bluuebunny/crossref_metadata_2025 huggingface dataset:
Helium ion beam induced growth of hammerhead AFM probes
Authors: Nanda Gaurav , van Veldhoven Emile , Maas Diederik , Sadeghian Hamed , Alkemade Paul F. A.
Published: November 2015

The authors report the direct-write growth of hammerhead atomic force microscope (AFM) probes by He+ beam induced deposition of platinum-carbon. In order to grow a thin nanoneedle on top of a conventional AFM probe, the authors move a focused He+ beam during exposure to a PtC precursor gas. In the final growth stage, a perpendicular movement of the beam results in the required three-dimensional (hammerhead) shape. The diameter of the needle depends on the ion beam dose, beam dwell time, and speed of the beam movement. A nanoneedle radius below 10 nm and a hammerhead smaller than 35 nm have been achieved. This fabrication process is robust and enables precise control over the three-dimensions of the hammerhead AFM probe. Finally, the authors test the capabilities of the fabricated AFM probes for two-dimensional metrology of sidewall angles and line-edge roughness of trenches and shark-fins in silicon.
Low-temperature sequential pulsed chemical vapor deposition of ternary BxGa1-xN and BxIn1-xN thin film alloys
Authors: Haider Ali , Kizir Seda , Ozgit-Akgun Cagla , Okyay Ali Kemal , Biyikli Necmi
Published: November 2015

In this work, the authors have performed sequential pulsed chemical vapor deposition of ternary BxGa1-xN and BxIn1-xN alloys at a growth temperature of 450 °C. Triethylboron, triethylgallium, trimethylindium, and N2 or N2/H2 plasma have been utilized as boron, gallium, indium, and nitrogen precursors, respectively. The authors have studied the compositional dependence of structural, optical, and morphological properties of BxGa1-xN and BxIn1-xN ternary thin film alloys. Grazing incidence X-ray diffraction measurements showed that boron incorporation in wurtzite lattice of GaN and InN diminishes the crystallinity of BxGa1-xN and BxIn1-xN sample. Refractive index decreased from 2.24 to 1.65 as the B concentration of BxGa1-xN increased from 35% to 88%. Similarly, refractive index of BxIn1-xN changed from 1.98 to 1.74 for increase in B concentration value from 32% to 87%, respectively. Optical transmission band edge values of the BxGa1-xN and BxIn1-xN films shifted to lower wavelengths with increasing boron content, indicating the tunability of energy band gap with alloy composition. Atomic force microscopy measurements revealed an increase in surface roughness with boron concentration of BxGa1-xN, while an opposite trend was observed for BxIn1-xN thin films.
Automated detection of Antarctic blue whale calls
Authors: Socheleau Francois-Xavier , Leroy Emmanuelle , Carvallo Pecci Andres , Samaran Flore , Bonnel Julien , Royer Jean-Yves
Published: November 2015

This paper addresses the problem of automated detection of Z-calls emitted by Antarctic blue whales (B. m. intermedia). The proposed solution is based on a subspace detector of sigmoidal-frequency signals with unknown time-varying amplitude. This detection strategy takes into account frequency variations of blue whale calls as well as the presence of other transient sounds that can interfere with Z-calls (such as airguns or other whale calls). The proposed method has been tested on more than 105 h of acoustic data containing about 2200 Z-calls (as found by an experienced human operator). This method is shown to have a correct-detection rate of up to more than 15% better than the extensible bioacoustic tool package, a spectrogram-based correlation detector commonly used to study blue whales. Because the proposed method relies on subspace detection, it does not suffer from some drawbacks of correlation-based detectors. In particular, it does not require the choice of an a priori fixed and subjective template. The analytic expression of the detection performance is also derived, which provides crucial information for higher level analyses such as animal density estimation from acoustic data. Finally, the detection threshold automatically adapts to the soundscape in order not to violate a user-specified false alarm rate.
Using individual differences to test the role of temporal and place cues in coding frequency modulation
Authors: Whiteford Kelly L. , Oxenham Andrew J.
Published: November 2015

The question of how frequency is coded in the peripheral auditory system remains unresolved. Previous research has suggested that slow rates of frequency modulation (FM) of a low carrier frequency may be coded via phase-locked temporal information in the auditory nerve, whereas FM at higher rates and/or high carrier frequencies may be coded via a rate-place (tonotopic) code. This hypothesis was tested in a cohort of 100 young normal-hearing listeners by comparing individual sensitivity to slow-rate (1-Hz) and fast-rate (20-Hz) FM at a carrier frequency of 500 Hz with independent measures of phase-locking (using dynamic interaural time difference, ITD, discrimination), level coding (using amplitude modulation, AM, detection), and frequency selectivity (using forward-masking patterns). All FM and AM thresholds were highly correlated with each other. However, no evidence was obtained for stronger correlations between measures thought to reflect phase-locking (e.g., slow-rate FM and ITD sensitivity), or between measures thought to reflect tonotopic coding (fast-rate FM and forward-masking patterns). The results suggest that either psychoacoustic performance in young normal-hearing listeners is not limited by peripheral coding, or that similar peripheral mechanisms limit both high- and low-rate FM coding.
AZD9150, a next-generation antisense oligonucleotide inhibitor of
STAT3
with early evidence of clinical activity in lymphoma and lung cancer
Authors: Hong David , Kurzrock Razelle , Kim Youngsoo , Woessner Richard , Younes Anas , Nemunaitis John , Fowler Nathan , Zhou Tianyuan , Schmidt Joanna , Jo Minji , Lee Samantha J. , Yamashita Mason , Hughes Steven G. , Fayad Luis , Piha-Paul Sarina , Nadella Murali V. P. , Mohseni Morvarid , Lawson Deborah , Reimer Corinne , Blakey David C. , Xiao Xiaokun , Hsu Jeff , Revenko Alexey , Monia Brett P. , MacLeod A. Robert
Published: November 2015

Systemically administered antisense oligonucleotide AZD9150 inhibits STAT3 and shows anticancer activity in preclinical models and patients.
The E3 ubiquitin ligase Idol controls brain LDL receptor expression, ApoE clearance, and Aβ amyloidosis
Authors: Choi Jinkuk , Gao Jie , Kim Jaekwang , Hong Cynthia , Kim Jungsu , Tontonoz Peter
Published: November 2015

Inhibiting the E3 ubiquitin ligase Idol in a mouse model of Alzheimer’s-like pathology ameliorates disease severity by promoting clearance of Aβ peptides by microglia.
Comment on “Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2”
Authors: Vassalli Anne , Li Sha , Tafti Mehdi
Published: November 2015

Hypocretin receptors are not autoreceptors to hypocretin neurons.
Africa’s leadership in biomedical research: Shifting the center of gravity
Authors: Kay Simon
Published: November 2015

The Wellcome Trust is shifting management of an initiative to train African research leaders to the continent itself.
Iron Modulates Butyrate Production by a Child Gut Microbiota
In Vitro
Authors: Dostal Alexandra , Lacroix Christophe , Bircher Lea , Pham Van Thanh , Follador Rainer , Zimmermann Michael Bruce , Chassard Christophe
Published: November 2015

The aim of this study was to investigate the effect of iron (Fe) availability on butyrate production in the complex bacterial ecosystem of the human gut. Hence, different Fe availabilities were mimicked in an
in vitro
colonic fermentation model (the polyfermenter intestinal model called PolyFermS) inoculated with immobilized gut microbiota from a child and in batch cultures of the butyrate producer
Roseburia intestinalis
. Shifts in the microbial community (16S rRNA sequencing and quantitative PCR), metabolic activity (high-performance liquid chromatography), and expression of genes involved in butyrate production were assessed. In the PolyFermS, moderate Fe deficiency resulted in a 1.4-fold increase in butyrate production and a 5-fold increase in butyryl-coenzyme A (CoA):acetate CoA-transferase gene expression, while very strong Fe deficiency significantly decreased butyrate concentrations and butyrate-producing bacteria compared with the results under normal Fe conditions. Batch cultures of
R. intestinalis
grown in a low-Fe environment preferentially produced lactate and had reduced butyrate and hydrogen production, in parallel with upregulation of the lactate dehydrogenase gene and downregulation of the pyruvate:ferredoxin-oxidoreductase gene. In contrast, under high-Fe conditions,
R. intestinalis
cultures showed enhanced butyrate and hydrogen production, along with increased expression of the corresponding genes, compared with the results under normal-Fe conditions. Our data reveal the strong regulatory effect of Fe on gut microbiota butyrate producers and on the concentrations of butyrate, which contributes to the maintenance of host gut health.

IMPORTANCE
Fe deficiency is one of the most common nutritional deficiencies worldwide and can be corrected by Fe supplementation. In this
in vitro
study, we show that environmental Fe concentrations in a continuous gut fermentation model closely mimicking a child's gut microbiota strongly affect the composition of the gut microbiome and its metabolic activity, particularly butyrate production. The differential expression of genes involved in the butyrate production pathway under different Fe conditions and the enzyme cofactor role of Fe explain the observed modulation of butyrate production. Our data reveal that the level of dietary Fe reaching the colon affects the microbiome, and its essential function of providing the host with beneficial butyrate.
RNA Futile Cycling in Model Persisters Derived from MazF Accumulation
Authors: Mok Wendy W. K. , Park Junyoung O. , Rabinowitz Joshua D. , Brynildsen Mark P.
Published: November 2015

Metabolism plays an important role in the persister phenotype, as evidenced by the number of strategies that perturb metabolism to sabotage this troublesome subpopulation. However, the absence of techniques to isolate high-purity populations of native persisters has precluded direct measurement of persister metabolism. To address this technical challenge, we studied
Escherichia coli
populations whose growth had been inhibited by the accumulation of the MazF toxin, which catalyzes RNA cleavage, as a model system for persistence. Using chromosomally integrated, orthogonally inducible promoters to express MazF and its antitoxin MazE, bacterial populations that were almost entirely tolerant to fluoroquinolone and β-lactam antibiotics were obtained upon MazF accumulation, and these were subjected to direct metabolic measurements. While MazF model persisters were nonreplicative, they maintained substantial oxygen and glucose consumption. Metabolomic analysis revealed accumulation of all four ribonucleotide monophosphates (NMPs). These results are consistent with a MazF-catalyzed RNA futile cycle, where the energy derived from catabolism is dissipated through continuous transcription and MazF-mediated RNA degradation. When transcription was inhibited, oxygen consumption and glucose uptake decreased, and nucleotide triphosphates (NTPs) and NTP/NMP ratios increased. Interestingly, the MazF-inhibited cells were sensitive to aminoglycosides, and this sensitivity was blocked by inhibition of transcription. Thus, in MazF model persisters, futile cycles of RNA synthesis and degradation result in both significant metabolic demands and aminoglycoside sensitivity.

IMPORTANCE
Metabolism plays a critical role in controlling each stage of bacterial persistence (shutdown, stasis, and reawakening). In this work, we generated an
E. coli
strain in which the MazE antitoxin and MazF toxin were artificially and independently inducible, and we used this strain to generate model persisters and study their metabolism. We found that even though growth of the model persisters was inhibited, they remained highly metabolically active. We further uncovered a futile cycle driven by continued transcription and MazF-mediated transcript degradation that dissipated the energy derived from carbon catabolism. Interestingly, the existence of this futile cycle acted as an Achilles’ heel for MazF model persisters, rendering them vulnerable to killing by aminoglycosides.
Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated Escherichia coli ST131 Clone
Authors: Forde Brian M. , Phan Minh-Duy , Gawthorne Jayde A. , Ashcroft Melinda M. , Stanton-Cook Mitchell , Sarkar Sohinee , Peters Kate M. , Chan Kok-Gan , Chong Teik Min , Yin Wai-Fong , Upton Mathew , Schembri Mark A. , Beatson Scott A.
Published: November 2015

Escherichia coli
sequence type 131 (ST131) is a clone of uropathogenic
E. coli
that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of
E. coli
EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three
m6
A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for
m6
A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located.

IMPORTANCE
DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant
E. coli
sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined
E. coli
clone.
Cryptococcus gattii in the Age of Whole-Genome Sequencing
Authors: Meyer Wieland
Published: November 2015

Cryptococcus gattii
, the sister species of
Cryptococcus neoformans
, is an emerging pathogen which gained importance in connection with the ongoing cryptococcosis outbreak on Vancouver Island. Many molecular studies have divided this species into for major lineages: VGI, VGII, VGIII, and VGIV. This commentary summarizes the whole-genome sequencing (WGS) studies that have been carried out with this species, re-emphasizing the phylogenetic relationships, showing chromosomal rearrangements between those four groups, and identifying VGII as ancestral population within
C. gattii
. In addition, WGS specific to VGII, containing the Vancouver Island outbreak genotypes and those from the Pacific Northwest region of the United States, has placed the origin of this lineage within South America and identified specific genes responsible for either brain or lung infection. It also showed, that many genotypes are spread across a number of different continents, as has been previously shown by multilocus sequence typing (MLST). In addition, it showed that recombination occurs more frequently between mitochondrial than nuclear genomes.
Posttranslational Modification of HOIP Blocks Toll-Like Receptor 4-Mediated Linear-Ubiquitin-Chain Formation
Authors: Bowman James , Rodgers Mary A. , Shi Mude , Amatya Rina , Hostager Bruce , Iwai Kazuhiro , Gao Shou-Jiang , Jung Jae U.
Published: November 2015

Linear ubiquitination is an atypical posttranslational modification catalyzed by the linear-ubiquitin-chain assembly complex (LUBAC), containing HOIP, HOIL-1L, and Sharpin. LUBAC facilitates NF-κB activation and inflammation upon receptor stimulation by ligating linear ubiquitin chains to critical signaling molecules. Indeed, linear-ubiquitination-dependent signaling is essential to prevent pyogenic bacterial infections that can lead to death. While linear ubiquitination is essential for intracellular receptor signaling upon microbial infection, this response must be measured and stopped to avoid tissue damage and autoimmunity. While LUBAC is activated upon bacterial stimulation, the mechanisms regulating LUBAC activity in response to bacterial stimuli have remained elusive. We demonstrate that LUBAC activity itself is downregulated through ubiquitination, specifically, ubiquitination of the catalytic subunit HOIP at the carboxyl-terminal lysine 1056. Ubiquitination of Lys1056 dynamically altered HOIP conformation, resulting in the suppression of its catalytic activity. Consequently, HOIP Lys1056-to-Arg mutation led not only to persistent LUBAC activity but also to prolonged NF-κB activation induced by bacterial lipopolysaccharide-mediated Toll-like receptor 4 (TLR4) stimulation, whereas it showed no effect on NF-κB activation induced by CD40 stimulation. This study describes a novel posttranslational regulation of LUBAC-mediated linear ubiquitination that is critical for specifically directing TLR4-mediated NF-κB activation.

IMPORTANCE
Posttranslational modification of proteins enables cells to respond quickly to infections and immune stimuli in a tightly controlled manner. Specifically, covalent modification of proteins with the small protein ubiquitin is essential for cells to initiate and terminate immune signaling in response to bacterial and viral infection. This process is controlled by ubiquitin ligase enzymes, which themselves must be regulated to prevent persistent and deleterious immune signaling. However, how this regulation is achieved is poorly understood. This paper reports a novel ubiquitination event of the atypical ubiquitin ligase HOIP that is required to terminate bacterial lipopolysaccharide (LPS)-induced TLR4 immune signaling. Ubiquitination causes the HOIP ligase to undergo a conformational change, which blocks its enzymatic activity and ultimately terminates LPS-induced TLR4 signaling. These findings provide a new mechanism for controlling HOIP ligase activity that is vital to properly regulate a proinflammatory immune response.
Cleidocranial dysplasia syndrome (CCD) with an unusual finding in a young patient
Authors: Singhal Parul , Singhal Anita , Jayam Cheranjeevi , Bandlapalli Anila
Published: November 2015

Cleidocranial dysplasia (CCD), an autosomal dominant disorder with a prevalence of 1 in 1 000 000 individuals, presents with a wide range of variability. Dentists are often the first to encounter patients with CCD, some of whom do not show typical manifestations. Since it has similar features to other pathologies, CCD is misdiagnosed as other conditions. A 10-year-old boy suffering from CCD was misdiagnosed as having rickets and was referred for non-eruption of a few permanent teeth along with an unaesthetic facial appearance. Clinically and radiologically, a diagnosis of CCD was made. Currently, management of this patient's orofacial manifestations is underway.
Presentation of cauda equina syndrome during labour
Authors: Jones Conor Stephen , Patel Salil , Griffiths-Jones William , Stokes Oliver M
Published: November 2015

Lumbar disc herniations are rare in pregnancy, with an incidence of 1:10 000. Less than 2% of these herniations result in cauda equina syndrome (CES). Diagnosing CES in pregnant patients can be difficult because changes in bladder and bowel habits are common in normal pregnancies. We present the case of a 29-year-old woman, with a history of lumbar radiculopathy, who presented at 39 weeks gestation with severe lower back and bilateral lower limb radiculopathy. Symptoms of CES began to develop only after the onset of labour. Diagnostic MRI was obtained following delivery and the patient was treated by microdiscectomy. Following surgery, bladder and bowel function began to normalise and at 3 months follow-up, she had made a full recovery. To the best of our knowledge, CES has never been reported to present during labour. This case highlights the diagnostic dilemma and need for a high index of suspicion.
Head injury patient with bilateral vocal cord paralysis: a mistake and a lesson learnt
Authors: Tomar Gaurav Singh , Kumar Niraj , Saxena Anudeep , Goyal Keshav
Published: November 2015

Bilateral recurrent nerve palsy along with head injury is a rare clinical possibility and can be potentially fatal if not properly diagnosed. We report a case of a head injury patient with intact Glasgow Coma Scale requiring immediate re-intubation and tracheostomy after extubation failure as a result of stridor and severe dyspnoea with paradoxical respiratory pattern, possibly because of undiagnosed significant surgical history.
Differential diagnosis of double site intussusception in childhood: a 15-year-old girl presenting with bowel obstruction
Authors: Davidson Joseph , Wright Naomi Jane , Kufeji Dorothy
Published: November 2015

Abdominal pain in a teenage girl is common; however, thorough history and examination can often distinguish a more rare or sinister diagnosis. We present a case of a 15-year-old girl presenting with abdominal pain, who was subsequently diagnosed with double intussusception secondary to her previously unrecognised Peutz-Jeghers syndrome (PJS).
Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement
Authors: Webborn Nick , Williams Alun , McNamee Mike , Bouchard Claude , Pitsiladis Yannis , Ahmetov Ildus , Ashley Euan , Byrne Nuala , Camporesi Silvia , Collins Malcolm , Dijkstra Paul , Eynon Nir , Fuku Noriyuki , Garton Fleur C , Hoppe Nils , Holm Søren , Kaye Jane , Klissouras Vassilis , Lucia Alejandro , Maase Kamiel , Moran Colin , North Kathryn N , Pigozzi Fabio , Wang Guan
Published: November 2015

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future.
What's in a name? The challenge of describing interventions in systematic reviews: analysis of a random sample of reviews of non-pharmacological stroke interventions
Authors: Hoffmann Tammy C , Walker Marion F , Langhorne Peter , Eames Sally , Thomas Emma , Glasziou Paul
Published: November 2015

Objective

To assess, in a sample of systematic reviews of non-pharmacological interventions, the completeness of intervention reporting, identify the most frequently missing elements, and assess review authors’ use of and beliefs about providing intervention information.

Design

Analysis of a random sample of systematic reviews of non-pharmacological stroke interventions; online survey of review authors.

Data sources and study selection

The Cochrane Library and PubMed were searched for potentially eligible systematic reviews and a random sample of these assessed for eligibility until 60 (30 Cochrane, 30 non-Cochrane) eligible reviews were identified.

Data collection

In each review, the completeness of the intervention description in each eligible trial (n=568) was assessed by 2 independent raters using the Template for Intervention Description and Replication (TIDieR) checklist. All review authors (n=46) were invited to complete a survey.

Results

Most reviews were missing intervention information for the majority of items. The most incompletely described items were: modifications, fidelity, materials, procedure and tailoring (missing from all interventions in 97%, 90%, 88%, 83% and 83% of reviews, respectively). Items that scored better, but were still incomplete for the majority of reviews, were: ‘when and how much’ (in 31% of reviews, adequate for all trials; in 57% of reviews, adequate for some trials); intervention mode (in 22% of reviews, adequate for all trials; in 38%, adequate for some trials); and location (in 19% of reviews, adequate for all trials). Of the 33 (71%) authors who responded, 58% reported having further intervention information but not including it, and 70% tried to obtain information.

Conclusions

Most focus on intervention reporting has been directed at trials. Poor intervention reporting in stroke systematic reviews is prevalent, compounded by poor trial reporting. Without adequate intervention descriptions, the conduct, usability and interpretation of reviews are restricted and therefore, require action by trialists, systematic reviewers, peer reviewers and editors.
Potential for the use of mHealth in the management of cardiovascular disease in Kerala: a qualitative study
Authors: Smith Rebecca , Menon Jaideep , Rajeev Jaya G , Feinberg Leo , Kumar Raman Krishan , Banerjee Amitava
Published: November 2015

Objectives

To assess the potential for using mHealth in cardiovascular disease (CVD) management in Kerala by exploring: (1) experiences and challenges of current CVD management; (2) current mobile phone use; (3) expectations of and barriers to mobile phone use in CVD management.

Design

Qualitative, semistructured, individual interviews.

Setting

5 primary health centres in Ernakulam district, Kerala, India.

Participants

15 participants in total from 3 stakeholder groups: 5 patients with CVD and/or its risk factors, 5 physicians treating CVD and 5 Accredited Social Health Activists (ASHAs). Patients were sampled for maximum variation on the basis of age, sex, CVD diagnoses and risk factors. All participants had access to a mobile phone.

Results

The main themes identified relating to the current challenges of CVD were poor patient disease knowledge, difficulties in implementing primary prevention and poor patient lifestyles. Participants noted phone calls as the main function of current mobile phone use. The expectations of mHealth use are to: improve accessibility to healthcare knowledge; provide reminders of appointments, medication and lifestyle changes; save time, money and travel; and improve ASHA job efficacy. All perceived barriers to mHealth were noted within physician interviews. These included fears of mobile phones negatively affecting physicians’ roles, the usability of mobile phones, radiation and the need for physical consultations.

Conclusions

There are three main potential uses of mHealth in this population: (1) as an educational tool, to improve health education and lifestyle behaviours; (2) to optimise the use of limited resources, by overcoming geographical barriers and financial constraints; (3) to improve use of healthcare, by providing appointment and treatment reminders in order to improve disease prevention and management. Successful mHealth design, which takes barriers into account, may complement current practice and optimise use of limited resources.
Reasons and remedies for under-representation of women in medical leadership roles: a qualitative study from Australia
Authors: Bismark Marie , Morris Jennifer , Thomas Laura , Loh Erwin , Phelps Grant , Dickinson Helen
Published: November 2015

Objective

To elicit medical leaders’ views on reasons and remedies for the under-representation of women in medical leadership roles.

Design

Qualitative study using semistructured interviews with medical practitioners who work in medical leadership roles. Interviews were transcribed verbatim and transcripts were analysed using thematic analysis.

Setting

Public hospitals, private healthcare providers, professional colleges and associations and government organisations in Australia.

Participants

30 medical practitioners who hold formal medical leadership roles.

Results

Despite dramatic increases in the entry of women into medicine in Australia, there remains a gross under-representation of women in formal, high-level medical leadership positions. The male-dominated nature of medical leadership in Australia was widely recognised by interviewees. A small number of interviewees viewed gender disparities in leadership roles as a ‘natural’ result of women's childrearing responsibilities. However, most interviewees believed that preventable gender-related barriers were impeding women's ability to achieve and thrive in medical leadership roles. Interviewees identified a range of potential barriers across three broad domains—perceptions of capability, capacity and credibility. As a counter to these, interviewees pointed to a range of benefits of women adopting these roles, and proposed a range of interventions that would support more women entering formal medical leadership roles.

Conclusions

While women make up more than half of medical graduates in Australia today, significant barriers restrict their entry into formal medical leadership roles. These constraints have internalised, interpersonal and structural elements that can be addressed through a range of strategies for advancing the role of women in medical leadership. These findings have implications for individual medical practitioners and health services, as well as professional colleges and associations.
Kazuo Ishiguro'sNever Let Me Go: a model of ‘completion’ for the end of life
Authors: Abrams Robert C
Published: November 2015

Kazuo Ishiguro's remarkable novel,Never Let Me Go, is a potent critique of societal and medical inhumanity. However, it can also read as a study of psychosocial development across the life span, featuring age-specific milestones and acceptance of death as the fixed point towards which humans advance through the stages of maturation. Emphasising a developmental perspective based on Eriksonian and Jaquesian theory, Ishiguro's storyline is followed closely and retold in this article. At each critical point in the novel, the differing styles of preparation for death are considered.
Do patients with ankylosing spondylitis adapt to their disease? Evidence from a ‘then-test’ in patients treated with TNF inhibitors
Authors: Essers Ivette , van Tubergen Astrid , Heldmann Frank , Baraliakos Xenofon , Braun Jürgen , Kiltz Uta , Boonen Annelies
Published: November 2015

Objective

To investigate whether patients with ankylosing spondylitis (AS) adapt to their disease, using the ‘then-test’.

Methods

Data from patients participating in the AS Study for Evaluation of Recombinant Infliximab Therapy (ASSERT) and continuing in the European AS Infliximab Cohort (EASIC) were used. At 5 assessments in EASIC, patients were asked to rerate their global well-being before the start of infliximab in ASSERT. The patients evaluated their past situation by using a ‘then-test’ (‘retrospective patient global’). Initial and retrospective patient global were compared using a paired t test, and mixed linear models investigated whether the retrospective score of well-being was stable at all follow-up assessments in EASIC. Linear regression analysis explored whether treatment response was associated with the difference between the initial and retrospective score (‘gap’) while adjusting for possible confounders.

Results

86 patients (mean age 39.8 years (SD=10.4), mean disease duration 10.8 years (SD=8.5)) contributed to the current analyses. At the time of starting infliximab, patients judged their global at 7.0 (SD=1.6), and with the ‘then-test’ at 7.2 (SD=2.3) (p=0.45). Time elapsed did not influence the ‘then-test’ (p=0.13). Multivariably, the gap was irrespective of treatment response, but associated with initial patient global (p<0.01) and initial Bath AS Disease Activity Index (p=0.02).

Conclusions

Patients with AS accurately judged their global well-being before starting treatment with tumour necrosis factor inhibition, even though substantial time had elapsed. The difference between initial and retrospective judgment was irrespective of treatment response. In this setting, the ‘then-test’ could not prove adaptation in AS.

Trial registration number

NCT01286545.
Neurotrophic growth factor responses to lower body resistance training in older adults
Authors: Walsh Jeremy J. , Scribbans Trisha D. , Bentley Robert F. , Kellawan J. Mikhail , Gurd Brendon , Tschakovsky Michael E.
Published: November 2015

Resistance exercise is an efficacious stimulus for improving cognitive function in older adults, which may be mediated by the upregulation of blood-borne neurotrophic growth factors (NTFs) like brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). However, the NTF response to resistance exercise and training in older adults is poorly understood. Therefore, the purpose of this study was to characterize the timing and magnitude of the NTF response following an acute bout of resistance exercise before and after 8 weeks of resistance training. Ten cognitively normal, older adults (ages 60–77 years, five men) were examined. The acute NTF response to resistance exercise was assessed via serum samples drawn at designated time points following exercise. This procedure was then repeated following 8 weeks of resistance training. BDNF increased immediately post-exercise (Δ9% pre-training, Δ11% post-training) then returned to resting levels while IGF-1 remained stable following resistance exercise before and after 8 weeks of resistance training. Basal levels of both NTFs were unaffected by the 8 week training period. We report a transient increase in serum BDNF following a bout of resistance exercise in older adults, which could have implications for the design of interventions seeking to maximize cognitive function in older adults.
Sorting and Selection with Imprecise Comparisons
Authors: Ajtai Miklós , Feldman Vitaly , Hassidim Avinatan , Nelson Jelani
Published: November 2015

We consider a simple model of imprecise comparisons: there exists some δ > 0 such that when a subject is given two elements to compare, if the values of those elements (as perceived by the subject) differ by at least δ, then the comparison will be made correctly; when the two elements have values that are within δ, the outcome of the comparison is unpredictable. This model is inspired by both imprecision in human judgment of values and also by bounded but potentially adversarial errors in the outcomes of sporting tournaments. Our model is closely related to a number of models commonly considered in the psychophysics literature where δ corresponds to the
Just Noticeable Difference (JND) unit
or
difference threshold
. In experimental psychology, the method of paired comparisons was proposed as a means for ranking preferences among
n
elements of a human subject. The method requires performing all (

n

2
) comparisons, then sorting elements according to the number of wins. The large number of comparisons is performed to counter the potentially faulty decision-making of the human subject, who acts as an imprecise comparator. We show that in our model the method of paired comparisons has optimal accuracy, minimizing the errors introduced by the imprecise comparisons. However, it is also wasteful because it requires all (

n

2
). We show that the same optimal guarantees can be achieved using 4
n
3/2
comparisons, and we prove the optimality of our method. We then explore the general tradeoff between the guarantees on the error that can be made and number of comparisons for the problems of sorting, max-finding, and selection. Our results provide strong lower bounds and close-to-optimal solutions for each of these problems.
Dynamic Reasoning Systems
Authors: Schwartz Daniel G.
Published: November 2015

A dynamic reasoning system (DRS) is an adaptation of a conventional formal logical system that explicitly portrays reasoning as a temporal activity, with each extralogical input to the system and each inference rule application being viewed as occurring at a distinct timestep. Every DRS incorporates some well-defined logic together with a controller that serves to guide the reasoning process in response to user inputs. Logics are generic, whereas controllers are application specific. Every controller does, nonetheless, provide an algorithm for nonmonotonic belief revision. The general notion of a DRS comprises a framework within which one can formulate the logic and algorithms for a given application and prove that the algorithms are correct, that is, that they serve to (1) derive all salient information and (2) preserve the consistency of the belief set. This article illustrates the idea with ordinary first-order predicate calculus, suitably modified for the present purpose, and two examples. The latter example revisits some classic nonmonotonic reasoning puzzles (Opus the Penguin, Nixon Diamond) and shows how these can be resolved in the context of a DRS, using an expanded version of first-order logic that incorporates typed predicate symbols. All concepts are rigorously defined and effectively computable, thereby providing the foundation for a future software implementation.
Handheld Visual Representation of a Castle Chapel Ruin
Authors: Madsen Jacob B. , Madsen Claus B.
Published: November 2015

We have experienced rapid development in Augmented Reality (AR) systems and platforms in the world of cultural heritage, namely in cultural settings and historical museums. However, we still face a range of challenges to design an AR system that meets the requirements for an AR installation working autonomously in a cultural heritage setting for an extended duration. This article describes the development of two installations for the visualization of a 3D reconstruction of a castle chapel, running autonomously during open hours in the location of a castle museum. We present a convincing 3D visualization running at interactive frame-rates on modern tablets. In one installation, the tablet is connected to a large screen TV for an immersive experience, and, in another, the tablet is hand-held, thus facilitating translational freedom in the chapel. Both installations allow unsupervised usage during museum visiting hours. Based on in-field observations and on-device logging of application usage, user behavior is analyzed and evaluated. Results indicate that users spent a limited amount of time using the application and did not fully explore the visual area of the chapel. In order for the user to spend more time with the application, additional information must be presented to the user.
Functional Circuitry of the Retina
Authors: Demb Jonathan B. , Singer Joshua H.
Published: November 2015

The mammalian retina is an important model system for studying neural circuitry: Its role in sensation is clear, its cell types are relatively well defined, and its responses to natural stimuli—light patterns—can be studied in vitro. To solve the retina, we need to understand how the circuits presynaptic to its output neurons, ganglion cells, divide the visual scene into parallel representations to be assembled and interpreted by the brain. This requires identifying the component interneurons and understanding how their intrinsic properties and synapses generate circuit behaviors. Because the cellular composition and fundamental properties of the retina are shared across species, basic mechanisms studied in the genetically modifiable mouse retina apply to primate vision. We propose that the apparent complexity of retinal computation derives from a straightforward mechanism—a dynamic balance of synaptic excitation and inhibition regulated by use-dependent synaptic depression—applied differentially to the parallel pathways that feed ganglion cells.
Angiogenesis and Eye Disease
Authors: Usui Yoshihiko , Westenskow Peter D. , Murinello Salome , Dorrell Michael I. , Scheppke Lea , Bucher Felicitas , Sakimoto Susumu , Paris Liliana P. , Aguilar Edith , Friedlander Martin
Published: November 2015

The retina consists of organized layers of photoreceptors, interneurons, glia, epithelial cells, and endothelial cells. The economic model of supply and demand used to appropriately determine cost is highly applicable to the retina, in which the extreme metabolic demands of phototransduction are met by precisely localized and designed vascular networks. Proper development and maintenance of these networks is critical to normal visual function; dysregulation is characteristic of several devastating human diseases, including but not limited to age-related macular degeneration and diabetic retinopathy. In this article, we focus on the lessons learned from the study of retinal vascular development and how these lessons can be used to better maintain adult vascular networks and prevent retinal diseases. We then outline the vasculotrophic contributions from neurons, retinal pigment epithelium (RPE) cells, and glia (specifically microglia) before we shift our focus to pathology to provide molecular contexts for neovascular retinal diseases. Finally, we conclude with a discussion that applies what we have learned about how retinal cells interact with the vasculature to identify and validate therapeutic approaches for neurovascular disease of the retina.
Visual Functions of the Thalamus
Authors: Usrey W. Martin , Alitto Henry J.
Published: November 2015

The thalamus is the heavily interconnected partner of the neocortex. All areas of the neocortex receive afferent input from and send efferent projections to specific thalamic nuclei. Through these connections, the thalamus serves to provide the cortex with sensory input, and to facilitate interareal cortical communication and motor and cognitive functions. In the visual system, the lateral geniculate nucleus (LGN) of the dorsal thalamus is the gateway through which visual information reaches the cerebral cortex. Visual processing in the LGN includes spatial and temporal influences on visual signals that serve to adjust response gain, transform the temporal structure of retinal activity patterns, and increase the signal-to-noise ratio of the retinal signal while preserving its basic content. This review examines recent advances in our understanding of LGN function and circuit organization and places these findings in a historical context.
p53 regulates expression of uncoupling protein 1 through binding and repression of PPARγ coactivator-1α
Authors: Hallenborg Philip , Fjære Even , Liaset Bjørn , Petersen Rasmus Koefoed , Murano Incoronata , Sonne Si Brask , Falkerslev Mathias , Winther Sally , Jensen Benjamin Anderschou Holbech , Ma Tao , Hansen Jacob B. , Cinti Saverio , Blagoev Blagoy , Madsen Lise , Kristiansen Karsten
Published: November 2015

The tumor suppressor p53 (TRP53 in mice) is known for its involvement in carcinogenesis, but work during recent years has underscored the importance of p53 in the regulation of whole body metabolism. A general notion is that p53 is necessary for efficient oxidative metabolism. The importance of UCP1-dependent uncoupled respiration and increased oxidation of glucose and fatty acids in brown or brown-like adipocytes, termed brite or beige, in relation to energy balance and homeostasis has been highlighted recently. UCP1-dependent uncoupled respiration in classic interscapular brown adipose tissue is central to cold-induced thermogenesis, whereas brite/beige adipocytes are of special importance in relation to diet-induced thermogenesis, where the importance of UCP1 is only clearly manifested in mice kept at thermoneutrality. We challenged wild-type and TRP53-deficient mice by high-fat feeding under thermoneutral conditions. Interestingly, mice lacking TRP53 gained less weight compared with their wild-type counterparts. This was related to an increased expression of Ucp1 and other PPARGC1a and PPARGC1b target genes but not Ppargc1a or Ppargc1b in inguinal white adipose tissue of mice lacking TRP53. We show that TRP53, independently of its ability to bind DNA, inhibits the activity of PPARGC1a and PPARGC1b. Collectively, our data show that TRP53 has the ability to regulate the thermogenic capacity of adipocytes through modulation of PPARGC1 activity.
Short-term muscle disuse lowers myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion
Authors: Wall Benjamin T. , Dirks Marlou L. , Snijders Tim , van Dijk Jan-Willem , Fritsch Mario , Verdijk Lex B. , van Loon Luc J. C.
Published: November 2015

Disuse leads to rapid loss of skeletal muscle mass and function. It has been hypothesized that short successive periods of muscle disuse throughout the lifespan play an important role in the development of sarcopenia. The physiological mechanisms underlying short-term muscle disuse atrophy remain to be elucidated. We assessed the impact of 5 days of muscle disuse on postabsorptive and postprandial myofibrillar protein synthesis rates in humans. Twelve healthy young (22 ± 1 yr) men underwent a 5-day period of one-legged knee immobilization (full leg cast). Quadriceps cross-sectional area (CSA) of both legs was assessed before and after immobilization. Continuous infusions of l-[ ring-2H5]phenylalanine and l-[1-13C]leucine were combined with the ingestion of a 25-g bolus of intrinsically l-[1-13C]phenylalanine- and l-[1-13C]leucine-labeled dietary protein to assess myofibrillar muscle protein fractional synthetic rates in the immobilized and nonimmobilized control leg. Immobilization led to a 3.9 ± 0.6% decrease in quadriceps muscle CSA of the immobilized leg. Based on the l-[ ring-2H5]phenylalanine tracer, immobilization reduced postabsorptive myofibrillar protein synthesis rates by 41 ± 13% (0.015 ± 0.002 vs. 0.032 ± 0.005%/h, P < 0.01) and postprandial myofibrillar protein synthesis rates by 53 ± 4% (0.020 ± 0.002 vs. 0.044 ± 0.003%/h, P < 0.01). Comparable results were found using the l-[1-13C]leucine tracer. Following protein ingestion, myofibrillar protein bound l-[1-13C]phenylalanine enrichments were 53 ± 18% lower in the immobilized compared with the control leg (0.007 ± 0.002 and 0.015 ± 0.002 mole% excess, respectively, P < 0.05). We conclude that 5 days of muscle disuse substantially lowers postabsorptive myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion.