number of prospective studies have been completed that examined the yield of endoscopy in the investigation of iron-deficiency anemia. The present article provides a broad overview of iron-deficiency anemia, with particular emphasis on hematological diagnosis, etiology, the use of endoscopy in identifying lesions and iron-repletion therapy. Other clinical scenarios, including assessment of patients on anti-inflammatory or anticoagulation therapy and patients with bleeding of obscure origin, are also addressed. The present article provides a diagnostic algorithm to iron-deficiency anemia, which describes a more systematic manner in which to approach iron-deficiency anemia.
Pathogenesis of Infectious Diarrhea
Authors: Stephen John
Published: March 2016

A brief overview of some of the main features involved in normal physiological bi-directional absorption and secretion of fluid in the gut is given, including the nature and cellular location of key enzymes, ion pumps, symports, antiports and diffusion channels; the microanatomy of intestinal villous vasculature and the dynamics of villus blood flow, which together generate hypertonic zones in villus tip regions; and the production, differentiation, escalator movement (from crypt to villus tip) and subsequent shedding of intestinal epithelial cells. (Neural and hormonal mechanisms that regulate normal mucosal ion transport are not discussed.) The manner in whichVibrio cholerae, several pathotypes ofEscherichia coli, severalSalmonellaserotypes, rotavirus,Campylobacterspecies,Shigella dysenteriae,Yersiniaspecies andClostridium difficileperturb these mechanisms and cause diarrhea, is discussed. Throughout the article, the main emphasis is on experimental studies designed to elucidate biological mechanisms and (where relevant) the microbial determinants responsible for diarrheal disease. Allusions are also made to the involvement of host responses such as the inflammatory response, the production and release of potent cytokines and accelerated homeostatic responses (such as increased rates of crypt cell division seen in some infections), and the role that they play in pathophysiological fluid secretion.
Splanchnic and Systemic Haemodynamic Derangement in Decompensated Cirrhosis
Authors: Møller Søren , Bendtsen Flemming , Henriksen Jens H
Published: March 2016

Patients with cirrhosis and portal hypertension exhibit characteristic hemodynamic changes with hyperkinetic systemic circulation, abnormal distribution of blood volume and neurohumoral dysregulation. Their plasma and noncentral blood volumes are increased. Splanchnic vasodilation is of pathogenic significance to the low systemic vascular resistance and abnormal volume distribution of blood, which are important elements in the development of the concomitant cardiac dysfunction, recently termed 'cirrhotic cardiomyopathy'. Systolic and diastolic functions are impaired with direct relation to the degree of liver dysfunction. Significant pathophysiological mechanisms are reduced beta-adrenergic receptor signal transduction, defective cardiac excitation-contraction coupling and conductance abnormalities. Vasodilators such as nitric oxide and calcitonin gene-related peptide are among the candidates in vasodilation and increased arterial compliance. Reflex-induced, enhanced sympathetic nervous system activity, activation of the renin-angiotensin aldosterone system, and elevated circulation vasopressin and endothelin-1 are implicated in hemodynamic counter-regulation in cirrhosis. Recent research has focused on the assertion that the hemodynamic and neurohumoral abnormalities in cirrhosis are part of a general cardiovascular dysfunction, influencing the course of the disease with the reduction of organ function, with sodium and water retention as the outcome. These aspects are relevant to therapy.
The Clinical Risks of Infection Associated with Endoscopy
Authors: Cowen Alistair E
Published: March 2016

The cleaning of flexible endoscopes is difficult and time consuming. Any method of attempted sterilization or high level disinfection will fail if prior cleaning has been defective. Inadequate reprocessing of endoscopes may result in patient to patient transmission of serious bacterial and viral diseases or infection with endemic hospital pathogens. Antibiotic prophylaxis is required to prevent septicemia and bacterial endocarditis in high risk patients undergoing specific endoscopic procedures. Prevention of serious endoscopy-associated clinical infections requires strict compliance with detailed reprocessing protocols by specially trained nursing staff.
Ranitidine bismuth citrate: A review
Authors: Chiba N , Hunt RH , Thomson ABR
Published: March 2016

Recognition of the relationship betweenHelicobacter pyloriinfection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications ofH pyloriinfection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicatingH pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice forH pylorieradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment ofH pyloriinfection. Bismuth levels do not appear to rise to toxic levels.
Patterns of Use of Flexible Sigmidoscopy, Colonoscopy and Gastroscopy: A Population‐Based Study in a Canadian Province
Authors: Hilsden Robert J
Published: March 2016

BACKGROUND & AIMS: Flexible sigmoidoscopy, colonoscopy and gastroscopy are important in the diagnosis and treatment of gastrointestinal (GI) diseases. Pressure on endoscopy resources is expected due to increased screening for GI cancers. The present study examined patterns of use of GI endoscopy in a Canadian province, Alberta, with universal health care insurance.

METHODS: Data on physician payments from January 1, 1994 to March 31, 2002 were used to calculate age‐sex adjusted rates and patterns of use.

RESULTS: The gastroscopy rate increased by 17%, from 9.7 (95% CI 9.6 to 9.9) to 10.3 (95% CI 10.1 to 10.5). The colonoscopy rate increased by 105%, from 4.8 (95% CI 4.6 to 5.0) to 9.8 (95% CI 9.6 to 10.1). Flexible sigmoidoscopy rates declined by 10%, from 4.68 (95% CI 4.56 to 4.80) to 4.21 (95% CI 4.11 to 4.32). The increase in colonoscopy rates occurred in all age groups, whereas gastroscopy rates increased only in the older age groups. Regional variation in procedure rates was evident, but rural health regions did not have consistently lower rates than the large urban regions. A polypectomy was performed on 23.7% of male patients and 15.4% of female patients at time of colonoscopy. Rates of polypectomy for individual endoscopists ranged from 0% to 60%.

CONCLUSIONS: There has been a marked increase in gastroscopy and colonoscopy rates, likely due to a broadening of indications rather than just increased use for cancer screening. Modest regional variation in rates exists, but there is no direct evidence of limited rural access to endoscopy. Reasonable polypectomy rates were seen but important variations between endoscopists exist.