bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualitative Interviewing: Testing Health Surveys Among Vietnam War Veterans at the Age of 70 Years
Authors: Fales April S. , Cypel Yasmin S. , Dunn Marsha E. , Truelove Ann L. , Ishii Erick K. , Schneiderman Aaron I. , Davey Victoria J.
Published: March 2019

The Vietnam Era Health Retrospective Observational Study (VE-HEROeS) is a nationwide study designed to compare the health of U.S. Vietnam era veterans to age- and sex-matched U.S. residents. Two self-administered mail questionnaires, one for veterans and the other for the U.S. nonmilitary population, were developed using already validated and newly developed items. A pretest was conducted to evaluate item recall and comprehension, new-item response validity, and the overall survey experience (usability of survey materials including the screener questionnaire for nonveterans). Subject recruitment was completed using convenience sampling and a $50 incentive. Cognitive interviewing and usability interviewing, two qualitative research methods, were implemented. Interviews were conducted in two stages (Stage 1, cognitive interviewing, n = 12; Stage 2, usability testing, n = 8) by three experienced methodologists. Concurrent probing techniques, unscripted probes, and retroactive probing were used to elicit response from 14 veterans and six nonveterans (mostly male, White, and aged 65-70 years). Information about the overall survey process was also obtained through observation during usability testing. Results signify that qualitative research is an important part of questionnaire development targeting older veterans due to issues involving comprehension, interpretability, and recall.
The Benefits of Immediate ART
Authors: Zhao Yan , McGoogan Jennifer M. , Wu Zunyou
Published: March 2019

The benefits of “early” antiretroviral therapy (ART; ie, initiation when CD4 ≥500 cells/mm3) are now well accepted as reflected in the removal of the CD4-based eligibility from new ART guidelines by the World Health Organization (WHO). However, neither the “treat-all” strategy recommendations presented in the guidelines nor the HIV care cascade goals in the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets adequately address the issue of ART timing. Our recent study on “immediate” ART (ie, ≤30 days after HIV diagnosis) adds important evidence demonstrating the real and meaningful benefits of rapid ART initiation even among those who have CD4 ≥500 cells/mm3. We call on WHO and UNAIDS to consider this research and encourage a shift from the treat-all strategy to an “immediately-treat-all” strategy, and from a slow, fragmented, complicated, multistep HIV care cascade to a fast, easy, and simple cascade with effectiveness measures that incorporate the important aspect of time.
Experienced Loneliness in Home-Based Rehabilitation: Perspectives of Older Adults With Disabilities and Their Health Care Professionals
Authors: Lykke Sine , Handberg Charlotte
Published: March 2019

This study aimed to describe and interpret perspectives of older adults with disabilities and their health care professionals (HCPs) on experienced loneliness during home-based rehabilitation. The interpretive description methodology guided the study. Data included semistructured individual interviews with seven older adults and a focus group interview with three HCPs. The analysis revealed four main findings that symbolized experienced loneliness. “Unspoken pain” and “gatekeeping emotions” concerning experienced loneliness as a taboo and stigma during rehabilitation were closely connected. “Resignation” and “awaiting company” signified the consequences of experienced loneliness when not addressed. Unspoken pain, gatekeeping emotions, resignation, and awaiting company were dominating experiences in the lives of the older adults during a home-based rehabilitation program following disability. This had restrained them from verbalizing and coping with loneliness during rehabilitation and life in general. The HCPs’ attempt to provide support for the older adults in coping with loneliness appeared to be characterized by gatekeeping emotions and keeping hidden agendas.
Solution-focused brief therapy to improve child well-being and family functioning outcomes with substance using parents in the child welfare system
Authors: Kim Johnny S. , Akin Becci A. , Brook Jody
Published: March 2019

This study examined the effectiveness of solution-focused brief therapy (SFBT) on child well-being and family functioning outcomes for child welfare involved parents. A randomized controlled trial design was used to evaluate the effectiveness of SFBT as compared to treatment-as-usual in an outpatient substance abuse treatment center. Mixed linear models tested within and between-group changes using intent-to-treat analysis ( N = 180). Hedges’s g effect sizes examined the magnitude of treatment effects. Both conditions reported improvements on the child well-being measures (Behavior Rating Inventory of Executive Function [BRIEF]-Parent Report and Child Behavior Checklist-School Age Form [CBCL-SA]) and family functioning measures (Adult-Adolescent Parenting Inventory [AAPI-2] and Center for Epidemiologic Studies-Depression [CES-D] Short Form) at posttest. While none of the between group analyses were statistically significant on either outcome domains, effect sizes did show improvements in the small to medium range for both groups. SFBT effect sizes for BRIEF subscales ranged from .024 to .267 and for control group ranged from .136 to .363. SFBT effect sizes on CBCL-SA subscales ranged from .059 to .321 and for control group ranged from .101 to .313. SFBT effect sizes on AAPI-2 subscales ranged from .006 to .620 and control group ranged from .023 to .624. SFBT effect sizes on CES-D measure were .428 and for control group were .317. Results show SFBT to be an effective intervention for helping parents around child well-being and family functioning outcomes similar to current empirically-supported therapies. SFBT provides a more strengths-based approach to help families improve family well-being and thus help improve their child’s well-being.
Girl Child Discrimination and Child Stunting in India: What Can be Done?
Authors: Nahar Shamsun , Pillai Vijayan K.
Published: March 2019

This study examines the extent of differences in the level of child stunting between boys and girls in India. Two explanations of the gap in stunting are tested using data from National Family Health Survey. Both log-linear and generalised ordinal regression methods were employed to analyse the data. The findings suggest a two-pronged approach to close the stunting gap: encouraging women’s education and improving sanitation through universal supply of toilet facilities and clean and portable water.
High risk of adverse pregnancy outcomes in women with a persistent lupus anticoagulant
Authors: Gebhart Johanna , Posch Florian , Koder Silvia , Quehenberger Peter , Perkmann Thomas , Kuessel Lorenz , Ay Cihan , Pabinger Ingrid
Published: March 2019

Lupus anticoagulant (LA) has been associated with pregnancy complications and pregnancy loss. Identification of predictive factors could aid in deciding on therapeutic management. To identify risk factors for adverse pregnancy outcomes in high-risk women with persistently positive LA, we prospectively followed 82 women of childbearing age, of whom 23 had 40 pregnancies within the Vienna Lupus Anticoagulant and Thrombosis Study. Pregnancy complications occurred in 28/40 (70%) pregnancies, including 22 (55%) spontaneous abortions (<10th week of gestation [WOG]: n = 12, 10th to 24th WOG: n = 10) and 6 deliveries <34th WOG (15%, 3 due to severe preeclampsia/HELLP [hemolysis, elevated liver enzymes, and a low platelet count] syndrome, 3 due to placental insufficiency). One abortion was followed by catastrophic antiphospholipid syndrome. Neither a history of pregnancy complications nor of thrombosis, or prepregnancy antiphospholipid antibody levels were associated with adverse pregnancy outcomes. In logistic regression analysis, higher age was associated with a lower risk of adverse pregnancy outcome (per 5 years’ increase: odds ratio [OR] = 0.41, 95% confidence interval [CI]: 0.19-0.87), a high Rosner index (index of circulating anticoagulant) predicted an increased risk (OR = 4.51, 95% CI: 1.08-18.93). Live birth rate was 15/28 (54%) in women on the combination of low-molecular-weight heparin and low-dose aspirin and 3/12 (25%) in those with no treatment or a single agent. We conclude that the risk of severe, even life-threatening pregnancy complications and adverse pregnancy outcomes is very high in women with persistent LA. A high Rosner index indicates an increased risk. Improved treatment options for women with persistently positive LA are urgently needed.
Glass confers rhabdomeric photoreceptor identity in Drosophila, but not across all metazoans
Authors: Bernardo-Garcia F. Javier , Syed Maryam , Jékely Gáspár , Sprecher Simon G.
Published: March 2019

Across metazoans, visual systems employ different types of photoreceptor neurons (PRs) to detect light. These include rhabdomeric PRs, which exist in distantly related phyla and possess an evolutionarily conserved phototransduction cascade. While the development of rhabdomeric PRs has been thoroughly studied in the fruit fly Drosophila melanogaster, we still know very little about how they form in other species. To investigate this question, we tested whether the transcription factor Glass, which is crucial for instructing rhabdomeric PR formation in Drosophila, may play a similar role in other metazoans. Glass homologues exist throughout the animal kingdom, indicating that this protein evolved prior to the metazoan radiation. Interestingly, our work indicates that glass is not expressed in rhabdomeric photoreceptors in the planarian Schmidtea mediterranea nor in the annelid Platynereis dumerilii. Combined with a comparative analysis of the Glass DNA-binding domain, our data suggest that the fate of rhabdomeric PRs is controlled by Glass-dependent and Glass-independent mechanisms in different animal clades.
Documentation of paintings restoration through photogrammetry and change detection algorithms
Authors: Abate Dante
Published: March 2019

The philosophical and theoretical foundations of the Theory of Restoration, envisioned by Cesare Brandi in 1975, are established around clear and straightforward guidelines on what is ethically acceptable, and unacceptable, in conservation. Specifically, the Italian scholar advocates for the complete reversibility of restoration work and respect for the history of an artwork. Indeed, according to these concepts, all interventions should be fully reversible so to return the object to its initial conditions without any damage. Bearing in mind these assumptions, a detailed documentation of all the steps of the conservation process, and the possibility to retrieve them a posteriori, must be considered essential. This concept especially applies when dealing with paintings restoration characterized by fine and small details. In recent years, the tendency is to favour minimal invasive interventions ranging from consolidation actions, cleaning samples, and colours retouching. Materials change more or less conspicuously over time according to their consistency and the intensity of the changing factors. Icons do not make an exception to this rule. This process affects the icon’s whole structure: the support, the painting itself and the varnish coating. This paper investigates the performance of change detection algorithms, developed in the remote sensing domain, and, in the framework of this research applied at a microscale (paintings). Each phase of the restoration process is documented exploiting a multi-epoch image acquisition. A monitoring methodology coupled with photogrammetry and 3D shape analysis is tested and described. It is anticipated that the proposed innovative use of change detection techniques can be applied to different kinds of painted surfaces. An icon, today preserved at the Byzantine Museum Makarios III Foundation in Nicosia and restored by the Department of Antiquities of Cyprus labs, has been used as a case study.
Suicide attempts and non-suicidal self-harm among university students: prevalence study
Authors: Sivertsen Børge , Hysing Mari , Knapstad Marit , Harvey Allison G. , Reneflot Anne , Lønning Kari Jussie , O'Connor Rory C.
Published: March 2019

Background

Suicide attempts and non-suicidal self-harm (NSSH) are major public health concerns that affect millions of young people worldwide. Consequently, there is a strong need for up-to-date epidemiological data in this population.

Aims

To provide prevalence and trend estimates of suicidal thoughts and behaviours and NSSH thoughts and behaviour in university students.

Method

Data are from a 2018 national health survey for higher education in Norway. A total of 50 054 full-time students (69.1% women) aged 18–35 years participated (response rate 31%). Suicidal ideation, suicide attempts and NSSH were assessed with three items drawn from the Adult Psychiatric Morbidity Survey, and thoughts of NSSH were assessed with one item from the Child and Adolescent Self-Harm in Europe study.

Results

Lifetime suicidal thoughts were reported by 21.0%, and 7.2% reported having such thoughts within the past year. In total, 4.2% reported a suicide attempt, of whom 0.4% reported attempting suicide within the past year. The prevalence of lifetime NSSH behaviour and thoughts was 19.6% and 22.6%, respectively. All four suicidal behaviour and NSSH variables were more common among students who were single, living alone and with a low annual income, as well as among immigrants. There was an increase in suicidal thoughts from 2010 (7.7%) to 2018 (11.4%), which was evident in both men and women.

Conclusions

The observed high and increasing prevalence of suicidal thoughts and NSSH among college and university students is alarming, underscoring the need for further research, preferably registry-linked studies, to confirm whether the reported prevalence is representative of the student population as a whole.

Declaration of interest

None.
Integrated care in mental health: next steps after the NHS Long Term Plan
Authors: Tracy Derek K. , Hanson Kara , Brown Tom , James Adrian J. B. , Paulsen Holly , Mulliez Zoé , Shergill Sukhwinder S.
Published: March 2019

Health and social care face growing and conflicting pressures: mounting complex needs of an ageing population, restricted funding and a workforce recruitment and retention crisis. In response, in the UK the NHS Long Term Plan promises increased investment and an emphasis on better ‘integrated’ care. We describe key aspects of integration that need addressing.

Declaration of interest

D.K.T. and S.S.S. are on the editorial board of the British Journal of Psychiatry and executives of the Academic Faculty at the Royal College of Psychiatrists. A.J.B.J., H.P. and Z.M. have roles at the Royal College of Psychiatrists that include evaluation of integrated care systems. A.J.B.J. is married to Dr Sarah Wollaston, Member of Parliament for Totnes and Chair of the Health Select Committee.
Liver Cancer in Guatemala: An Analysis of Mortality and Incidence Trends From 2012 to 2016
Authors: Kihn-Alarcón Alba J. , Toledo-Ponce María F. , Velarde Angel , Xu Ximing
Published: March 2019

PURPOSE

Guatemala has the highest mortality and incidence of liver cancer in Central and South America. The aim of this study is to describe the extent of liver cancer in the country from 2012 to 2016 and the associated risk factors.

METHODS

A secondary analysis was performed using liver cancer mortality and morbidity data and data on risk factors, such as hepatitis B virus infection, cirrhosis, and alcoholism.

RESULTS

Analysis revealed that liver cancer causes approximately 20% of cancer deaths in the country, is more frequent in the population older than age 65 years old, and is increasing in those age 30 to 44 years. More than 25% of deaths occurred in the North and West regions. The incidence of major risk factors for development of liver cancer has decreased.

CONCLUSION

The high mortality of liver cancer compared with its incidence indicates that most patients are diagnosed at late stages. To reduce the burden of liver cancer, creation of strategies for earlier detection is needed.
Sperm duct gland contents increase sperm velocity in the sand goby
Authors: Green Leon , Kvarnemo Charlotta
Published: March 2019

Sperm performance is often tightly linked to male reproductive success. In many demersal gobiid fishes, the male attaches sperm embedded in a mucus produced by sperm duct glands, to the nest substrate before spawning takes place. Sperm are activated as the mucus and other embedded gland contents dissolve into the water. To test the importance of gland content on sperm function in Pomatoschistus minutus, a marine fish with external fertilization, we used a paired experimental design, with spermatozoa tested with and without sperm duct gland contents mixed into seawater. We measured sperm velocity, percentage motile sperm and sperm viability over time. Sperm were found to swim 7.3% faster when gland contents were mixed in the seawater. Percentage motile sperm was unaffected by the gland contents. Sperm viability in seawater exceeded 24 h, but was unaffected by the gland contents. An increase in sperm velocity of similar magnitude as found here has been shown by others to increase reproductive success. Since velocity-boosting properties of sperm duct gland contents have now been found in three distantly related goby species, these traits may be conserved across the Gobiidae family and may aid in reproduction across a range of species and environments.
The 1ALCTL and 1BLCTL isoforms of Arg/Abl2 induce fibroblast activation and extra cellular matrix remodelling differently
Authors: Torsello Barbara , De Marco Sofia , Bombelli Silvia , Chisci Elisa , Cassina Valeria , Corti Roberta , Bernasconi Davide , Giovannoni Roberto , Bianchi Cristina , Perego Roberto A.
Published: March 2019

The fibrotic tissue and the stroma adjacent to cancer cells are characterised by the presence of activated fibroblasts (myofibroblasts) which play a role in creating a supportive tissue characterised by abundant extracellular matrix (ECM) secretion. The myofibroblasts remodel this tissue through secreted molecules and modulation of their cytoskeleton and specialized contractile structures. The non-receptor protein tyrosine kinase Arg (also called Abl2) has the unique ability to bind directly to the actin cytoskeleton, transducing diverse extracellular signals into cytoskeletal rearrangements. In this study we analysed the 1ALCTL and 1BLCTL Arg isoforms in Arg−/− murine embryonal fibroblasts (MEF) cell line, focusing on their capacity to activate fibroblasts and to remodel ECM. The results obtained showed that Arg isoform 1BLCTL has a major role in proliferation, migration/invasion of MEF and in inducing a milieu able to modulate tumour cell morphology, while 1ALCTL isoform has a role in MEF adhesion maintaining active focal adhesions. On the whole, the presence of Arg in MEF supports the proliferation, activation, adhesion, ECM contraction and stiffness, while the absence of Arg affected these myofibroblast features.

This article has an associated First Person interview with the first author of the paper.
Escort cell encapsulation ofDrosophilagermline cells is maintained by irre cell recognition module proteins
Authors: Ben-Zvi Doreen S. , Volk Talila
Published: March 2019

Differentiation of germline stem cells (GSCs) in the Drosophila ovary is induced by somatic escort cells (ECs), which extend membrane protrusions encapsulating the germline cells (GCs). Germline encapsulation requires activated epidermal growth factor receptor (Egfr) signaling within the ECs, following secretion of its ligands from the GCs. We show that the conserved family of irre cell recognition module (IRM) proteins is essential for GC encapsulation by ECs, with a requirement for roughest (rst) and kin of irre (kirre) in the germline and for sticks and stones (sns) and hibris (hbs) in ECs. In the absence of IRM components in their respective cell types, EC extensions are reduced concomitantly with a decrease in Egfr signaling in these cells. Reintroducing either activated Egfr in the ECs, or overexpressing its ligand Spitz (Spi) from the germline, rescued the requirement for IRM proteins in both cell types. These experiments introduce novel essential components, the IRM proteins, into the process of inductive interactions between GCs and ECs, and imply that IRM-mediated activity is required upstream of the Egfr signaling.
Simultaneous expression of ClopHensor and SLC26A3 reveals the nature of endogenous oxalate transport in CHO cells
Authors: Wasiluk Teresa , Roueinfar Mina , Hiryak Kayla , Torsiello Maria , Miner Alexander , Lee Jennifer , Venditto Michael , Terzaghi William , Lucent Del , VanWert Adam L.
Published: March 2019

ClopHensor, a fluorescent fusion protein, is a dual function biosensor that has been utilized as a tool for the simultaneous measurement of intracellular chloride and pH in cells. ClopHensor has traditionally been used in conjunction with fluorescence microscopy for single cell measurements. Here, we present a promising multi-well format advancement for the use of ClopHensor as a potential high-throughput method capable of measuring fluorescence signal intensity across a well of confluent cells with highly reproducible results. Using this system, we gained mechanistic insight into an endogenous oxalate transporter in Chinese hamster ovary (CHO) cells expressing ClopHensor and the human chloride transporter, SLC26A3. SLC26A3, a known anion exchanger, has been proposed to play a role in colonic oxalate absorption in humans. Our attempt to study the role of SLC26A3 in oxalate transport revealed the presence of an endogenous oxalate transporter in CHO cells. This transporter was strongly inhibited by niflumate, and exhibited clear saturability. Use of ClopHensor in a multi-well cell assay allowed us to quickly demonstrate that the endogenous oxalate transporter was unable to exchange chloride for bicarbonate, unlike SLC26A3.
bif1, a new BMP signaling inhibitor, regulates embryonic hematopoiesis in the zebrafish
Authors: Ghersi Joey J. , Mahony Christopher B. , Bertrand Julien Y.
Published: March 2019

Hematopoiesis maintains the entire blood system, and dysregulation of this process can lead to malignancies (leukemia), immunodeficiencies or red blood cell diseases (anemia, polycythemia vera). We took advantage of the zebrafish model that shares most of the genetic program involved in hematopoiesis with mammals to characterize a new gene of unknown function, si:ch73-299h12.2, which is expressed in the erythroid lineage during primitive, definitive and adult hematopoiesis. This gene, required during primitive and definitive erythropoiesis, encodes a C2H2 zinc-finger protein that inhibits BMP signaling. We therefore named this gene blood-inducing factor 1 and BMP inhibitory factor 1 (bif1). We identified a bif1 ortholog in Sinocyclocheilus rhinocerous, another fish, and in the mouse genome. Both genes also inhibit BMP signaling when overexpressed in zebrafish. In conclusion, we have deorphanized a new zebrafish gene of unknown function: bif1 codes for a zinc-finger protein that inhibits BMP signaling and also regulates primitive erythropoiesis and definitive hematopoiesis.
A branching gene regulatory network dictating different aspects of a neuronal cell identity
Authors: Stratmann Johannes , Ekman Helen , Thor Stefan
Published: March 2019

The nervous system displays a daunting cellular diversity. Neuronal subtypes differ from each other in several aspects, including their neurotransmitter expression and axon projection. These aspects can converge, but can also diverge, such that neurons expressing the same neurotransmitter may project axons to different targets. It is not well understood how regulatory programs converge/diverge to associate/dissociate different cell fate features. Studies of the Drosophila Tv1 neurons have identified a regulatory cascade, ladybird early→collier→apterous/eyes absent→dimmed, that specifies Tv1 neurotransmitter expression. Here, we conduct genetic and transcriptome analysis to address how other aspects of Tv1 cell fate are governed. We find that an initiator terminal selector gene triggers a feedforward loop that branches into different subroutines, each of which establishes different features of this one unique neuronal cell fate.
Organization and function of tension-dependent complexes at adherens junctions
Authors: Rauskolb Cordelia , Cervantes Estelle , Madere Ferralita , Irvine Kenneth D.
Published: March 2019

Adherens junctions provide attachments between neighboring epithelial cells and a physical link to the cytoskeleton, which enables them to sense and transmit forces and to initiate biomechanical signaling. Examination of the Ajuba LIM protein Jub in Drosophila embryos revealed that it is recruited to adherens junctions in tissues experiencing high levels of myosin activity, and that the pattern of Jub recruitment varies depending upon how tension is organized. In cells with high junctional myosin, Jub is recruited to puncta near intercellular vertices, which are distinct from Ena-containing puncta, but can overlap Vinc-containing puncta. We identify roles for Jub in modulating tension and cellular organization, which are shared with the cytohesin Step, and the cytohesin adapter Sstn, and show that Jub and Sstn together recruit Step to adherens junctions under tension. Our observations establish Jub as a reporter of tension experienced at adherens junctions, and identify distinct types of tension-dependent and tension-independent junctional complexes. They also identify a role for Jub in mediating a feedback loop that modulates the distribution of tension and cellular organization in epithelia.
Distinct functions of a cGMP-dependent protein kinase in nerve terminal growth and synaptic vesicle cycling
Authors: Dason Jeffrey S. , Allen Aaron M. , Vasquez Oscar E. , Sokolowski Marla B.
Published: March 2019

Sustained neurotransmission requires the tight coupling of synaptic vesicle (SV) exocytosis and endocytosis. The mechanisms underlying this coupling are poorly understood. We tested the hypothesis that a cGMP-dependent protein kinase (PKG), encoded by the foraging (for) gene in Drosophila melanogaster, is critical for this process using a for null mutant, genomic rescues and tissue-specific rescues. We uncoupled the exocytic and endocytic functions of FOR in neurotransmission using a temperature-sensitive shibire mutant in conjunction with fluorescein-assisted light inactivation of FOR. We discovered a dual role for presynaptic FOR, in which FOR inhibits SV exocytosis during low-frequency stimulation by negatively regulating presynaptic Ca2+ levels and maintains neurotransmission during high-frequency stimulation by facilitating SV endocytosis. Additionally, glial FOR negatively regulated nerve terminal growth through TGF-β signalling, and this developmental effect was independent of the effects of FOR on neurotransmission. Overall, FOR plays a critical role in coupling SV exocytosis and endocytosis, thereby balancing these two components to maintain sustained neurotransmission.
Behavioral responses of individual blue whales (Balaenoptera musculus) to mid-frequency military sonar
Authors: Southall Brandon L. , DeRuiter Stacy L. , Friedlaender Ari , Stimpert Alison K. , Goldbogen Jeremy A. , Hazen Elliott , Casey Caroline , Fregosi Selene , Cade David E. , Allen Ann N. , Harris Catriona M. , Schorr Greg , Moretti David , Guan Shane , Calambokidis John
Published: March 2019

This study measured the degree of behavioral responses in blue whales (Balaenoptera musculus) to controlled noise exposure off the southern California coast. High-resolution movement and passive acoustic data were obtained from non-invasive archival tags (n=42) whereas surface positions were obtained with visual focal follows. Controlled exposure experiments (CEEs) were used to obtain direct behavioral measurements before, during and after simulated and operational military mid-frequency active sonar (MFAS), pseudorandom noise (PRN) and controls (no noise exposure). For a subset of deep-feeding animals (n=21), active acoustic measurements of prey were obtained and used as contextual covariates in response analyses. To investigate potential behavioral changes within individuals as a function of controlled noise exposure conditions, two parallel analyses of time-series data for selected behavioral parameters (e.g. diving, horizontal movement and feeding) were conducted. This included expert scoring of responses according to a specified behavioral severity rating paradigm and quantitative change-point analyses using Mahalanobis distance statistics. Both methods identified clear changes in some conditions. More than 50% of blue whales in deep-feeding states responded during CEEs, whereas no changes in behavior were identified in shallow-feeding blue whales. Overall, responses were generally brief, of low to moderate severity, and highly dependent on exposure context such as behavioral state, source-to-whale horizontal range and prey availability. Response probability did not follow a simple exposure–response model based on received exposure level. These results, in combination with additional analytical methods to investigate different aspects of potential responses within and among individuals, provide a comprehensive evaluation of how free-ranging blue whales responded to mid-frequency military sonar.
Hyperspectral imaging as a tool for assessing coral health utilising natural fluorescence
Authors: Teague Jonathan , Willans Jack , Allen Michael , Scott Thomas , Day John
Published: March 2019

Fluorescent proteins are a crucial visualisation tool in a myriad of research fields including cell biology,
microbiology and medicine. Fluorescence is a result of the absorption of electromagnetic radiation at one wavelength and
its reemission at a longer wavelength. Coral communities exhibit a natural fluorescence which can be used to distinguish
between diseased and healthy specimens, however, current methods, such as the underwater visual census, are
expensive and time-consuming constituting many manned dive hours. We propose the use of a remotely operated vehicle
mounted with a novel hyperspectral fluorescence imaging (HyFI) “payload” for more rapid surveying and data collection.
We have tested our system in a laboratory environment on common coral species including Seriatopora spp., Montipora
verrucosa, Montipora spp., Montipora capricornis, Echinopora lamellose, Euphyllia ancora, Pocillopora damicornis and
Montipora confusa. With the aid of hyperspectral imaging, the coral specimens’ emission wavelengths can be accurately
assessed by capturing the emission spectra of the corals when excited with light emitting diodes (395–405 and 440 nm).
Fluorescence can also provide an indicator of coral bleaching as shown in our bleaching experiment where we observe
fluorescence reduction alongside coral bleaching.
Large hospital variation in the utilization of Post-procedural CT to detect pulmonary embolism/Deep Vein Thrombosis in Patients Undergoing Total Knee or Hip Replacement Surgery: Japanese Nationwide Diagnosis Procedure Combination Database Study
Authors: Kumamaru Kanako K. , Kumamaru Hiraku , Yasunaga Hideo , Matsui Hiroki , Omiya Toshinobu , Hori Masaaki , Suzuki Michimasa , Wada Akihiko , Kamagata Koji , Takamura Tomohiro , Irie Ryusuke , Nakanishi Atsushi , Aoki Shigeki
Published: March 2019

Objective:

The purpose of the study was to investigate variation in the use of in-hospital CT for venous thromboembolism (VTE) detection after total knee or hip replacement (TKR/THR) among surgical patients, using a nationwide Japanese in-hospital administrative database.

Methods:

This retrospective study using a national administrative database (4/2012–3/2013) extracted patients who underwent TKR/THR surgeries at hospitals meeting the annual case-volume threshold of ≥ 30. Hospitals were categorized into three equally sized groups by frequency of postoperative CT use (low, middle, and high CT use group) to compare baseline patient-level and hospital-level characteristics. To further investigate between-hospital variation in CT usage, we fitted a hierarchical logistic regression model including hospital-specific random intercepts and fixed patient- and hospital-level effects. The intra class correlation coefficient was used to measure the amount of variability in CT use attributable to between-hospital variation.

Results:

A total of 39,127 patients discharged from 447 hospitals met the inclusion criteria. The median hospital stay was 25 days (interquartile range, 20 – 32) and 7,599 (19.4%) patients underwent CT for VTE. CT utilization varied greatly among the hospitals; the crude frequency ranged from 0 to 100 % (median, 7.3 %; interquartile range, 1.8 – 18.3 %). After adjustment for known hospital- and patient-level factors related to CT use, 47 % of the variation in CT use remained attributable to the behavior of individual hospitals.

Conclusion:

We observed large inter hospital variability in the utilization of post-procedure CT for VTE detection in this Japanese TKR/THR cohort, suggesting that CT utilization is not optimized across the nation.

Advances in knowledge:

We observed significant variability in the utilization of post-procedure CT for VTE detection among inpatients who underwent TKR/THR surgeries in a large sample of Japanese hospitals. The large variation suggests that CT utilization is not optimized across the nation, and that there may be potential overutilization of the technology in the highest CT use hospitals.
Caucasian and south Asian men show equivalent improvements in surrogate biomarkers of cardiovascular and metabolic health following 6-weeks of supervised resistance training
Authors: Knox Allan , Sculthorpe Nicholas , Grace Fergal
Published: March 2019

Background: The South Asian population have greater cardiovascular risk than their age-matched Caucasian counterparts, characterized by unfavorable biomarkers. South Asians may also be partially resistant to the pleiotropic benefits of physical activity on cardiovascular health. There is a current absence of studies that compare markers of cardio-metabolic health between Caucasians and South Asians employing resistance exercise. This study set out to compare the response in biomarkers of cardio-metabolic health in Caucasians and South Asians in response to resistance exercise.

Methods: Caucasian (n=15, 25.5 ± 4.8 yrs) and South Asian (n=13, 25.4 ± 7.0 yrs) males completed a 6-week progressive resistance exercise protocol. Fasting blood glucose, insulin, and their product insulin resistance (HOMA-IR), triglycerides (TRIGS), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), vascular endothelial growth factor (VEGF), asymmetric dimythylarginine (ADMA), L-arginine (L-ARG) and C-reactive protein (CRP) were established at baseline and following resistance exercise.

Results: There were significant improvements in fasting glucose, TC, LDL, HDL and VEGF in both groups following resistance exercise (p<0.05, for all). No change was observed in insulin, HOMA-IR, TRIGS, ADMA, L-ARG following resistance exercise (p>0.05, in both groups). CRP increased in the South Asian group (p<0.05) but not the Caucasian group (p>0.05)

Conclusions: The cardio-metabolic response to resistance exercise is comparable in young Caucasian and South Asian males though inflammatory response to exercise may be prolonged in South Asians.
Targeting mu opioid receptors to modulate gastrointestinal function: what have we learnt so far from the studies in functional bowel disorders?
Authors: Corsetti Maura , Pannemans Jasper , Whorwell Peter
Published: March 2019

Opioids have recently received much attention because of the epidemic in their use in some countries such as the USA and the UK. Concerns have been raised about the possibility that they can increase mortality in patients when used on a long-term basis. Moreover, they are known to induce paradoxical hyperalgesia as well as alterations of gut function. The analgesic properties of opioids are mediated by receptors located in the brain, but as opioid receptors are also expressed in the gastrointestinal tract, new drugs acting on these receptors have recently been developed to treat two functional disorders, namely irritable bowel syndrome with diarrhoea and opioid-induced constipation. The aim of this article is to highlight some interesting observations resulting from the development of these drugs in the field of functional gastrointestinal disorders.
Recent advances in biomedical simulations: a manifesto for model engineering
Authors: Hellerstein Joseph L. , Gu Stanley , Choi Kiri , Sauro Herbert M.
Published: March 2019

Biomedical simulations are widely used to understand disease, engineer cells, and model cellular processes. In this article, we explore how to improve the quality of biomedical simulations by developing simulation models using tools and practices employed in software engineering. We refer to this direction as model engineering. Not all techniques used by software engineers are directly applicable to model engineering, and so some adaptations are required. That said, we believe that simulation models can benefit from software engineering practices for requirements, design, and construction as well as from software engineering tools for version control, error checking, and testing. Here we survey current efforts to improve simulation quality and discuss promising research directions for model engineering.
False signals induced by single-cell imputation
Authors: Andrews Tallulah S. , Hemberg Martin
Published: March 2019

Background: Single-cell RNA-seq is a powerful tool for measuring gene expression at the resolution of individual cells.  A challenge in the analysis of this data is the large amount of zero values, representing either missing data or no expression. Several imputation approaches have been proposed to address this issue, but they generally rely on structure inherent to the dataset under consideration they may not provide any additional information, hence, are limited by the information contained therein and the validity of their assumptions.

Methods: We evaluated the risk of generating false positive or irreproducible differential expression when imputing data with six different methods. We applied each method to a variety of simulated datasets as well as to permuted real single-cell RNA-seq datasets and consider the number of false positive gene-gene correlations and differentially expressed genes. Using matched 10X and Smart-seq2 data we examined whether cell-type specific markers were reproducible across datasets derived from the same tissue before and after imputation.

Results: The extent of false-positives introduced by imputation varied considerably by method. Data smoothing based methods, MAGIC, knn-smooth and dca, generated many false-positives in both real and simulated data. Model-based imputation methods typically generated fewer false-positives but this varied greatly depending on the diversity of cell-types in the sample. All imputation methods decreased the reproducibility of cell-type specific markers, although this could be mitigated by selecting markers with large effect size and significance.

Conclusions: Imputation of single-cell RNA-seq data introduces circularity that can generate false-positive results. Thus, statistical tests applied to imputed data should be treated with care. Additional filtering by effect size can reduce but not fully eliminate these effects. Of the methods we considered, SAVER was the least likely to generate false or irreproducible results, thus should be favoured over alternatives if imputation is necessary.
Chronic pain syndromes: overlapping phenotypes with common mechanisms
Authors: Littlejohn Geoffrey Owen , Guymer Emma
Published: March 2019

The common chronic pain syndromes of fibromyalgia, regional pain syndrome, and complex regional pain syndrome have been made to appear separate because they have been historically described by different groups and with different criteria, but they are really phenotypically accented expressions of the same processes triggered by emotional distress and filtered or modified by genetics, psychology, and local physical factors.
N-terminal pro-brain natriuretic peptide: a potential follow-up biomarker of mandibular advancement device efficacy on cardiac function in obstructive sleep apnea
Authors: Monneret Denis
Published: March 2019

Interrelationships between obstructive sleep apnea (OSA) and cardiovascular diseases are now recognized, but some underlying pathophysiological mechanisms remain controversial. Circulating cardiac biomarkers are diagnostic tools that can help understand them, in particular the N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of myocardial stretch, and a potential indicator of subclinical cardiac stress in OSA. Continuous positive airway pressure (CPAP), the first-line treatment of moderate to severe OSA, may be considered as uncomfortable, resulting in poor adherence, and reduced effectiveness. In this case, mandibular advancement devices (MAD) are an effective alternative therapy, more comfortable, and generally well accepted, with higher compliance. To date, few studies have compared the cardiovascular effects of CPAP and MAD. From recent literature reviews, it emerges that both therapies are effective in blood pressure reduction. However, the effects of MAD on other cardiovascular outcomes are conflicting, in particular as regards to its impact on circulating cardiac biomarkers. In a recent ancillary study from a randomized controlled trial, Recoquillonet alconcluded that two months of MAD treatment had no effect on NT-proBNP plasma levels in patients with severe OSA. The present discussion analyses this result from a biological, statistical, and analytical standpoint, in light of results from other studies evaluating natriuretic peptides in MAD-treated OSA, with the aim to support further longitudinal studies designed with a high methodological quality.
Hub genes in a pan-cancer co-expression network show potential for predicting drug responses
Authors: Azuaje Francisco , Kaoma Tony , Jeanty Céline , Nazarov Petr V. , Muller Arnaud , Kim Sang-Yoon , Dittmar Gunnar , Golebiewska Anna , Niclou Simone P.
Published: March 2019

Background: The topological analysis of networks extracted from different types of “omics” data is a useful strategy for characterizing biologically meaningful properties of the complex systems underlying these networks. In particular, the biological significance of highly connected genes in diverse molecular networks has been previously determined using data from several model organisms and phenotypes. Despite such insights, the predictive potential of candidate hubs in gene co-expression networks in the specific context of cancer-related drug experiments remains to be deeply investigated. The examination of such associations may offer opportunities for the accurate prediction of anticancer drug responses. 

Methods: Here, we address this problem by: a) analyzing a co-expression network obtained from thousands of cancer cell lines, b) detecting significant network hubs, and c) assessing their capacity to predict drug sensitivity using data from thousands of drug experiments. We investigated the prediction capability of those genes using a multiple linear regression model, independent datasets, comparisons with other models and our own in vitro experiments.

Results: These analyses led to the identification of 47 hub genes, which are implicated in a diverse range of cancer-relevant processes and pathways. Overall, encouraging agreements between predicted and observed drug sensitivities were observed in public datasets, as well as in our in vitro validations for four glioblastoma cell lines and four drugs. To facilitate further research, we share our hub-based drug sensitivity prediction model as an online tool.

Conclusions: Our research shows that co-expression network hubs are biologically interesting and exhibit potential for predicting drug responses in vitro. These findings motivate further investigations about the relevance and application of our unbiased discovery approach in pre-clinical, translationally-oriented research.
A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans
Authors: Byrne Claire S. , Blunt Dominic , Burn James , Chambers Edward , Dagbasi Aygul , Franco Becker Georgia , Gibson Glenn , Mendoza Lilian , Murphy Kevin , Poveda Carlos , Ramgulam Anya , Tashkova Martina , Walton Gemma , Washirasaksiri Chaiwat , Frost Gary
Published: March 2019

Introduction: A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract.

Methods: We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an in vitro continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets.

Registration: ISRCTN11327221.