bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal IP-10 Serum Levels Are Associated with the Course of Disease Activity and Remission in Patients with Rheumatoid Arthritis
Authors: van Hooij Anouk , Boeters Debbie M. , Tjon Kon Fat Elisa M. , van den Eeden Susan J. F. , Corstjens Paul L. A. M. , van der Helm-van Mil Annette H. M. , Geluk Annemieke
Published: June 2017

Although rheumatoid arthritis (RA) is a chronic, persistent autoimmune disease, 10 to 15% of RA patients achieve sustained disease-modifying antirheumatic drug (DMARD)-free remission over time. The biological mechanisms underlying the resolution of persistent inflammation in RA are still unidentified, and there is a lack of prognostic markers. It is well established that increased serum levels of gamma interferon-induced protein 10 (IP-10) are associated with (acute) increased inflammatory responses (e.g., in leprosy). In order to assess the potential of IP-10 as a diagnostic tool for inflammatory episodes of RA, we performed a retrospective study and assessed IP-10 levels in longitudinally banked serum samples obtained from patients upon first diagnosis of RA. The selection consisted of 15 persistent RA patients and 19 patients who achieved DMARD-free sustained remission. IP-10 levels, measured by use of a user-friendly quantitative lateral flow assay (LFA), showed up to 170-fold variation interindividually, and baseline IP-10 levels could not be differentiated between the two patient groups. However, a difference in the change in IP-10 levels between the first and last visits (ΔIP-10) was observed (
P
= 0.003) between DMARD-free (median ΔIP-10, −662 pg/ml [decrease]) and persistent (median ΔIP-10, 468 pg/ml [increase]) RA patients. Moreover, intraindividual changes in IP-10 levels during the course of disease corresponded to the disease activity score (DAS) (
P
= 0.05). These data indicate that IP-10 is associated with disease activity and perseverance of RA. The association of IP-10 with DAS indicates that this tool may be a practical diagnostic aid to help in monitoring disease progression in RA patients and may also find applications in other chronic diseases with exacerbated inflammatory episodes.
Evaluation of the Aptima HIV-1 Quant Dx Assay for HIV-1 RNA Quantitation in Different Biological Specimen Types
Authors: Yek Christina , Massanella Marta , Peling Tashi , Lednovich Kristen , Nair Sangeetha V. , Worlock Andrew , Vargas Milenka , Gianella Sara , Ellis Ronald J. , Strain Matthew C. , Busch Michael P. , Nugent C. Thomas , Richman Douglas D.
Published: June 2017

The search for a cure for HIV infection has highlighted the need for increasingly sensitive and precise assays to measure viral burden in various tissues and body fluids. We describe the application of a standardized assay for HIV-1 RNA in multiple specimen types. The fully automated Aptima HIV-1 Quant Dx assay (Aptima assay) is FDA cleared for blood plasma HIV-1 RNA quantitation. In this study, the Aptima assay was applied for the quantitation of HIV RNA in peripheral blood mononuclear cells (PBMCs;n= 72), seminal plasma (n= 20), cerebrospinal fluid (CSF;n= 36), dried blood spots (DBS;n= 104), and dried plasma spots (DPS;n= 104). The Aptima assay was equivalent to or better than commercial assays or validated in-house assays for the quantitation of HIV RNA in CSF and seminal plasma. For PBMC specimens, the sensitivity of the Aptima assay in the detection of HIV RNA decayed as background uninfected PBMC counts increased; proteinase K treatment demonstrated some benefit in restoring signal at higher levels of background PBMCs. Finally, the Aptima assay yielded 100% detection rates of DBS in participants with plasma HIV RNA levels of ≥35 copies/ml and 100% detection rates of DPS in participants with plasma HIV RNA levels of ≥394 copies/ml. The Aptima assay can be applied to a variety of specimens from HIV-infected subjects to measure HIV RNA for studies of viral persistence and cure strategies. It can also detect HIV in dried blood and plasma specimens, which may be of benefit in resource-limited settings.
Accurate and Rapid Differentiation of Acinetobacter baumannii Strains by Raman Spectroscopy: a Comparative Study
Authors: Ghebremedhin Meron , Heitkamp Rae , Yesupriya Shubha , Clay Bradford , Crane Nicole J.
Published: June 2017

In recent years, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has become the standard for routine bacterial species identification due to its rapidity and low costs for consumables compared to those of traditional DNA-based methods. However, it has been observed that strains of some bacterial species, such as
Acinetobacter baumannii
strains, cannot be reliably identified using mass spectrometry (MS). Raman spectroscopy is a rapid technique, as fast as MALDI-TOF, and has been shown to accurately identify bacterial strains and species. In this study, we compared hierarchical clustering results for MS, genomic, and antimicrobial susceptibility test data to hierarchical clustering results from Raman spectroscopic data for 31
A. baumannii
clinical isolates labeled according to their pulsed-field gel electrophoresis data for strain differentiation. In addition to performing hierarchical cluster analysis (HCA), multiple chemometric methods of analysis, including principal-component analysis (PCA) and partial least-squares discriminant analysis (PLSDA), were performed on the MS and Raman spectral data, along with a variety of spectral preprocessing techniques for best discriminative results. Finally, simple HCA algorithms were performed on all of the data sets to explore the relationships between, and natural groupings of, the strains and to compare results for the four data sets. To obtain numerical comparison values of the clustering results, the external cluster evaluation criteria of the Rand index of the HCA dendrograms were calculated. With a Rand index value of 0.88, Raman spectroscopy outperformed the other techniques, including MS (with a Rand index value of 0.58).
Time-Sampled Population Sequencing Reveals the Interplay of Selection and Genetic Drift in Experimental Evolution of
Potato Virus Y
Authors: Kutnjak Denis , Elena Santiago F. , Ravnikar Maja
Published: June 2017

RNA viruses are one of the fastest-evolving biological entities. Within their hosts, they exist as genetically diverse populations (i.e., viral mutant swarms), which are sculpted by different evolutionary mechanisms, such as mutation, natural selection, and genetic drift, and also the interactions between genetic variants within the mutant swarms. To elucidate the mechanisms that modulate the population diversity of an important plant-pathogenic virus, we performed evolution experiments with
Potato virus Y
(PVY) in potato genotypes that differ in their defense response against the virus. Using deep sequencing of small RNAs, we followed the temporal dynamics of standing and newly generated variations in the evolving viral lineages. A time-sampled approach allowed us to (i) reconstruct theoretical haplotypes in the starting population by using clustering of single nucleotide polymorphisms' trajectories and (ii) use quantitative population genetics approaches to estimate the contribution of selection and genetic drift, and their interplay, to the evolution of the virus. We detected imprints of strong selective sweeps and narrow genetic bottlenecks, followed by the shift in frequency of selected haplotypes. Comparison of patterns of viral evolution in differently susceptible host genotypes indicated possible diversifying evolution of PVY in the less-susceptible host (efficient in the accumulation of salicylic acid).

IMPORTANCE
High diversity of within-host populations of RNA viruses is an important aspect of their biology, since they represent a reservoir of genetic variants, which can enable quick adaptation of viruses to a changing environment. This study focuses on an important plant virus,
Potato virus Y
, and describes, at high resolution, temporal changes in the structure of viral populations within different potato genotypes. A novel and easy-to-implement computational approach was established to cluster single nucleotide polymorphisms into viral haplotypes from very short sequencing reads. During the experiment, a shift in the frequency of selected viral haplotypes was observed after a narrow genetic bottleneck, indicating an important role of the genetic drift in the evolution of the virus. On the other hand, a possible case of diversifying selection of the virus was observed in less susceptible host genotypes.
Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain
Authors: Mohanty Sanjib , Benjamin Laura A. , Majhi Megharay , Panda Premanand , Kampondeni Sam , Sahu Praveen K. , Mohanty Akshaya , Mahanta Kishore C. , Pattnaik Rajyabardhan , Mohanty Rashmi R. , Joshi Sonia , Mohanty Anita , Turnbull Ian W. , Dondorp Arjen M. , Taylor Terrie E. , Wassmer Samuel C.
Published: June 2017

The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by
Plasmodium falciparum
-infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions.
Surgical management of isolated mesenteric autoimmune disease: addressing the spectrum of IgG4-related disease and sclerosing mesenteritis
Authors: Greenbaum Alissa , Yadak Nour , Perez Steven , Rajput Ashwani
Published: June 2017

IgG4-related disease (IgG4-RD) is a rare form of autoimmune sclerosing disease, characterised by elevated serum IgG4and tissue IgG4levels, specific histopathological findings, multiorgan involvement and adequate response to glucocorticoid treatment. The low incidence and the heterogeneous nature of the disease has made consensus on diagnostic criteria for IgG4-RD difficult. Whether sclerosing mesenteritis (SM) is considered a manifestation of IgG4-RD is strongly debated. We present the case of a patient with a history of rheumatoid arthritis who presented with a calcified abdominal mass. She was found to have an isolated, pedunculated mesenteric mass positive for IgG4and concurrently elevated serum IgG4levels. Clinical features did not classify her disease as either SM or IgG4-RD as currently described in consensus statements. Concurrent diagnoses of IgG4-RD, SM and other autoimmune disorders, as well as postoperative recommendations for resected isolated IgG4-positive masses, are discussed.
Electrophysiological findings show generalised post-photoreceptoral deficiency in macular telangiectasia type 2
Authors: Ledolter Anna A , Holder Graham E , Ristl Robin , Schmidt-Erfurth Ursula , Ritter Markus
Published: June 2017

Background

Photoreceptor damage, reported in single observations, has been suggested to contribute to the disease pathogenesis in macular telangiectasia type 2 (MacTel2). The purpose of this study was to ascertain whether the photoreceptor or post-photoreceptoral function is affected in MacTel2 and could be detected using electrophysiological examination.

Methods

Thirty-five eyes from 18 patients (15 men, aged 60.1±9.6 years, range 38–77 years) with MacTel2 were included in the study. All patients underwent standard ophthalmic examination followed by pattern electroretinography (PERG) and full-field ERG. The data were compared against 22 normal control subjects (10 men, age 59.83±6.28 years, range 48–76).

Results

Mean PERG P50 amplitude and peak time in patients with MacTel2 did not differ significantly from control values (p>0.2) but P50 amplitude was subnormal in three patients. The mean scotopic rod b-wave amplitude was significantly lower in patients than in healthy controls (p=0.027). A lower dark-adapted 10.0 b-wave (p=0.06) but not a-wave amplitude (p=0.58) was present in patients with MacTel2. Photopic single-flash a-wave and b-wave amplitudes did not differ between patient and control groups (p=0.2 and 0.3), but 30 Hz flicker peak time was significantly later in patients with MacTel2 with no effect on amplitude (p=0.04 and 0.7).

Conclusion

Both scotopic (rod system dominated) and photopic ERGs (cone system) are consistent with post-photoreceptoral dysfunction. There was no electrophysiological evidence of dysfunction at the level of the photoreceptor.
Evaluating the short-term and long-term effects of an internet-based aural rehabilitation programme for hearing aid users in general clinical practice: a randomised controlled trial
Authors: Malmberg Milijana , Lunner Thomas , Kähäri Kim , Andersson Gerhard
Published: June 2017

Objective

Guided internet-based intervention beyond hearing aid (HA) fitting has been shown to be efficacious in randomised controlled trials (RCTs). However, internet interventions have rarely been applied clinically as a part of regular aural rehabilitation (AR). Our aim was to evaluate the effectiveness of internet-based AR for HA users from a clinical population.

Outcome measures

The Hearing Handicap Inventory for the Elderly (HHIE) was used as the primary outcome measure, and the Communication Strategies Scale (CSS) and the Hospital Anxiety and Depression Scale were used as secondary outcome measures. All questionnaires were administered before and directly after the intervention and at 6 months postintervention.

Methods

We used a parallel group design (RCT). The data were collected in 2013–2014 at three different clinics. Seventy-four HA users were randomly assigned to receive either full internet-based AR (intervention group, n=37) or one element of the internet-based AR (control group, n=37).

Results

Data were analysed following the intention-to-treat principle. Each group showed improved HHIE scores over time and did not differ significantly from each other. The intervention group showed significantly greater improvement compared with the control group for the CSS total and thenon-verbalsubscale scores. The intervention group and control group were also subdivided into two age groups: 20–59 years and 60–80 years. Significantly better improvement on the CSS total andnon-verbalsubscale scores was found in the older group compared with the younger participants.

Conclusions

This study indicates that participants in an internet-based intervention applied in general clinical practice showed improved self-reported communication skills compared with a control group. Receiving a full intervention was not more effective in improving self-reported hearing problems than receiving just one element of the internet-based intervention.

Trial registration number

This trial is registered at ClinicalTrals.gov,NCT01837550; results.
Impact of iron fortification on the geospatial patterns of malaria and non-malaria infection risk among young children: a secondary spatial analysis of clinical trial data from Ghana
Authors: Aimone Ashley M , Brown Patrick , Owusu-Agyei Seth , Zlotkin Stanley H , Cole Donald C
Published: June 2017

Objectives

Patterns of infection among children with varying levels of iron status in a malaria endemic area may vary spatially in ways requiring integrated infection and iron deficiency control programmes. The objective of this secondary analysis was to determine the geospatial factors associated with malaria and non-malaria infection status among young Ghanaian children at the end of a 5-month iron intervention trial.

Design

Cluster-randomised controlled trial.

Setting

Rural Ghana

Participants

1943 children (6–35 months of age) with geocoded compounds.

Interventions

Point-of-use fortification with micronutrient powders containing vitamins and minerals with or without iron.

Primary and secondary outcome measures

Generalised linear geostatistical models with a Matern spatial correlation function were used to analyse four infection response variables, defined using different combinations of inflammation (C-reactive protein, CRP >5 mg/L) and malaria parasitaemia. Analyses were also stratified by treatment group to assess the independent effects of the iron intervention.

Results

The by-group and combined-group analyses both showed that baseline infection status was the most consistent predictor of endline infection risk, particularly when infection was defined using parasitaemia. In the No-iron group, age above 24 months and weight-for-length z-score at baseline were associated with high CRP at endline. Higher asset score was associated with a 12% decreased odds of endline infection, defined as CRP >5 mg/L and/or parasitaemia (OR 0.88, 95% credible interval 0.78 to 0.98), regardless of group. Maps of the predicted risk and spatial random effects showed a defined low-risk area around the District centre, regardless of how infection was defined.

Conclusion

In a clinical trial setting of iron fortification, where all children receive treated bed nets and access to malaria treatment, there may be geographical variation in the risk of infection with distinct high-risk and low-risk areas, particularly around municipal centres.

Trial registration number

clinicaltrials.gov,NCT01001871.
Protocol for a randomised controlled trial of the effect of dapagliflozin, metformin and exercise on glycaemic variability, body composition and cardiovascular risk in prediabetes (the PRE-D Trial)
Authors: Færch Kristine , Amadid Hanan , Nielsen Lea Bruhn , Ried-Larsen Mathias , Karstoft Kristian , Persson Frederik , Jørgensen Marit Eika
Published: June 2017

Introduction

The primary aim of this study is to compare the efficacy of three short-term glucose-lowering interventions (exercise, metformin and dapagliflozin) on glycaemic variability in overweight or obese men and women with elevated diabetes risk (ie, prediabetes, defined as haemoglobin A1c(HbA1c)39–47 mmol/mol / 5.7%–6.4%). The secondary aims are to investigate the effects of the interventions on body composition and cardiometabolic risk factors.

Methods and analysis

The Pre-D Trial is an investigator-initiated, randomised, controlled, parallel, open-label, superiority trial. The study aims to assign 120 participants in a 1:1:1:1 ratio to receive one of four interventions for 13 weeks: (1) dapagliflozin (10 mg once daily); (2) metformin (850 mg twice daily); (3) exercise (interval training, 5 days a week, 30 min per session); or (4) control (lifestyle advice). After the 13 weeks of intervention, a follow-up period of 13 weeks will follow to study the long-term effects of the interventions. The primary endpoint is reduction from baseline to end-of treatment (13 weeks) in mean amplitude of glycaemic excursions measured by continuous glucose monitoring. The secondary endpoints include concomitant changes in various measures of glucose metabolism, body weight, cardiorespiratory fitness, blood pressure, plasma lipids, objectively measured physical activity and dietary intake.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee of the Capital Region and the Danish Medicines Agency. Approval of data and biobank storage has been obtained from the Danish Data Protection Board. The study will be carried out according to the Declaration of Helsinki and to the regulations for good clinical practice. The results from this trial will allow a number of research questions concerning the effect of exercise versus dapagliflozin or metformin in HbA1c-defined prediabetes to be addressed.

Trial registration

NCT02695810
Dyspnoea-12: a translation and linguistic validation study in a Swedish setting
Authors: Sundh Josefin , Ekström Magnus
Published: June 2017

Background

Dyspnoea consists of multiple dimensions including the intensity, unpleasantness, sensory qualities and emotional responses which may differ between patient groups, settings and in relation to treatment. The Dyspnoea-12 is a validated and convenient instrument for multidimensional measurement in English. We aimed to take forward a Swedish version of the Dyspnoea-12.

Methods

The linguistic validation of the Dyspnoea-12 was performed (Mapi Language Services, Lyon, France). The standardised procedure involved forward and backward translations by three independent certified translators and revisions after feedback from an in-country linguistic consultant, the developerand three native physicians. The understanding and convenience of the translated version was evaluated using qualitative in-depth interviews with five patients with dyspnoea.

Results

A Swedish version of the Dyspnoea-12 was elaborated and evaluated carefully according to international guidelines. The Swedish version, ‘Dyspné−12’, has the same layout as the original version, including 12 items distributed on seven physical and five affective items. The Dyspnoea-12 is copyrighted by the developer but can be used free of charge after permission for not industry-funded research.

Conclusion

A Swedish version of the Dyspnoea-12 is now available for clinical validation and multidimensional measurement across diseases and settings with the aim of improved evaluation and management of dyspnoea.
A cross-sectional study measuring vanadium and chromium levels in paediatric patients with CKD
Authors: Filler Guido , Kobrzynski Marta , Sidhu Hargun Kaur , Belostotsky Vladimir , Huang Shih-Han S , McIntyre Chris , Yang Liju
Published: June 2017

Objectives

Although many secondary effects of high levels of vanadium (V) and chromium (Cr) overlap with symptoms seen in paediatric patients with chronic kidney disease (CKD), their plasma V and Cr levels are understudied.

Design

Ancillary cross-sectional study to a prospective, longitudinal, randomised controlled trial.

Setting

Children’s Hospital of Western Ontario, London Health Sciences Centre, London, Ontario, Canada.

Participants

36 children and adolescents 4–18 years of age with CKD.

Interventions

1–6 trace element measurements per patient. Cystatin C (CysC) estimated glomerular filtration rate (eGFR) was calculated using the Filler formula. Plasma V and Cr levels were measured using high-resolution sector field inductively coupled mass spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart programme. Water Cr and V data were obtained from the Ontario Water (Stream) Quality Monitoring Network.

Primary and secondary outcome measures

Primary outcomes: plasma Cr and V. Secondary outcomes: age, season, CysC, CysC eGFR, and Cr and V levels in environmental water.

Results

The median (IQR) eGFR was 51 mL/min/1.73 m2(35, 75). The median V level was 0.12 µg/L (0.09, 0.18), which was significantly greater than the 97.5th percentile of the reference interval of 0.088 µg/L; 32 patients had at least one set of V levels above the published reference interval. The median Cr level was 0.43 µg/L (0.36, 0.54), which was also significantly greater than the established reference interval; 34 had at least one set of Cr levels above the published reference interval. V and Cr levels were moderately correlated. Only some patients had high environmental exposure.

Conclusions

Our study suggests that paediatric patients with CKD have elevated plasma levels of V and Cr. This may be the result of both environmental exposure and a low eGFR. It may be necessary to monitor V and Cr levels in patients with an eGFR <30 mL/min/1.73 m2.

Trial registration number

NCT02126293; HC#172241.
Patient-reported outcome measures (PROMs) for assessing perceived listening effort in hearing loss: protocol for a systematic review
Authors: Hughes Sarah E , Rapport Frances L , Boisvert Isabelle , McMahon Catherine M , Hutchings Hayley A
Published: June 2017

Introduction

In the UK, it is estimated that a disabling hearing loss (HL) affects 1 in 6 people. HL has functional, economic and social-emotional consequences for affected individuals. Intervention for HL focuses on improving access to the auditory signal using hearing aids or cochlear implants. However, even if sounds are audible and speech is understood, individuals with HL often report increased effort when listening.

Listening effort (LE) may be measured using self-reported measures such as patient-reported outcome measures (PROMs). PROMs are validated questionnaires completed by patients to measure their perceptions of their own functional status and well-being. When selecting a PROM for use in research or clinical practice, it is necessary to appraise the evidence of a PROM’s acceptability to patients, validity, responsiveness and reliability.

Methods and analysis

A systematic review of studies evaluating the measurement properties of PROMs available to measure LE in HL will be undertaken. MEDLINE, EMBASE, CINAHL, PsychINFO and Web of Science will be searched electronically. Reference lists of included studies, key journals and the grey literature will be hand-searched to identify further studies for inclusion. Two reviewers will independently complete title, abstract and full-text screening to determine study eligibility. Data on the characteristics of each study and each PROM will be extracted. Methodological quality of the included studies will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, the quality of included PROMs appraised and the credibility of the evidence assessed. A narrative synthesis will summarise extracted data.

Ethics and dissemination

Ethical permission is not required, as this study uses data from published research. Dissemination will be through publication in peer-reviewed journals, conference presentations and the lead author’s doctoral dissertation. Findings may inform the selection of PROMs used to measure LE in HL.
The eSMART study protocol: a randomised controlled trial to evaluate electronic symptom management using the advanced symptom management system (ASyMS) remote technology for patients with cancer
Authors: Maguire Roma , Fox Patricia A , McCann Lisa , Miaskowski Christine , Kotronoulas Grigorios , Miller Morven , Furlong Eileen , Ream Emma , Armes Jo , Patiraki Elisabeth , Gaiger Alexander , Berg Geir V , Flowerday Adrian , Donnan Peter , McCrone Paul , Apostolidis Kathi , Harris Jenny , Katsaragakis Stylianos , Buick Alison R , Kearney Nora
Published: June 2017

Introduction

While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients, overall, these studies have significant methodological weaknesses. The electronic Symptom Management using the Advanced Symptom Management System (ASyMS) Remote Technology (eSMART) study is designed to specifically address these weaknesses with an appropriately powered, repeated-measures, parallel-group stratified randomised controlled trial of oncology patients.

Methods and analysis

A total of 1108 patients scheduled to commence first-line chemotherapy (CTX) for breast, colorectal or haematological cancer will be recruited from multiple sites across five European countries.

Patients will be randomised (1:1) to the ASyMS intervention (intervention group) or to standard care currently available at each site (control group). Patients in the control and intervention groups will complete a demographic and clinical questionnaire, as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment, after each of their CTX cycles (up to a maximum of six cycles) and at 3, 6, 9 and 12 months after completion of their sixth cycle of CTX. Outcomes that will be assessed include symptom burden (primary outcome), quality of life, supportive care needs, anxiety, self-care self-efficacy, work limitations and cost effectiveness and, from a health professional perspective, changes in clinical practice (secondary outcomes).

Ethics and dissemination

Ethical approval will be obtained prior to the implementation of all major study amendments. Applications will be submitted to all of the ethics committees that granted initial approval.

eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries. In collaboration with the European Cancer Patient Coalition (ECPC), the trial results will be disseminated through publications in scientific journals, presentations at international conferences, and postings on the eSMART website and other relevant clinician and consumer websites; establishment of an eSMART website (www.esmartproject.eu) with publicly accessible general information; creation of an eSMART Twitter Handle, and production of a toolkit for implementing/utilising the ASyMS technology in a variety of clinical practices and other transferable health care contexts.

Trial registration number

NCT02356081.
Attitudes and behaviours of adolescents towards antibiotics and self-care for respiratory tract infections: a qualitative study
Authors: Hawking Meredith KD , Lecky Donna M , Touboul Lundgren Pia , Aldigs Eman , Abdulmajed Hind , Ioannidou Eleni , Paraskeva-Hadjichambi Demetra , Khouri Pauline , Gal Micaela , Hadjichambis Andreas Ch. , Mappouras Demetrios , McNulty Cliodna AM
Published: June 2017

Background

To understand attitudes and behaviours of adolescents towards antibiotics, antimicrobial resistance and respiratory tract infections.

Design

Qualitative approach informed by the Theory of Planned Behaviour. Semi-structured interviews and focus groups were undertaken. We aimed to inform the development of an intervention in an international setting to improve antibiotic use among adolescents; therefore on completion of thematic analysis, findings were triangulated with qualitative data from similar studies in France, Saudi Arabia and Cyprus to elucidate differences in the behaviour change model and adaptation to diverse contexts.

Setting

7 educational establishments from the south of England.

Participants

53 adolescents (16–18 years) participated in seven focus groups and 21 participated in interviews.

Results

Most participants had taken antibiotics and likened them to other common medications such as painkillers; they reported that their peers treat antibiotics like a ‘cure-all’ and that they themselves were not interested in antibiotics as a discussion topic. They demonstrated low knowledge of the difference between viral and bacterial infections.Participants self-cared for colds and flu but believed antibiotics are required to treat other RTIs such as tonsillitis, which they perceived as more ‘serious’. Past history of taking antibiotics for RTIs instilled the belief that antibiotics were required for future RTIs. Those who characterised themselves as ‘non-science students’ were less informed about antibiotics and AMR. Most participants felt that AMR was irrelevant to them and their peers. Some ‘non-science’ students thought resistance was a property of the body, rather than bacteria.

Conclusion

Addressing adolescents’ misperceptions about antibiotics and the treatment of RTIs using a behaviour change intervention should help improve antibiotic awareness and may break the cycle of patient demand for antibiotics to treat RTIs amongst this group. Schools should consider educating all students in further education about antibiotic usage and AMR, not only those taking science.
The STOP-AB trial protocol: efficacy and safety of discontinuing patient antibiotic treatment when physicians no longer consider it necessary
Authors: Llor Carl , Moragas Ana , Bayona Carolina , Cots Josep M , Molero José M , Ribas Joana , Fóthy Julio Francisco , Gutiérrez Isabel , Sánchez Coro , Ortega Jesús , Arranz Javier , Botanes Jenifer , Robles Purificación
Published: June 2017

Introduction

Since 2011, the Spanish Society of Family Medicine has recommended general practitioners (GPs) to ask their patients to stop taking antibiotics when they suspect a viral infection. However, this practice is seldom used because uncertainty about diagnosis, and fear of consequences of discontinuing antibiotic therapy, as well as perceived pressure to continue prescribing antibiotics and potential conflict with patients are more of a concern for GPs than antibiotic resistance. The main objective of this study is to determine whether discontinuation of antibiotic therapy when a GP no longer considers it necessary has any impact on the number of days with severe symptoms.

Methods and analysis

This is a multicentre, open-label, randomised controlled clinical trial. The study was conducted in 10 primary care centres in Spain. We included patients from 18 to 75 years of age with uncomplicated acute respiratory tract infections—acute rhinosinusitis, acute sore throat, influenza or acute bronchitis—who had previously taken any dose of antibiotic for <3 days, which physicians no longer considered necessary. The patients were randomly assigned to the usual strategy of continuing antibiotic treatment or to discontinuing antibiotic therapy. A sample size of 240 patients per group was calculated on the basis of a reduction of 1 day in the duration of severe symptoms being a clinically relevant outcome. The primary outcome was the duration of severe symptoms, that is, symptoms scored 5 or 6 by means of validated symptom diaries. Secondary outcomes included antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months.

Ethics and dissemination

The study was approved by the Ethical Board ofFundació Jordi Gol i Gurina(reference number: 16/093). The findings of this trial will bedisseminated through research conferences and peer-reviewed journals.

Trial registration number

NCT02900820; pre-results.
Adverse childhood or adult experiences and risk of bilateral oophorectomy: a population-based case–control study
Authors: Gazzuola Rocca Liliana , Smith Carin Y , Grossardt Brandon R , Faubion Stephanie S , Shuster Lynne T , Stewart Elizabeth A , Rocca Walter A
Published: June 2017

Objectives

Bilateral oophorectomy has commonly been performed in conjunction with hysterectomy even in women without a clear ovarian indication; however, oophorectomy may have long-term deleterious consequences. To better understand this surgical practice from the woman’s perspective, we studied the possible association of adverse childhood or adult experiences with the subsequent occurrence of bilateral oophorectomy.

Design

Population-based case–control study.

Setting

Olmsted County, Minnesota (USA).

Participants

From an established population-based cohort study, we sampled 128 women who underwent bilateral oophorectomy before age 46 years for a non-cancerous condition in 1988–2007 (cases) and 128 age-matched controls (±1 year).

Methods

Information about adverse experiences was abstracted from the medical records dating back to age 15 years or earlier archived in the Rochester Epidemiology Project (REP) records-linkage system. Adverse childhood experiences were summarised using the Adverse Childhood Experience (ACE) score.

Results

We observed an association of bilateral oophorectomy performed before age 46 years with verbal or emotional abuse, physical abuse, any abuse, substance abuse in the household, and with an ACE score ≥1 experienced before age 19 years (OR=3.23; 95% CI 1.73 to 6.02; p<0.001). In women who underwent the oophorectomy before age 40 years, we also observed a strong association with physical abuse experienced during adulthood (OR=4.33; 95% CI 1.23 to 15.21; p=0.02). Several of the associations were higher in women who underwent oophorectomy at a younger age (<40 years) and in women without an ovarian indication for the surgery. None of the psychosocial or medical variables explored as potential confounders or intervening variables changed the results noticeably.

Conclusions

Women who suffered adverse childhood experiences or adult abuse are at increased risk of undergoing bilateral oophorectomy before menopause. We suggest that the association may be explained by a series of biological, emotional, and psychodynamic mechanisms.
Utilising advance care planning videos to empower perioperative cancer patients and families: a study protocol of a randomised controlled trial
Authors: Aslakson Rebecca A , Isenberg Sarina R , Crossnohere Norah L , Conca-Cheng Alison M , Yang Ting , Weiss Matthew , Volandes Angelo E , Bridges John F P , Roter Debra L
Published: June 2017

Introduction

Despite positive health outcomes associated with advance care planning (ACP), little research has investigated the impact of ACP in surgical populations. Our goal is to evaluate how an ACP intervention video impacts the patient centredness and ACP of the patient-surgeon conversation during the presurgical consent visit. We hypothesise that patients who view the intervention will engage in a more patient-centred communication with their surgeons compared with patients who view a control video.

Methods and analysis

Randomised controlled superiority trial of an ACP video with two study arms (intervention ACP video and control video) and four visits (baseline, presurgical consent, postoperative 1 week and postoperative 1 month). Surgeons, patients, principal investigator and analysts are blinded to the randomisation assignment.

Setting

Single, academic, inner city and tertiary care hospital. Data collection began July 16, 2015 and continues to March 2017.

Participants

Patients recruited from nine surgical oncology clinics who are undergoing major cancer surgery.

Interventions

In the intervention arm, patients view a patient preparedness video developed through extensive engagement with patients, surgeons and other stakeholders. Patients randomised to the control arm viewed an informational video about the hospital surgical programme.

Main outcomes and measures

Primary Outcome: Patient centredness and ACP of patient-surgeon conversations during the presurgical consent visit as measured through the Roter Interaction Analysis System. Secondary outcomes: patient Hospital Anxiety and Depression Scale score; patient goals of care; patient, companion and surgeon satisfaction; video helpfulness; medical decision maker designation; and the frequency patients watch the video. Intent-to-treat analysis will be used to assess the impact of video assignment on outcomes. Sensitivity analyses will assess whether there are differential effects contingent on patient or surgeon characteristics.

Ethics and dissemination

This study has been approved by the Johns Hopkins School of Medicine institutional review board and is registered on clinicaltrials.gov (NCT02489799, First received: July 1, 2015).

Trial registration number

clinicaltrials.gov,NCT02489799.
The Handy Approach – Quick Integrated Person Centred Support Preparation
Authors: Risi Liliana , Brown Juliette , Sugarhood Paul , Depala Babalal , Olowosoyo Abi , Tomu Cynthia , Gonzalez Lorena , Munoz-Cobo Maloles , Adekunle Oladimeji , Ogwal Okumu , Evans Eirlys , Shah Amar
Published: June 2017

Cost effective care requires comprehensive person-centred formulation of solutions. The East London NHS Foundation Trust Community Health Services in Newham have piloted models of Integrated Care called ‘Virtual Wards’ which aim to keep people living with multiple long-term conditions, well at home by minimising system complexity. These Virtual Wards comprise Interdisciplinary Teams (IDTs) with a General Practitioner (GP) seconded to provide leadership. Historically assessments have been dominated by biomedical approaches with disability emphasised over personal aspirations and ability. New professional skills are needed to organise information from diverse approaches into a common framework, which can enable agreed goals of care to be delivered collaboratively. From June 2014 to January 2016 we aimed to improve the documentation of person-centred goals of care in 100% of our assessments. Change ideas were tested and team development addressed to improve documentation of aspirations for care for people being referred and if achieved, then to test ideas to improve coproduction of care. Change ideas included Enhanced Clinical Supervision (ECS) by a GP with additional expert skills; Flash Teaching (FT) defined as five-minute weekly discussion on topics generated from the case-mix to develop a shared understanding of Integrated Care; Structured Formulation using a novel, quick, integrated assessment framework called the Handy Approach (HA) with the hand as a memory prompt to bring the personal together with the mental, social and physical domains and finally we tested focusing on ‘Team Primacy’ (mutual regard within the team) to embed behaviour change. 181 cases were tracked and documentation of personal aspirations for care by case showed: ECS 0/21 (0%); FT 5/50 (10%); ECS/FT plus the HA 35/83 (42%); Team Primacy plus ECS/FT/HA 27/27 (100%). By January 2016 prompted by using the Handy Approach in a highly functional team, all members of the IDT consistently documented personal aspirations.
Dealing with possible criminal cases: giving evidence
Authors: Yeates James
Published: June 2017

Vets play an important role in providing evidence to courts on cases of animal cruelty and abuse. In this article, the third in a series on being involved in potential criminal animal welfare cases, James Yeates discusses the important aspects that vets should consider when giving evidence to the court as written or verbal testimony.
Galápagos sperm whales (Physeter macrocephalus): waxing and waning over three decades
Authors: Cantor M. , Eguiguren A. , Merlen G. , Whitehead H.
Published: June 2017

While population sizes and structures naturally fluctuate over time, rapid within-generation changes are usually driven by shifts in habitat quality and (or) abrupt mortality. We evaluate how sperm whales (Physeter macrocephalus L., 1758 = Physeter catodon L., 1758) responded to the dynamic habit off the Galápagos Islands over 30 years, relating it to variation in prey availability and whaling operations in the tropical Pacific. In the 1980s, males and females were commonly sighted foraging and socializing in the northwest of the archipelago. Sightings decreased during the 1990s; by the 2000s, they became very rare: occasional single foraging males were sighted and females abandoned the archipelago. In the 2010s, whales return to the southern waters, in large groups with apparently more breeding males and calves. The waxing and waning of Galápagos sperm whales are likely caused by environmental shifts together with ripple effects of whaling. Their patchy prey are influenced by variation in sea temperature and productivity, which drives movements of whales in and out of the archipelago. Whaling may have aggravated these movements by leaving an attractive surplus of prey in coastal waters depleted of whales. These findings highlight the magnitude of spatiotemporal scales used by sperm whales and the consequent challenges of assessing population dynamics of long-lived, mobile pelagic species.
Retinoic acid as a chemoattractant for cultured embryonic spinal cord neurons of the African Clawed Frog,Xenopus laevis
Authors: Rand C.D. , Spencer G.E. , Carlone R.L.
Published: June 2017

Retinoic acid (RA), an active metabolite of vitamin A, is important for neural development and regeneration and can induce neurite outgrowth. It may also act as a guidance molecule by attracting neurite processes during outgrowth. In the African Clawed Frog (Xenopus laevis (Daudin, 1802)), RA has been shown to play an important role in the development of the anterior–posterior axis. However, whether RA can act as a trophic or tropic molecule on embryonic neurons of this species has not been determined. In this study, we investigated the effects of two retinoid isomers, all-trans retinoic acid (atRA) and 9-cis retinoic acid (9-cisRA), on cultured embryonic spinal cord neurons of X. laevis. Both isomers significantly enhanced neurite outgrowth compared with the vehicle control. In addition, atRA induced growth cone turning, which was blocked with a retinoic acid receptor (RAR) antagonist, selective for the β receptor subtype. Immunostaining also revealed RAR immunoreactivity in the neurites and growth cones of these cells. Interestingly, the 9-cisRA isomer also induced significant growth cone turning and this response was inhibited by a retinoid X receptor (RXR) pan-antagonist. Overall, we have provided evidence for both trophic and chemotropic actions of two naturally occurring retinoid isomers on Xenopus embryonic spinal cord neurons in culture.
Effects of maximum node degree on computer virus spreading in scale-free networks
Authors: Bamaarouf O. , Ould Baba A. , Lamzabi S. , Rachadi A. , Ez-Zahraouy H.
Published: June 2017

The increase of the use of the Internet networks favors the spread of viruses. In this paper, we studied the spread of viruses in the scale-free network with different topologies based on the Susceptible–Infected–External (SIE) model. It is found that the network structure influences the virus spreading. We have shown also that the nodes of high degree are more susceptible to infection than others. Furthermore, we have determined a critical maximum value of node degree [Formula: see text], below which the network is more resistible and the computer virus cannot expand into the whole network. The influence of network size is also studied. We found that the network with low size is more effective to reduce the proportion of infected nodes.
At Light Speed: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior
Authors: Repina Nicole A. , Rosenbloom Alyssa , Mukherjee Abhirup , Schaffer David V. , Kane Ravi S.
Published: June 2017

Cells are bombarded by extrinsic signals that dynamically change in time and space. Such dynamic variations can exert profound effects on behaviors, including cellular signaling, organismal development, stem cell differentiation, normal tissue function, and disease processes such as cancer. Although classical genetic tools are well suited to introduce binary perturbations, new approaches have been necessary to investigate how dynamic signal variation may regulate cell behavior. This fundamental question is increasingly being addressed with optogenetics, a field focused on engineering and harnessing light-sensitive proteins to interface with cellular signaling pathways. Channelrhodopsins initially defined optogenetics; however, through recent use of light-responsive proteins with myriad spectral and functional properties, practical applications of optogenetics currently encompass cell signaling, subcellular localization, and gene regulation. Now, important questions regarding signal integration within branch points of signaling networks, asymmetric cell responses to spatially restricted signals, and effects of signal dosage versus duration can be addressed. This review summarizes emerging technologies and applications within the expanding field of optogenetics.