bluuebunny/crossref_metadata_2025 huggingface dataset:
SLC38A8 mutations result in arrested retinal development with loss of cone photoreceptor specialization
Authors: Kuht Helen J , Han Jinu , Maconachie Gail D E , Park Sung Eun , Lee Seung-Tae , McLean Rebecca , Sheth Viral , Hisaund Michael , Dawar Basu , Sylvius Nicolas , Mahmood Usman , Proudlock Frank A , Gottlob Irene , Lim Hyun Taek , Thomas Mervyn G
Published: August 2020

Foveal hypoplasia, optic nerve decussation defects and anterior segment dysgenesis is an autosomal recessive disorder arising from SLC38A8 mutations. SLC38A8 is a putative glutamine transporter with strong expression within the photoreceptor layer in the retina. Previous studies have been limited due to lack of quantitative data on retinal development and nystagmus characteristics. In this multi-centre study, a custom-targeted next generation sequencing (NGS) gene panel was used to identify SLC38A8 mutations from a cohort of 511 nystagmus patients. We report 16 novel SLC38A8 mutations. The sixth transmembrane domain is most frequently disrupted by missense SLC38A8 mutations. Ninety percent of our cases were initially misdiagnosed as PAX6-related phenotype or ocular albinism prior to NGS. We characterized the retinal development in vivo in patients with SLC38A8 mutations using high-resolution optical coherence tomography. All patients had severe grades of arrested retinal development with lack of a foveal pit and no cone photoreceptor outer segment lengthening. Loss of foveal specialization features such as outer segment lengthening implies reduced foveal cone density, which contributes to reduced visual acuity. Unlike other disorders (such as albinism or PAX6 mutations) which exhibit a spectrum of foveal hypoplasia, SLC38A8 mutations have arrest of retinal development at an earlier stage resulting in a more under-developed retina and severe phenotype.
Genetic risk factors of ME/CFS: a critical review
Authors: Dibble Joshua J , McGrath Simon J , Ponting Chris P
Published: August 2020

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem illness that lacks effective therapy and a biomedical understanding of its causes. Despite a prevalence of ∼0.2–0.4% and its high public health burden, and evidence that it has a heritable component, ME/CFS has not yet benefited from the advances in technology and analytical tools that have improved our understanding of many other complex diseases. Here we critically review existing evidence that genetic factors alter ME/CFS risk before concluding that most ME/CFS candidate gene associations are not replicated by the larger CFS cohort within the UK Biobank. Multiple genome-wide association studies of this cohort also have not yielded consistently significant associations. Ahead of upcoming larger genome-wide association studies, we discuss how these could generate new lines of enquiry into the DNA variants, genes and cell types that are causally involved in ME/CFS disease.
Trend in morbidity and mortality in surgical aortic valve replacement: a retrospective, observational, single-centre study
Authors: Dimagli Arnaldo , Sinha Shubhra , Caputo Massimo , Angelini Gianni D , Benedetto Umberto
Published: August 2020

OBJECTIVES

Continuous improvement in the management of patients undergoing surgical aortic valve replacement (SAVR) may have considerably enhanced surgical outcomes including in-hospital mortality and perioperative complications. We aimed to analyse in-hospital mortality and morbidity trends in patients undergoing SAVR in a single centre to provide insights for future benchmarking for transcatheter aortic valve implantation indications.

METHODS

This was a retrospective study of prospectively collected data from patients undergoing either isolated SAVR or combined with coronary artery bypass grafting (CABG) at the Bristol Heart Institute, UK, from January 2000 to December 2017. Baseline characteristics were extracted and analysed across 3 different eras (2000–2005, 2006–2011 and 2012–2017). Risk-adjusted time trend was obtained from univariate and multivariate logistic regression including all baseline characteristics.

RESULTS

A total of 2719 patients (63.2%) underwent isolated SAVR, and 1581 (36.8%) underwent combined CABG and SAVR during the study period. For patients undergoing SAVR, in-hospital mortality decreased from 2.9% in 2000–2005 to 0.7% in 2012–2017 (risk-adjusted time trend 0.0001). Hospital mortality in patients aged 75–79 and ≥80 years decreased from 5.6% and 5.3% to 0.4% and 2.2%, respectively. Mortality after combined SAVR and CABG did not significantly decrease (from 3.9% in 2000–2005 to 3.5% in 2012–2017; risk-adjusted time trend = 0.62). However, in patients aged ≥80 years, index hospitalization mortality showed a decreasing non-significant trend from 9.8% to 4.8%.

CONCLUSIONS

Our findings support the hypothesis that mortality and morbidity rates following SAVR have significantly improved over the years, including for patients at high risk.
Transitional Justice and Transitional Journalism: Case-Study on Kosovo
Authors: Sweeney James A , Andresen Kenneth , Hoxha Abit
Published: August 2020

This article documents the findings of an empirical project combining socio-legal and media studies, which examined journalists’ perceptions of their role in relation to transitional justice in Kosovo. Based upon the qualitative analysis of 30 semi-structured interviews with professional journalists in Kosovo during the summer of 2018, the article shows that key issues in the study of transitional justice appear in respect of what, building on notions of ‘peace journalism’, can be termed ‘transitional journalism’. Issues include the extent to which ‘transitional journalism’ is, or should be, a distinct ‘field’ at all; as well as debates about the relative priority to give to accountability, reconciliation, historical accounting, or victims’ rights within the practice of ‘transitional journalism’ at any given time. Identifying and engaging with these issues will allow greater agency in, and ownership of, decisions taken about ‘transitional journalism’.
Collective Discussion: Toward Critical Approaches to Intelligence as a Social Phenomenon
Authors: Ben Jaffel Hager , Hoffmann Alvina , Kearns Oliver , Larsson Sebastian
Published: August 2020

This collective discussion proposes a novel understanding of intelligence as a social phenomenon, taking place in a social space that increasingly involves actors and professional fields not immediately seen as part of intelligence. This discussion is a response to the inherent functionalism in Intelligence Studies (IS) that conceives of intelligence as a cycle serving policymakers. Instead, our interventions seek to problematize and break with this notion of the cycle and show what an alternative study of intelligence would look like. In the first part of the discussion, we situate our intervention in the broader fields of IS and International Political Sociology. Espousing a transdisciplinary approach, we build our four interventions as transversal lines cutting through a social space in which agents with differing stakes participate and reframe the meaning and practice of intelligence. Intelligence professionals not only have to reckon with policymakers, but also increasingly with law enforcement agents, representatives from the science and technology sector, judges, lawyers, activists, and Internet users themselves. Each move takes a step further away from the intelligence cycle by introducing new empirical sites, actors, and stakes.
Results from a 1-day workshop on the assessment of quality of life in cancer patients: a joint initiative of the Japan Clinical Oncology Group and the European Organisation for Research and Treatment of Cancer
Authors: Terada Mitsumi , Nakamura Kenichi , Martinelli Francesca , Pe Madeline , Mizusawa Junki , Eba Junko , Fukuda Haruhiko , Kiyota Naomi , Gatellier Laureline , Majima Yoshiyuki , Velikova Galina , Bottomley Andrew
Published: August 2020

This report summarizes the presentations and discussion in the first Japan Clinical Oncology Group-European Organisation for Research and Treatment of Cancer Quality of Life/Patient-Reported Outcome workshop funded by the National Cancer Center Hospital that was held on Saturday, 1 September 2018 in Tokyo, Japan. The infrastructure and understanding regarding the Quality of Life/Patient-Reported Outcome assessment of cancer patients in Japan is still immature, in spite of the increased demand for oncological Patient-Reported Outcome research felt not only by researchers but also by patients or other stakeholders of cancer drug development. The workshop aimed to share each perspective, common issues to be considered and future perspectives regarding the strong alliance between the European Organisation for Research and Treatment of Cancer Quality of Life Group and the Japan Clinical Oncology Group for Quality of Life/Patient-Reported Outcome research as well as explore the possibility of conducting collaborative research. European Organisation for Research and Treatment of Cancer is a leading international cancer clinical trials organization, and its Quality of Life Group is a global leader in the implementation of Quality of Life research in cancer patients. The three invited speakers from the European Organisation for Research and Treatment of Cancer Quality of Life Group presented their perspective, latest methodology and ongoing projects. The three speakers from the Japan Clinical Oncology Group presented their current status, experience and some issues regarding data management or interpretation of the Patient-Reported Outcome data. The two patient advocates also shared their expectations in terms of advances in cancer research based on the Patient-Reported Outcome assessment. As the next steps after this workshop, the Japan Clinical Oncology Group and European Organisation for Research and Treatment of Cancer have decided to cooperate more closely to facilitate Patient-Reported Outcome research in both the groups, and the Japan Clinical Oncology Group has approved the establishment of a new committee for Quality of Life/Patient-Reported Outcome research in Japan.
Incident Command in the Time of COVID-19
Authors: Cook Jim
Published: August 2020

The SARS-CoV-2 virus was initially contained in China but rapidly spread across the globe. The grave threat was not apparent until it was already in our midst. Our organization implemented an Incident Command System (ICS), based on previous experience, to respond to the COVID-19 pandemic in a comprehensive and effective manner. This well-known management and response framework is used by many specialties and organizations in disasters of different complexity and size. Our ICS was able to assemble the appropriate people, assess the situation, and develop and implement plans to deal with the COVID-19 crisis. The effectiveness of the ICS structure and its execution was instrumental in getting in front of the virus and managing regional activities. The ICS is an effective tool to improve safety and mitigate risk when dealing with large-scale disasters and should be implemented and practiced before the need arises.

Our organization implemented a formal Incident Command System (ICS) very early as a response to the COVID-19 pandemic. Although it recently disbanded, we are maintaining its core functionality and communication as we continue to deal with COVID-19 into the future. The author has observed the ICS being used at hospitals through hurricanes, blizzards, and riots but never saw it work as well as it did during the initial weeks of the pandemic. This group deftly navigated through uncharted waters by leveraging the spirit and structure of Incident Command.
The Effect of Sample Site, Illness Duration, and the Presence of Pneumonia on the Detection of SARS-CoV-2 by Real-time Reverse Transcription PCR
Authors: Sutjipto Stephanie , Lee Pei Hua , Tay Jun Yang , Mendis Shehara M , Abdad Mohammad Yazid , Marimuthu Kalisvar , Ng Oon Tek , Cui Lin , Chan Monica , Soon Margaret , Lin Raymond T P , Leo Yee-Sin , De Partha P , Barkham Timothy , Vasoo Shawn ,   National Centre for Infectious Diseases COVID-19 Outbreak Research Team, Ong Sean Wei Xiang , Ang Brenda Sze Peng , Lye David Chien , Lim Poh Lian , Lee Cheng Chuan , Ling Li Min , Lee Lawrence , Young Barnaby Edward , Lee Tau Hong , Wong Chen Seong , Sadarangani Sapna , Lin Ray , Ling Ng Deborah Hee , Sadasiv Mucheli , Chia Po Ying , Choy Chiaw Yee , En Tan Glorijoy Shi , Dimatatac Frederico , Santos Isais Florante , Go Chi Jong , Wen Yeo Tsin , Chan Yu Kit , Rao Pooja , Chia Jonathan W Z , Chen Constance Yuan Yi , Toh Boon Kiat
Published: August 2020

Background

The performance of real-time reverse transcription polymerase chain reaction (rRT-PCR) for SARS-CoV-2 varies with sampling site(s), illness stage, and infection site.

Methods

Unilateral nasopharyngeal, nasal midturbinate, throat swabs, and saliva were simultaneously sampled for SARS-CoV-2 rRT-PCR from suspected or confirmed cases of COVID-19. True positives were defined as patients with at least 1 SARS-CoV-2 detected by rRT-PCR from any site on the evaluation day or at any time point thereafter, until discharge. Diagnostic performance was assessed and extrapolated for site combinations.

Results

We evaluated 105 patients; 73 had active SARS-CoV-2 infection. Overall, nasopharyngeal specimens had the highest clinical sensitivity at 85%, followed by throat, 80%, midturbinate, 62%, and saliva, 38%–52%. Clinical sensitivity for nasopharyngeal, throat, midturbinate, and saliva was 95%, 88%, 72%, and 44%–56%, respectively, if taken ≤7 days from onset of illness, and 70%, 67%, 47%, 28%–44% if >7 days of illness. Comparing patients with upper respiratory tract infection (URTI) vs pneumonia, clinical sensitivity for nasopharyngeal, throat, midturbinate, and saliva was 92% vs 70%, 88% vs 61%, 70% vs 44%, 43%–54% vs 26%–45%, respectively. A combination of nasopharyngeal plus throat or midturbinate plus throat specimen afforded overall clinical sensitivities of 89%–92%; this rose to 96% for persons with URTI and 98% for persons ≤7 days from illness onset.

Conclusions

Nasopharyngeal specimens, followed by throat specimens, offer the highest clinical sensitivity for COVID-19 diagnosis in early illness. Clinical sensitivity improves and is similar when either midturbinate or nasopharyngeal specimens are combined with throat specimens. Upper respiratory specimens perform poorly if taken after the first week of illness or if there is pneumonia.
Taking an Evidence-Based Approach to Evidence-Based Policing Research
Authors: Boulton Laura , Phythian Rebecca , Kirby Stuart , Dawson Ian
Published: August 2020

A growing body of international evidence reflects the increasing recognition of evidence-based policing (EBP) and the co-production of research, yet the extent of which such research is being implemented remains unclear. This study seeks to explore the efficacy of EBP in relation to practical implementation issues and assess the impact research is having on practice, both within and external to a specific Constabulary. Twenty-nine research studies, conducted in association with the Constabulary, were examined using a mixed-method approach. Of the total projects, 52% of projects were found to have generated a change to practice or policy. The key features of research that were associated with impact included: (i) mixed-method data collection, (ii) transferability, and (iii) increased dissemination that engaged practitioner and academic audiences. Practically, these findings suggest that EBP research projects can be designed and disseminated in a way that increases the likelihood of implementing the findings to change practice.
Mechanisms of Network Formation in the Public Sector: A Systematic Review of the Literature
Authors: Siciliano Michael D , Wang Weijie , Medina Alejandra
Published: August 2020

This article provides a systematic review of the network formation literature in the public sector. In particular, we code and categorize the theoretical mechanisms used in empirical network research to motivate collaboration and tie formation. Based on a review of the 107 articles on network formation found in 40 journals of public administration and policy from 1998 to 2019, we identify 15 distinct theoretical categories. For each category, we describe the theory, highlight its use in the literature, and identify limitations and concerns with current applications. Overall, we find that most studies rely on a similar set of general theories of network formation. More importantly, we find that most theoretical mechanisms are not well specified, and empirical tests are often unable to directly assess the specific underlying mechanism. The results of our review highlight the need for our field to embrace experimental designs, develop panel network datasets, and engage in more network-level research.
Neural fatigue due to intensive learning is reversed by a nap but not by quiet waking
Authors: Nelson Aaron B , Ricci Serena , Tatti Elisa , Panday Priya , Girau Elisa , Lin Jing , Thomson Brittany O , Chen Henry , Marshall William , Tononi Giulio , Cirelli Chiara , Ghilardi M Felice
Published: August 2020

Do brain circuits become fatigued due to intensive neural activity or plasticity? Is sleep necessary for recovery? Well-rested subjects trained extensively in a visuo-motor rotation learning task (ROT) or a visuo-motor task without rotation learning (MOT), followed by sleep or quiet wake. High-density electroencephalography showed that ROT training led to broad increases in EEG power over a frontal cluster of electrodes, with peaks in the theta (mean ± SE: 24% ± 6%, p = 0.0013) and beta ranges (10% ± 3%, p = 0.01). These traces persisted in the spontaneous EEG (sEEG) between sessions (theta: 42% ± 8%, p = 0.0001; beta: 35% ± 7%, p = 0.002) and were accompanied by increased errors in a motor test with kinematic characteristics and neural substrates similar to ROT (81.8% ± 0.8% vs. 68.2% ± 2.3%; two-tailed paired t-test: p = 0.00001; Cohen’s d = 1.58), as well as by score increases of subjective task-specific fatigue (4.00 ± 0.39 vs. 5.36 ± 0.39; p = 0.0007; Cohen’s d = 0.60). Intensive practice with MOT did not affect theta sEEG or the motor test. A nap, but not quiet wake, induced a local sEEG decrease of theta power by 33% (SE: 8%, p = 0.02), renormalized test performance (70.9% ± 2.9% vs 79.1% ± 2.7%, p = 0.018, Cohen’s d = 0.85), and improved learning ability in ROT (adaptation rate: 71.2 ± 1.2 vs. 73.4 ± 0.9, p = 0.024; Cohen’s d = 0.60). Thus, sleep is necessary to restore plasticity-induced fatigue and performance.
Assembling the Local Politics of Noncitizenship: Contesting Access to Healthcare in Toronto-Sanctuary City
Authors: Landolt Patricia
Published: August 2020

The article presents a case study of precarious noncitizen healthcare politics based on participant observation and interviews conducted between 2009 and 2012, as well as on documentary evidence collected during this period and up to 2016. It examines how state regulations, social networks, cultural narratives, and discretion come together to assemble the terms of access to healthcare for migrant noncitizens. Analysis shows how local contestation over healthcare policies, procedures and delivery practices contribute to the production of the formal and substantive boundaries between and within citizenship and noncitizenship. The case study identifies how precarious legal status and illegality inform the regulatory incongruencies and discursive fragility of Canada’s liberal welcome for newcomers. It contributes to specifying the conceptual terrain of contemporary battles over the terms of membership for migrant noncitizens in the Global North.
Hate Speech and the Polarization of Japanese National Newspapers
Authors: MERKLEJN Iwona , WIŚLICKI Jan
Published: August 2020

In 2016, the first anti-hate speech law in Japan was introduced against the backdrop of verbal attacks on ethnic Koreans who were targeted with particular force by radical right organizations in the early 21st century. We argue that while the role of social media in the proliferation of hate speech in Japan has received considerable attention, the coverage of hate speech and related issues in mainstream news media has not been sufficiently studied. This article offers an interdisciplinary analysis, grounded in media studies and in linguistics, of the positions of five national newspapers in public discourse about hate speech, discussed as a current issue in Japan from 2016 until mid-2018. We combine agenda-setting theory with discourse analysis of factual reporting in order to evaluate the Japanese media landscape, which, when scrutinized through the lens of the hate speech issue, reveals ideological polarization.
Evaluation of an active live yeast (Levucell Saccharomyces cerevisiae, CNCM l-1077) on receiving and backgrounding period growth performance and efficiency of dietary net energy utilization in low health risk beef steers1
Authors: Smith Zachary K , Karges Kip , Aguilar Angel
Published: August 2020

The objective of this experiment was to evaluate the influence of an active live yeast direct-fed microbial (DFM) product on receiving and backgrounding period growth performance and efficiency of dietary net energy (NE) utilization in low health risk beef steers. Maine-Anjou × Angus steers (n = 199; body weight [BW] = 252 ± 32.1 kg) were received from two sources at the Ruminant Nutrition Center in Brookings, SD, in November 2019 and used in a 77-d feedlot receiving and backgrounding experiment. Steers were provided access to long-stem hay and ad libitum water upon arrival. Steers were weighed, vaccinated for respiratory pathogens (source 2 only): infectious bovine rhinotracheitis, bovine viral diarrhea types 1 and 2, parainfluenza-3 virus, and bovine respiratory syncytial virus (Bovi-Shield Gold 5, Zoetis, Parsippany, NJ) vaccinated for clostridial species (Ultrabac 7/Somubac, Zoetis) and pour-on moxidectin (Cydectin, Bayer, Shawnee Mission, KS). Steers (n = 176 steers; initial unshrunk BW = 235 ± 27.6 kg) were allotted to pens (n = 20 pens; 10 pens per treatment; eight or nine steers per pen). Diets were based upon corn silage, dry-rolled corn, and dried distillers grains; dietary treatments were 1) no DFM (CON) and 2) DFM (Levucell SC, Advantage Titan, CNCM l-1077), fed at 10 g/steer/d providing 8 × 109 CFU of active live yeast to each steer daily (DFM). Initial BW was the average of day −1 and day 1 BW (n = 176 steers; initial BW = 253 ± 27.6 kg). On day 21, steers received a 200-mg progesterone and 20-mg estradiol benzoate implant. Data were analyzed from day 1 to 47 (receiving period), day 48 to 77, and from day 1 to 77 as a randomized complete block design; pen served as the experimental unit for all analyses. On day 47 of the experiment, DFM had greater BW (P = 0.01) by 0.9% and average daily gain (ADG; P = 0.01) by 4.2% and gain-to-feed ratio (G:F) tended (P = 0.13) to be 2.8% greater. Day 77 BW did not differ (P = 0.60), cumulative (days 1–77): ADG (P = 0.47), dry matter intake (P = 0.66), and G:F (P = 0.56) were similar. Yeast inclusion had no appreciable influence on performance-based dietary NE utilization or the ratio of observed/expected dietary NE (P ≥ 0.59). In low health risk steers, DFM improved performance during the feedlot receiving period. However, no improvements for DFM were detected for cumulative performance from day 1 to 77. The confirmation of yeast counts indicated the CFU to be above the expected level at the start of the trial but was found below expected level at the end of the trial. This may explain differences during the initial 47 d compared to cumulative growth performance results.
Impact of the 2017 American Heart Association and American College of Cardiology hypertension guideline in aged individuals
Authors: Chowdhury Enayet Karim , Ernst Michael E. , Nelson Mark , Margolis Karen , Beilin Lawrie J. , Johnston Collin , Woods Robyn , Murray Anne , Wolfe Rory , Storey Elsdon , Shah Raj C. , Lockery Jessica , Tonkin Andrew , Newman Anne , Abhayaratna Walter , Stocks Nigel , Fitzgerald Sharyn , Orchard Suzanne , Trevaks Ruth , Donnan Geoffrey , Grimm R. , McNeil John , Reid Christopher M.
Published: August 2020

Objectives:

The AHA/ACC-2017 hypertension guideline recommends an age-independent target blood pressure (BP) of less than 130/80 mmHg. In an elderly cohort without established cardiovascular disease (CVD) at baseline, we determined the impact of this guideline on the prevalence of hypertension and associated CVD risk.

Methods:

Nineteen thousand, one hundred and fourteen participants aged at least 65 years from the ASPirin in Reducing Events in the Elderly (ASPREE) study were grouped by baseline BP: ‘pre-2017 hypertensive’ (BP ≥140/90 mmHg and/or on antihypertensive drugs); ‘reclassified hypertensive’ (normotensive by pre-2017 guidelines; hypertensive by AHA/ACC-2017 guideline), and ‘normotensive’ (BP <130 and <80 mmHg). For each group, we evaluated CVD risk factors, predicted 10-year CVD risk using the Atherosclerotic Cardiovascular Disease (ASCVD) risk equation, and reported observed CVD event rates during a median 4.7–year follow-up.

Results:

:Overall, 74.4% (14 213/19 114) were ‘pre-2017 hypertensive’; an additional 12.3% (2354/19 114) were ‘reclassified hypertensive’ by the AHA/ACC-2017 guideline. Of those ‘reclassified hypertensive’, the majority (94.5%) met criteria for antihypertensive treatment although 29% had no other traditional CVD risk factors other than age. Further, a relatively lower mean 10-year predicted CVD risk (18% versus 26%, P < 0.001) and lower CVD rates (8.9 versus 12.1/1000 person-years, P = 0.01) were observed in ‘reclassified hypertensive’ compared with ‘pre-2017 hypertensive’. Compared with ‘normotensive’, a hazard ratio (95% confidence interval) for CVD events of 1.60 (1.26–2.02) for ‘pre-2017 hypertensive’ and 1.26 (0.93–1.71) for ‘reclassified hypertensive’ was observed.

Conclusion:

Applying current CVD risk calculators in the elderly ‘reclassified hypertensive’, as a result of shifting the BP threshold lower, increases eligibility for antihypertensive treatment but documented CVD rates remain lower than hypertensive patients defined by pre2017 BP thresholds.
Small-fibre pathology has no impact on somatosensory system function in patients with fibromyalgia
Authors: Fasolino Alessandra , Di Stefano Giulia , Leone Caterina , Galosi Eleonora , Gioia Chiara , Lucchino Bruno , Terracciano Alessandra , Di Franco Manuela , Cruccu Giorgio , Truini Andrea
Published: August 2020

We aimed to investigate whether small-fibre pathology, a common skin biopsy finding in patients with fibromyalgia, implies clinically important abnormalities of somatosensory system function and verify whether it is associated with voltage-gated sodium channel variants. In 57 consecutively enrolled patients with fibromyalgia, we used skin biopsy to distinguish patients with and without small-fibre pathology. In all patients, we assessed somatosensory system function using quantitative sensory testing (QST) and laser-evoked potentials and investigated voltage-gated sodium channel genotyping. We then compared these variables in patients with and without small-fibre pathology. We found that clinical measures, QST, and laser-evoked potential variables did not differ between patients with and without small-fibre pathology. In most patients with small-fibre pathology, QST and laser-evoked potential variables fell within normative ranges commonly used in clinical practice. Of the 57 patients, one patient without small-fibre pathology and 2 patients with small-fibre pathology had rare variants of voltage-gated sodium channels, namely SCN11A, SCN9A, and SCN1A variants. The SCN9A variant, found in a patient with small-fibre pathology, was an already profiled gain-of-function mutation, previously reported in small-fibre neuropathy. Our findings suggest that small-fibre pathology has a negligible impact on somatosensory system function in fibromyalgia. The genetic analysis suggests that patients with rare small-fibre neuropathy due to voltage-gated sodium channel variants may be misdiagnosed as patients with fibromyalgia.
An experimental investigation into the mediating role of pain-related fear in boosting nocebo hyperalgesia
Authors: Thomaidou Mia Athina , Veldhuijzen Dieuwke Swaantje , Meulders Ann , Evers Andrea Walburga Maria
Published: August 2020

Nocebo hyperalgesia refers to increases in perceived pain that putatively result from negative expectations regarding a nocebo stimulus (eg, an inert treatment, compared with no treatment). The precise cognitive-emotional factors contributing to the origins of nocebo effects are poorly understood. We aimed to test the effects of experimentally induced pain-related fear on the acquisition and extinction of nocebo hyperalgesia in healthy participants (N = 72). Acquisition and extinction of nocebo hyperalgesia were compared between a group receiving standard nocebo conditioning (Control group) and 2 groups receiving distinct fear inductions: high intensity of pain stimulations (High-pain group) or a threat manipulation (High-threat group). During nocebo acquisition, the Control and High-threat groups were administered thermal pain stimulations of moderate intensity paired with sham electrical stimulation (nocebo trials), whereas high pain intensity was administered to the High-pain group. During extinction, equivalent pain intensities were administered across all trials. Pain-related fear was measured by eyeblink startle electromyography and self-report. Nocebo hyperalgesia occurred in all groups. Nocebo effects were significantly larger in the High-pain group than those in the Control group. This effect was mediated by self-reported fear, but not by fear-potentiated startle. Groups did not differ in the extinction rate. However, only the High-pain group maintained significant nocebo responses at the end of extinction. Anticipatory pain-related fear induced through a threat manipulation did not amplify nocebo hyperalgesia. These findings suggest that fear of high pain may be a key contributor to the amplification of nocebo hyperalgesia, only when high pain is experienced and not when it is merely anticipated.
GABA and glutamate in pediatric migraine
Authors: Bell Tiffany , Stokoe Mehak , Khaira Akashroop , Webb Megan , Noel Melanie , Amoozegar Farnaz , Harris Ashley D.
Published: August 2020

Migraine is one of the top 5 most prevalent childhood diseases; however, effective treatment strategies for pediatric migraine are limited. For example, standard adult pharmaceutical therapies are less effective in children and can carry undesirable side effects. To develop more effective treatments, improved knowledge of the biology underlying pediatric migraine is necessary. One theory is that migraine results from an imbalance in cortical excitability. Magnetic resonance spectroscopy (MRS) studies show changes in GABA and glutamate levels (the primary inhibitory and excitatory neurotransmitters in the brain, respectively) in multiple brain regions in adults with migraine; however, they have yet to be assessed in children with migraine. Using MRS and GABA-edited MRS, we show that children (7-13 years) with migraine and aura had significantly lower glutamate levels in the visual cortex compared to controls, the opposite to results seen in adults. In addition, we found significant correlations between metabolite levels and migraine characteristics; higher GABA levels were associated with higher migraine burden. We also found that higher glutamate in the thalamus and higher GABA/Glx ratios in the sensorimotor cortex were associated with duration since diagnosis, i.e., having migraines longer. Lower GABA levels in the sensorimotor cortex were associated with being closer to their next migraine attack. Together, this indicates that GABA and glutamate disturbances occur early in migraine pathophysiology and emphasizes that evidence from adults with migraine cannot be immediately translated to pediatric sufferers. This highlights the need for further mechanistic studies of migraine in children, to aid in development of more effective treatments.
Intraocular Pressure Responses to Four Different Isometric Exercises in Men and Women
Authors: Vera Jesús , Redondo Beatriz , Koulieris George-Alex , Torrejon Alejandro , Jiménez Raimundo , Garcia-Ramos Amador
Published: August 2020

SIGNIFICANCE

The performance of resistance exercise has evidenced to induce abrupt intraocular pressure (IOP) changes, which has been linked to the onset and progression of glaucoma. We found that four different isometric resistance exercises lead to an instantaneous and progressive IOP elevation, with these changes being independent of the type of exercise.

PURPOSE

The impact of physical exercise on IOP has demonstrated to be dependent on exercise type and intesity, as well as individuals' characteristics. In this study, we aimed to explore the influence of the load, exercise type, and participant's sex on the IOP behavior during a 2-minute isometric effort.

METHODS

Twenty-eight physically active collegiate students performed 2 minutes of isometric exercise in the military press, biceps curl, leg extension, and calf raise exercises against two different loads (high load and low load). Intraocular pressure was measured by rebound tonometry before, during (semicontinuos assessment [24 measurements]), and after 10 seconds of recovery in each of the eight (four exercises × two loads) conditions.

RESULTS

We found a statistically significant effect of load (P < .001, n
p
2 = 0.906), with greater IOP values when performing the isometric exercises against heavier loads. There was a positive IOP rise during the execution of isometric exercise in the high-load condition, returning to baseline levels after 10 seconds of passive recovery. The exercise type and participant's sex did not reveal statistically significant differences (P = .33 and P = .56, respectively).

CONCLUSIONS

Our data evidenced an instanteneous and progressive IOP rise during the execution of isometric exercise leading to muscular failure, regardless of the exercise type and participant's sex. After exercise, IOP rapidly retuned to baseline levels (within 10 seconds). The inclusion of glaucoma patients in future studies is guarranteed.
Peripapillary Retinal and Choroidal Perfusion in Nonarteritic Ischemic Optic Neuropathy Using Optical Coherence Tomography Angiography
Authors: Dhiman Rebika , Chawla Rohan , Azad Shorya Vardhan , Kumar Pawan , Gupta Vinay , Kumar Atul , Saxena Rohit
Published: August 2020

SIGNIFICANCE

Nonarteritic ischemic optic neuropathy (NAION) has been linked with vascular insufficiency, although the pathophysiology remains elusive. Optical coherence tomography angiography (OCTA) is a promising technology that noninvasively evaluates optic disc perfusion and that may help to characterize peripapillary vascular changes in NAION.

PURPOSE

This study aimed to evaluate peripapillary vascularity in NAION eyes and to compare it with fellow unaffected eyes and healthy control eyes using OCTA.

METHODS

In this cross-sectional study, OCTA of the optic nerve head was obtained in 10 nonacute unilateral NAION and 12 healthy age-matched controls using ZEISS Angioplex. Quantitative analysis of peripapillary retinal and choroidal vascularity of NAION eyes was done using the instrument's inbuilt algorithm and ImageJ software and compared with fellow and control eyes.

RESULTS

Mean total peripapillary superficial retinal vessel and perfusion density as calculated by the instrument was significantly reduced in NAION eyes compared with fellow eyes (13.93 ± 4.27 mm−1/0.36 ± 0.07 for NAION eyes; 17.77 ± 1.26 mm−1/0.43 ± 0.08 for fellow eyes; P = .01/P = .05). Using the ImageJ software technique, the mean superficial retinal perfusion was found to be significantly reduced in NAION eyes (0.17 ± 0.07) compared with fellow eyes (0.25 ± 0.06; P < .01) and control eyes (0.25 ± 0.04; P < .01). At the level of choriocapillaris, it was not significantly affected in NAION eyes (0.37 ± 0.13) versus fellow (0.34 ± 0.14; P = .1) and control eyes (0.31 ± 0.34; P = .83). Analysis with the two techniques yielded differing results: the ImageJ analysis technique found a 32% reduction in superficial retinal perfusion in NAION eyes, whereas the instrument's inbuilt algorithm found a 16% reduction compared with fellow and control eyes (P ≤.01).

CONCLUSIONS

Peripapillary vascularity can be estimated both at the retinal and choroidal levels using ImageJ software to analyze OCTA images. Retinal peripapillary vascularity is compromised in NAION eyes, but vascularity is not significantly affected at the choroidal level.
Novel Dual-Energy Computed Tomography Enterography Iodine Density Maps Provide Unique Depiction of Crohn Disease Activity
Authors: Dane Bari , O'Donnell Thomas , Ream Justin , Chang Shannon , Megibow Alec
Published: August 2020

Objective

To create a map of iodine densities within affected segments of small-bowel Crohn disease (CD) derived from contrast-enhanced dual-energy computed tomography enterography (DECTE) studies.

Methods

Twenty CD patients imaged with intravenous contrast-enhanced DECTE between June 2016 and December 2017 were retrospectively identified. Ten patients without clinical evidence of CD and 8 normal-appearing jejunal segments in CD patients were controls. Using prototype software, 8 manual contours were drawn along the mucosa of affected segments. Relatively normal-appearing bowel was included at the edges. These contours served as a basis for iodine density calculation and 3-dimensional iodine density map rendering. Color-coded iodine densities allowed detection and quantification of the most and least dense portion of each segment and also permitted relative comparison between segments.

Results

The average iodine density per CD involved segment ranged 1.0 to 3.3 mg/mL, which differed significantly from normal ileum (P < 0.0001) and normal-appearing jejunum in patients with CD (P = 0.0009). Standard deviations ranged from 0.8 to 1.7 mg/mL, which differed significantly from normal ileum (P = 0.0039) and normal-appearing jejunum in patients with CD (P = 0.0056). The amplitude of the power spectrum ranged from 0.66 to 3.3 demonstrating patches of iodine rather than uniform distribution. This differed significantly from normal ileum (P = 0.0005) and normal-appearing jejunum in patients with CD (P = 0.0004).

Conclusions

Heterogeneous CD activity and distribution can be displayed as iodine density maps created from DECTE.
Feasibility of Low Volume of High-Concentration Iodinated Contrast Medium With 70 kVp Tube Voltage on High-Pitch Dual-Source Computed Tomography Angiography in Children With Congenital Heart Disease
Authors: Nie Pei , Guo Jian , Yang Zhitao , Li Xiaoli , Yang Guangjie
Published: August 2020

Objective

The objective of this study was to investigate the feasibility of high-concentration iodinated contrast medium (CM) with 70 kVp tube voltage on high-pitch dual-source computed tomography (DSCT) in children with congenital heart disease (CHD).

Methods

Fifty-eight CHD patients underwent high-pitch DSCT in 2 protocols: 70 kVp tube voltage, 1.0 mL/kg CM volume, 370 mg I/mL concentration (group A); 80 kVp tube voltage, 1.5 mL/kg CM volume, 350 mg I/mL concentration (group B). The diagnostic accuracy, image quality, iodine delivery rate, iodine dose, and radiation dose were compared.

Results

There was no significant difference in the diagnostic accuracy (P > 0.05), image quality (P > 0.05) and iodine delivery rate (P > 0.05) between the 2 groups. The iodine dose (P < 0.05) and radiation dose (P < 0.05) in group A were significantly lower than those in group B.

Conclusions

Reduction in iodine dose and radiation exposure can be achieved with 70 kVp high-pitch DSCT by administering a smaller volume of high-concentration CM in children with CHD.
Passively parallel regularized stokeslets
Authors: Gallagher Meurig T. , Smith David J.
Published: August 2020

Stokes flow, discussed by G.G. Stokes in 1851, describes many microscopic biological flow phenomena, including cilia-driven transport and flagellar motility; the need to quantify and understand these flows has motivated decades of mathematical and computational research. Regularized stokeslet methods, which have been used and refined over the past 20 years, offer significant advantages in simplicity of implementation, with a recent modification based on nearest-neighbour interpolation providing significant improvements in efficiency and accuracy. Moreover this method can be implemented with the majority of the computation taking place through built-in linear algebra, entailing that state-of-the-art hardware and software developments in the latter, in particular multicore and GPU computing, can be exploited through minimal modifications (‘passive parallelism’) to existing Matlab computer code. Hence, and with widely available GPU hardware, significant improvements in the efficiency of the regularized stokeslet method can be obtained. The approach is demonstrated through computational experiments on three model biological flows: undulatory propulsion of multipleCaenorhabditis elegans, simulation of progression and transport by multiple sperm in a geometrically confined region, and left–right symmetry breaking particle transport in the ventral node of the mouse embryo. In general an order-of-magnitude improvement in efficiency is observed. This development further widens the complexity of biological flow systems that are accessible without the need for extensive code development or specialist facilities.

This article is part of the theme issue ‘Stokes at 200 (part 2)’.
Fundicoccus ignavus gen. nov., sp. nov., a novel genus of the family Aerococcaceae isolated from bulk tank milk
Authors: Siebert Annemarie , Huptas Christopher , Wenning Mareike , Scherer Siegfried , Doll Etienne V.
Published: August 2020

Three strains of a Gram-stain-positive, catalase-negative, facultative anaerobic, and coccoid species were isolated from German bulk tank milk. Phylogenetic analyses based on the 16S rRNA gene sequences indicated that the three strains (WS4937T, WS4759 and WS5303) constitute an independent phylogenetic lineage within the family

Aerococcaceae

with

Facklamia hominis

CCUG 36813T (93.7–94.1 %) and

Eremococcus coleocola

M1831/95/2T (93.5 %) as most closely related type species. The unclassified strains demonstrated variable growth with 6.5 % (w/v) NaCl and tolerated pH 6.5–9.5. Growth was observed from 12 to 39 °C. Their cell-wall peptidoglycan belongs to the A1α type (l-Lys-direct) consisting of alanine, glutamic acid and lysine. The predominant fatty acids were C16 : 1 ω9c, C16 : 0 and C18 : 1 ω9c and in the polar lipids profile three glycolipids, a phospholipid, phosphatidylglycerol, phosphoglycolipid and diphosphatidylglycerol were found. The G+C content of strain WS4937T was 37.4 mol% with a genome size of ~3.0 Mb. Based on phylogenetic, phylogenomic and biochemical characterizations, the isolates can be demarcated from all other genera of the family

Aerococcaceae

and, therefore, the novel genus Fundicoccus gen. nov. is proposed. The type species of the novel genus is Fundicoccus ignavus gen. nov., sp. nov. WS4937T (=DSM 109652T=LMG 31441T).
Monitoring systems for resistance to plant protection products across the world: Between redundancy and complementarity
Authors:   The Reflection and Research Ring on Pesticide Resistance (R4P) is constituted of, Barrès Benoit , Corio-Costet Marie-France , Debieu Danièle , Délye Christophe , Fillinger Sabine , Gauffre Bertrand , Grosman Jacques , Hannachi Mourad , Jerphanion Pauline de , Le Goff Gaëlle , Plantamp Christophe , Siegwart Myriam , Walker Anne-Sophie , Nistrup-Jørgensen Lise
Published: August 2020

BACKGROUND

Monitoring resistance to Plant Protection Products (PPPs) is crucial for understanding the evolution of resistances in bioagressors, thereby allowing scientists to design sound bioagressor management strategies. Globally, resistance monitoring is implemented by a wide range of actors that fall into three distinct categories: academic, governmental, and private. The purpose of this study was to investigate worldwide diversity in PPP resistance monitoring systems, and to shed light on their different facets.

RESULTS

A large survey involving 162 experts from 48 countries made it possible to identify and analyze 250 resistance monitoring systems. Through an in-depth analysis, the features of the different monitoring systems were identified. The main factor differentiating monitoring systems was essentially the capabilities (funding, manpower, technology, etc.) of the actors involved in each system. In most countries, and especially in those with a high Human Development Index, academic, governmental, and private monitoring systems coexist. Overall, systems focus far more on monitoring established resistances than on the detection of emerging resistances. Governmental and private resistance monitoring systems generally have considerable capacities to generate data, whereas academic resistance monitoring systems are more specialized. Governmental actors federate and enroll a wider variety of stakeholders.

CONCLUSION

The results show functional complementarities between the coexisting actors in countries where they coexist. We suggest PPP resistance monitoring might be enhanced if the different actors focus more on detecting emerging resistances (and associated benefits) and increase collaborative and collective efforts and transparency.
Assessing Confidence in Root Placement on Phylogenies: An Empirical Study Using Non-Reversible Models for Mammals
Authors: Naser-Khdour Suha , Minh Bui Quang , Lanfear Robert
Published: August 2020

Abstract

Using time-reversible Markov models is a very common practice in phylogenetic analysis, because although we expect many of their assumptions to be violated by empirical data, they provide high computational efficiency. However, these models lack the ability to infer the root placement of the estimated phylogeny. In order to compensate for the inability of these models to root the tree, many researchers use external information such as using outgroup taxa or additional assumptions such as molecular-clocks. In this study, we investigate the utility of non-reversible models to root empirical phylogenies and introduce a new bootstrap measure, therootstrap, which provides information on the statistical support for any given root position.

Availability and implementation

rootstrap support is implemented in IQ-TREE 2 and a tutorial is available at the iqtree webpagehttp://www.iqtree.org/doc/Rootstrap. In addition, a python script is available athttps://github.com/suhanaser/Rootstrap. [phylogenetic inference, root estimation, bootstrap, non-reversible models]