bluuebunny/crossref_metadata_2025 huggingface dataset:
New trial of convection enhanced drug delivery (CED) in DIPG- applying the SIOPe DIPG survival prediction model for power calculation.
Authors: Szychot Elwira , Collins Peter , Cassidy Hannah , Desai Mohammed , Hyare Harpreet , Shankar Ananth , Gill Steven , van Vuurden Dannis , Veldhuijzen van Zanten Sophie , Walker David
Published: October 2019

Background

In diffuse intrinsic pontine glioma (DIPG) drug resistance is in part due to inadequate penetration of blood-brain barrier (BBB) by systemically administered drugs. Convection-enhanced drug delivery (CED) techniques have been established to bypass BBB. Trial design to measure efficacy requires evidence to justify power calculation.

Aims

To apply SIOPe DIPG registry survival prediction tool to pilot cohort of children with DIPG treated with CED of carboplatin and sodium valproate.

Methods

Case note and imaging review of 9 children with typical DIPG on imaging who were treated on compassionate basis with CED intra-tumoural infusions of carboplatin (0.12 mg/ml) and sodium valproate (14.4 mg/ml), after radiotherapy (n=9) and chemotherapy (n=4). Each had Renishaw device placed with 4 micro-catheters located within tumour mass. Up to 8 treatment cycles of CED infusions delivered through 2 pairs of catheters on 2 days to encompass pontine tumour volume. Survival prediction was performed using clinical criteria: age, sex, duration of symptoms, prior chemotherapy; and radiological criteria: absence of distant metastases; disease involving more than 50% of, and confined to, pons, ring enhancement at diagnosis.

Results

Cases were categorized as intermediate or high-risk using SIOPe risk scoring with predicted median overall survival (OS) of 9.7, and 7.0 months, respectively. Four patients, categorized as high-risk, had median overall survival (OS) of 14.2 months. Five children, categorized as standard-risk, had median OS of 16.0 months.

Conclusions

Results justify a phase 2 trial of CED carboplatin and sodium valproate powered to detect at least 4-month prolongation of survival.
Using surgical and oncology workload to plan brain tumour trial recruitment in England
Authors: Le Calvez Kerlann , Treasure Peter , Williams Matt
Published: October 2019

Introduction

Access to clinical trials is a common request for patients with brain tumours. However, opening clinical trials requires additional work per centre opened. We have previously shown that surgical and oncology workload varies between centres, and fluctuates over time. There is a trade-off between offering access to clinical trials and increasing costs associated with opening trials in centres that treat few patients.

Methods

We used two separate datasets from England covering 3 years – one for neurosurgical workload and one for radiotherapy. We only included adult patients and calculated cumulative proportions of the malignant primary brain tumour population (C71) by number of centres. We investigated stability by checking how many patients would have to be added/ removed from a centre to change their rank.

Results

There were 7061 surgical and 5060 radiotherapy patients. To capture 25% of patients, we would need to open trials in 4 surgical/5 radiotherapy centres; for 50%, 9 surgical/ 13 radiotherapy centres; for 75%, 16 surgical/ 24 radiotherapy centres. Centre rank was fluid: adding 16 surgical/9 radiotherapy patients would change the rank of a centre.

Discussion

These are the first data to allow for rational planning of trials in brain tumour patients. We have shown that we can reach 75% of the brain tumour population by opening trials in ~50% of surgical and radiotherapy centres. Centre rank alters over year, so we should be cautious about being too prescriptive. Nonetheless, these data should allow some rational planning of trial centre inclusion.
Early effects of surgery and radiotherapy on activity levels in patients with brain tumours: preliminary data from the BrainWear trial
Authors: Dadhania Seem , Wei Wang James , Yu Boyu , Saleem Waqar , Blake Catherine , Shahabi Lillie , Williams Matthew
Published: October 2019

Background

BrainWear is a phase II observational clinical trial which collects data on patient activity levels, fatigue, Quality of Life (QoL) and imaging in patients with brain tumours

Methods

Newly diagnosed patients were offered wrist worn accelerometers (Axivity AX3) to be worn continuously throughout their treatment (surgery, chemoradiotherapy or radiotherapy) to monitor physical activity. We collected standardised measures of QoL, fatigue, MRI imaging data and disease progression. Here, we report early results on activity data 5 days before and after treatment.

Results

Of 23 patients recruited, we report complete pre and post treatment data in 4 patients (2 HGG, 2 metastatic) who underwent craniotomy (2), fractionated radiotherapy (1) and SRS (1). Both craniotomy patients experienced an immediate 60 – 70% reduction in activity, and were successfully discharged at day 2 post-op even though their activity was still significantly reduced. Both patients recovered another 10% in their activity levels following discharge. Radiotherapy patients experienced no early change within 5 days of starting treatment.

Conclusion

As expected craniotomy results in much larger changes in activity levels than SRS and radical radiotherapy. Activity levels recover post craniotomy, but this takes > 5 days.

Using wearable activity monitors in brain tumour patients is feasible, although there are multiple practical problems. Interpreting such data will require consideration of inpatient vs. outpatient settings.
Patient Reported Experience Measures in navigated Transcranial Magnetic Stimulation
Authors: Patel Sabina , Lavrador José , Ghimire Prajwal , Gullan Richard , Ashkan Keyoumars , Bhangoo Ranjeev , Vergani Francesco
Published: October 2019

Introduction

Navigated Transcranial Magnetic Stimulation (nTMS) is a non-invasive adjunct used in surgical planning for lesions in eloquent brain. However, its patient tolerability and effect on their overall healthcare experience is still unknown. To our knowledge, there is no other literature available evaluating patient experience with nTMS.

Methods

A single-institution prospective cohort study carried out between February 2018 and December 2018 at King’s College Hospital. All patients were supplied with a PREMs-TMS questionnaire to evaluate the different domains of the nTMS experience.

Results

Feedback was obtained from 50 patients. 26% of patients underwent motor mapping (MM), whilst 74% underwent both motor and language mapping (MLM). The former group reported a better overall experience (p=0.020). The mean exam duration was 103.3±5.1 min (MM 85.8±6.1 min; MLM 106.9±5.9 min). The whole experience of nTMS received positive feedback (94%), particularly with confidence in the staff (95%). Unsurprisingly, the exam domain received a poorer rating (70% as good) with significant anxiety and pain reported in 26% and 24% of patients respectively. None of the studied variables influenced the way patients rated the overall experience of nTMS (p>0.05).

Conclusions

nTMS is a non-invasive investigative tool, which allows patients to better understand their condition and symptoms related to their lesion. Serial assessment and feedback using a PREM tool, can only improve and enhance this experience. Departmental collaboration may be useful in comparing patient experience with nTMS in different centres.
Improving multidisciplinary communication during awake craniotomy: First use of a novel robotic exoscope
Authors: Anzak Anam , Alamri Alex , Doke Thomas , McKenna Grainne , Elsmore Andrew , Paraskevopoulos Dimitri , McKintosh Edward
Published: October 2019

Background

Awake craniotomies require exceptional intra-operative communication between the multidisciplinary team. This is difficult with traditional operating microscopes, where the operative field cannot be visualised by all parties. The Synaptive Modus V is a hands-free, robotic, extracorporeal telescope (exoscope), allowing images to be viewed on multiple large monitors. The Royal London Hospital is the first United Kingdom installation of this device and the first unit in Europe to apply it to awake craniotomies for low-grade glioma.

Methods

Two consecutive patients with low grade glioma underwent awake craniotomy using the Modus V. Qualitative feedback (semi-structured interview) was received from the MDT including surgeons, occupational/ speech and language/ physio-therapists, neurophysiologists, anaesthetists and scrub team. Optimal device positioning is described.

Results

Both female patients (38 and 52 years old) underwent surgery between December 2018 and February 2019. Lesions were located in right perisylvian and posterior inferior frontal gyrus locations respectively.

Surgical resection was satisfactory. Patient 1 developed a wrist-drop intra-operatively. Patient 2 had transient mild word finding difficulties. Surgeons reported easier surgical flow with hands-free positioning, larger working area and improved ergonomics. Adapting to non-stereoscopic vision increased operating times. Multi-disciplinary team members reported an better communication with the operating surgeon during patient assessment and a more involved educational experience.

Conclusion

Hands-free exoscopes may provide improved surgical flow and efficiency for awake craniotomy whilst simultaneously improving multidisciplinary communication and education. There is an, as yet, unidentified learning curve for its use that requires learning curve data generation.
Brain mapping for lesions in primary motor cortex: integrated surgical approach
Authors: Lavrador José , Ghimire Prajwal , Brogna Christian , Furlanetti Luciano , Patel Sabina , Gullan Richard , Ashkan Keyoumars , Bhangoo Ranjeev , Vergani Francesco
Published: October 2019

Background

Lesions within the corticospinal tract (CST) represent significant surgical challenge with a delicate functional trade-off that should be integrated in the overall patient-centred treatment plan.

Methods

Patients with lesions within the CST with preoperative cortical and subcortical mapping (nTMS and tractography), intraoperative mapping and intraoperative provisional histological information (smear +- 5-ALA) were included. This independently acquired information was integrated in a decision-making process model to determine the intraoperative extent of resection.

Results

10 patients (6 patients with metastatic precentral tumour; 1 patient with Grade III and 2 patients with grade IV gliomas; 1 patient with precentral vascular malformation) were included in the study. Majority of the patient had pre-operative motor deficit (60%). 50% patients underwent gross total resection and 40% patients underwent near total resection of the lesions. In only one patient, no surgical resection was possible after both pre-operative and intraoperative mapping. 70% of patients remained stable postoperatively and 20% improved from previous motor weakness.

Conclusion

The independently acquired anatomical (anatomical MRI) and functional (nTMS and tractography) in patients with CST lesions provide a more accurate guide for resection. The inclusion of the histological information (smear +- 5-ALA) further allows the surgical team to balance the potential functional risks within the global treatment plan. Therefore, the patient is kept at the centre of the informed decision making process.
Grade III meningioma: 10 year single centre case series
Authors: Mcgrath Hari , Lavrador Jose , Christodoulides Ioannis , Ghimire Prajwal , Gullan Richard , Bhangoo Ranjeev , Ashkan Keyoumars , Vergani Francesco
Published: October 2019

Rationale

WHO Grade 3 meningiomas are a rare, malignant subtype of meningioma. Few controlled case series detailing its treatment and follow-up are to be found in the literature.

Methods

Retrospective cohort study of patients treated in a single neuro-oncology centre in the period between September 2008 and March 2019 with an initial diagnosis of WHO Grade 3 meningioma. Demographic and clinical data has been collected from the available medical records.

Results

9 patients were included in this series: 2 had convexity, 2 sphenoid wing, 2 parafalcine, 1 parasagittal with a further 3 multiple locations and 1 patient with parietal convexity meningioma. 3 tumours displayed rhabdoid features, whilst 4 displayed papillary features and a further 2 displayed epithelial structures. All patients underwent surgical intervention: 5 patients had a subtotal resection with 3 having total resection. 3/4 of reported Simpson Grading was grade 2, whilst the remaining 1/4 was grade 1. The extent of resection for 1 patient was uncertain. Post surgically, 6 received adjuvant radiotherapy, 2 had no further treatment and 1 received gamma knife therapy. No patient received chemotherapy. 5 patients saw no tumour recurrence at follow up appointments (mean 50 months). Within 2 years of their respective surgical interventions, 4 patients died due to tumour recurrence and associated complications (3 patients).

Conclusion

To establish a uniform approach to treatment of patients with WHO Grade 3 meningiomas is challenging. Management involves a patient-centred approach based on multidisciplinary meeting decisions. Multicentre registries may allow further conclusions.
Transformation of grade II to grade III rhabdoid-papillary meningioma: Is SRS the culprit?
Authors: Christodoulides Ioannis , Pedro Lavrador Jose , Vergani Francesco , Bhangoo Ranjeev , Gullan Richard , Ashkan Keyoumars
Published: October 2019

Objectives

Meningiomas demonstrate specific genetic and epigenetic mutations, whose effect on recurrence and progression is still of limited understanding. Single-fraction stereotactic radiosurgery (SRS) is an established alternative treatment to surgical resection, proven to achieve excellent local disease control with minimal side effects. However, its effects on tumorigenesis and malignant transformation are still uncertain. The published estimated risk ranges from 0.04%-2.6% at 15 years.

Design

Case report

Subjects

Female patient referred to our neurosurgical service

Methods

Retrospective analysis of patient’s notes, histopathology reports, clinic letters, MDT decisions and imaging studies

Results

This report describes a case of a grade II parafalcine meningioma, that was initially resected with a Simpson 2 clearance, and upon recurrence, was managed with a single dose of SRS. More than 7 years later, the meningioma recurred, and due to its increasing size on follow-up imaging, it was re-resected. Histopathology revealed a grade III rhabdoid-papillary lesion, with local brain invasion.

Conclusions

To our knowledge, this was the first report to describe malignant transformation of a grade II to a grade III meningioma following SRS therapy to date. Therefore, considering the recent trend towards SRS-treatment for meningiomas, the treating team should always consider its potential effects on tumorigenesis.
Nondetectable or minimal detectable residue levels of N-(n-butyl) thiophosphoric triamide in bovine tissues and milk from a 28-d NBPT dosing study
Authors: van de Ligt Jennifer , Borghoff Susan J , Yoon Miyoung , Ferguson Lin J , DeMaio William , McClanahan Robert H
Published: October 2019

N-(n-butyl) thiophosphoric triamide (NBPT) (Figure 1) is an active ingredient in nitrogen stabilizer (urease inhibitor), which temporarily inhibits the action of the urease enzyme to improve the efficiency of urea-containing fertilizers. Given the potential for NBPT residues to be present in milk and tissues of dairy cattle, due diligence is needed to demonstrate the safety of NBPT in urea-based fertilizers used on forages and crops intended for consumption by Holstein dairy cows. This study used controlled dosing of NBPT in capsule form to dairy cattle for 28 d, followed by a 14-d depuration phase to assess the potential for residues to exist in milk and tissues of dairy cattle at exaggerated use levels. Fourteen lactating cows were selected for the dosing and depuration phases of the study, based on health, body weight (BW), and milk production. There were four treatment groups: 0 mg NBPT/kg BW (Control) (n = 2 cows), 1 mg NBPT/kg BW (1×) (n = 3 cows), 3 mg NBPT/kg BW (3×) (n = 3 cows), and 10 mg NBPT/kg/BW (10×) (n = 6 cows); levels were based on maximum tolerable amount of urea that a cow can ingest on a daily basis (1×) and the maximum concentration of NBPT commercially used when treating urea (0.1 wt% NBPT in urea). At the end of the 28-d dosing phase, cows were randomly selected for the 14-d depuration phase of the study (one control and three 10× cows). The results showed no NBPT residue is detectable at all dose levels, except that a residue level was above the lower limit of quantitation in a single milk and subcutaneous fat sample in the highest (10×) treatment group, which represents the level of NBPT that would be theoretically present in 10× the lethal dosing of daily consumable urea to a cow. Overall, the study demonstrated that it is unlikely for NBPT residues to be present in cattle milk or edible tissues or to cause negative effects on animal health under good agricultural practice.
Treerecs: an integrated phylogenetic tool, from sequences to reconciliations
Authors: Comte Nicolas , Morel Benoit , Hasic Damir , Guéguen Laurent , Boussau Bastien , Daubin Vincent , Penel Simon , Scornavacca Celine , Gouy Manolo , Stamatakis Alexandros , Tannier Eric , Parsons David P.
Published: October 2019

Motivation

Gene and species tree reconciliation methods are used to interpret gene trees, root them and correct uncertainties that are due to scarcity of signal in multiple sequence alignments. So far, reconciliation tools have not been integrated in standard phylogenetic software and they either lack performance on certain functions, or usability for biologists.

Results

We present Treerecs, a phylogenetic software based on duplication-loss reconciliation. Treerecs is simple to install and to use. It is fast and versatile, has a graphic output, and can be used along with methods for phylogenetic inference on multiple alignments like PLL and Seaview.

Availability

Treerecs is open-source. Its source code (C++, AGPLv3) and manuals are available from https://project.inria.fr/treerecs/

Contact

eric.tannier@inria.fr or david.parsons@inria.fr
Overlap in synaptic neurological condition susceptibility pathways and the neural pannexin 1 interactome revealed by bioinformatics analyses
Authors: Frederiksen Simona D , Wicki-Stordeur Leigh E , Swayne Leigh Anne
Published: October 2019

Many neurological conditions exhibit synaptic impairments, suggesting mechanistic convergence. Additionally, the pannexin 1 (PANX1) channel and signalling scaffold is linked to several of these neurological conditions and is an emerging regulator of synaptic development and plasticity; however, its synaptic pathogenic contributions are relatively unexplored. To this end, we explored connections between synaptic neurodevelopmental disorder and neurodegenerative disease susceptibility genes discovered by genome-wide association studies (GWASs), and the neural PANX1 interactome (483 PANX1-interacting proteins identified from mouse Neuro2a cells). To identify shared susceptibility genes, we compared synaptic suggestive GWAS candidate genes amongst autism spectrum disorders, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Next, to further probe PANX1 signalling pathways at the synapse, we used bioinformatics tools to identify PANX1 interactome signalling pathways and protein-protein interaction clusters. To shed light on synaptic disease mechanisms potentially linking PANX1 and these four neurological conditions, we performed additional cross-analyses between gene ontologies enriched for the PANX1 synaptic and disease-susceptibility gene sets. Finally, to explore the regional specificity of synaptic PANX1-neurological conditions connections, we identified brain region-specific elevations of synaptic PANX1 interactome and GWAS candidate gene set transcripts. Our results confirm considerable overlap in risk genes for autism spectrum disorders and schizophrenia and identify potential commonalities in genetic susceptibility for neurodevelopmental disorders and neurodegenerative diseases. Our findings also pinpointed novel putative PANX1 links to synaptic disease-associated pathways, such as regulation of vesicular trafficking and proteostasis, warranting further validation.
High and stable ATP levels prevent aberrant intracellular protein aggregation
Authors: Takaine Masak , Imamura Hiromi , Yoshida Satoshi
Published: October 2019

ATP at millimolar levels has recently been implicated in the solubilization of cellular proteins. However, the significance of this high ATP level under physiological conditions and the mechanisms that maintain ATP remain unclear. We herein demonstrated that AMP-activated protein kinase (AMPK) and adenylate kinase (ADK) cooperated to maintain cellular ATP levels regardless of glucose levels. Single cell imaging of ATP-reduced yeast mutants revealed that ATP levels in these mutants repeatedly underwent stochastic and transient depletion, which induced the cytotoxic aggregation of endogenous proteins and pathogenic proteins, such as huntingtin and α-synuclein. Moreover, pharmacological elevations in ATP levels in an ATP-reduced mutant prevented the accumulation of α-synuclein aggregates and its cytotoxicity. The removal of cytotoxic aggregates depended on proteasomes, and proteasomal activity cooperated with AMPK or ADK to resist proteotoxic stresses. The present study is the first to demonstrate that cellular ATP homeostasis ensures proteostasis and revealed that suppressing the high volatility of cellular ATP levels prevented cytotoxic protein aggregation, implying that AMPK and ADK are important factors that prevent proteinopathies, such as neurodegenerative diseases.
Lysosomal degradation ensures accurate chromosomal segregation to prevent genomic instability
Authors: Almacellas Eugènia , Day Charles , Ambrosio Santiago , Tauler Albert , Mauvezin Caroline
Published: October 2019

Lysosomes, as primary degradative organelles, are the end-point of different converging pathways including macroautophagy. To date, lysosome function has mainly focused on interphase cells, while their role during mitosis remains controversial. Mitosis dictates the faithful transmission of genetic material among generations, and perturbations of mitotic division lead to chromosomal instability, a hallmark of cancer. Heretofore, correct mitotic progression relies on the orchestrated degradation of mitotic factors, which was mainly attributed to ubiquitin-triggered proteasome-dependent degradation. Here, we show that mitotic transition does not only rely on proteasome-dependent degradation, as impairment of lysosomes increases mitotic timing and leads to mitotic errors, thus promoting chromosomal instability. Furthermore, we identified several putative lysosomal targets in mitotic cells. Among them, WAPL, a cohesin regulatory protein, emerged as a novel p62-interacting protein for targeted lysosomal degradation. Finally, we characterized an atypical nuclear phenotype, the toroidal nucleus, as a novel biomarker for genotoxic screenings. Our results establish lysosome-dependent degradation as an essential event to prevent genomic instability.
Rutin, a Natural Inhibitor of IGPD Protein, Inhibits the Biofilm Formation inStaphylococcus xylosusATCC700404
Authors: Bello-Onaghise God’spower , Xiaoxu Xing , Yonghui Zhou , Qianwei Qu , Wenqiang Cui , Yang Tang , Xingru Chen , Jinpeng Wang , Li Yan-Hua
Published: October 2019

The biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Thus, in order to solve the problem of resistant bacteria, it is very important to find new drugs that can inhibit the formation of biofilms. In recent years, researchers have shifted their attention to natural products. As a flavonoid, rutin has been reported to have a variety of biological activities, interestingly, in this study, the inhibitory effect of rutin on the biofilm ofStaphylococcus xylosuswas investigated. We confirmed that rutin could effectively inhibit the biofilm formation ofS. xylosus, then, for the sake of discussion on how it interferes with the biofilm formation, the interaction between rutin and imidazolyl phosphate dehydratase (IGPD) which has been identified as the key enzyme that plays a vital role in the process of biofilm formation was analyzed by molecular docking, the results showed that rutin had a strong affinity with IGPD, it occupied the hydrophobic cavity of the active center forming four hydrogen bonds and many other interactions. In addition, we proved that rutin was able to combine with IGPD using SPR technique. Therefore, we determined the enzyme activity and histidine content of IGPD, the result indicated that rutin could simultaneously inhibit the activity of IGPD and abrogate the synthesis of histidine. Interestingly, thehisBgene encoding for IGPD and IGPD inS. xylosuswere also significantly inhibited when the bacterial culture was treated with rutin. Taken together, the results have provided evidence that rutin is a natural drug that has the ability to interfere with the formation of biofilm inS. xylosus. It is therefore a potential enzyme inhibitor of IGPD.

Author’s Summary

Staphylococcus xylosushas been isolated from a variety of infections, and the biofilm formed byS. xylosuscan help the bacteria evade the immune system of the host and cause chronic infections. Here, we dealt with this menace by establishing a highly effective drug with the ability to interfere with the process involved in the formation of biofilm inS. xylosus. IGPD has been reported to be directly involved in the formation of biofilm inStaphylococcus xylosusand it is known to be present in a variety of microorganisms. Based on this study, we developed a drug therapy targeting IGPD and at the same time interfere with the formation of biofilm inS. xylosus
The Effect of Foreign Demand on Residential Property Prices: Evidence from Australia
Authors: Wokker Chris , Swieringa John
Published: October 2019

This study estimates the impact of foreign demand for Australian residential real estate on property prices. Using postcode‐level administrative data and fixed‐effects regression techniques we find a positive relationship between foreign investment approvals and price growth. Our analysis suggests that, on average, foreign investment contributed between $80 and $122 to quarterly price growth in Sydney and Melbourne between July 2010 and March 2015. This is a small proportion of the increase in property prices over the period.
Progressive Politics in a Changing World: Challenging the Fallacies of Blue Labour
Authors: Bloomfield Jon
Published: October 2019

In Britain and across Europe, the social alliances that sustained progressive politics for a century are disintegrating. The financial crisis of 2007–8 showed that Labour and its ‘third way’ European followers had got the economics of modern capitalism wrong. With the mainstream left compromised, it has been the nationalist right that has benefitted, re‐defining politics around issues of nation, culture and identity. What is surprising is the number of influential voices across the centre and left of politics who have accepted much of this far‐right analysis and adopted its language and terminology. These trends, especially post‐Brexit, have crystallised in the UK around the label of ‘Blue Labour’. This article examines the fallacies and flaws of the Blue Labour tendency in four key areas—class, economy, family and race—and suggests alternative ways forward, which seek to forge rather than disrupt alliances between the working class and new social movements.
Volume of ropivacaine 0.2% and sciatic nerve block duration: A randomized, blinded trial in healthy volunteers
Authors: Christiansen Claus B. , Madsen Mikkel H. , Rothe Christian , Andreasen Asger M. , Lundstrøm Lars H. , Lange Kai H. W.
Published: October 2019

Background

Sciatic nerve blocks are used for many orthopaedic procedures on the knee, lower leg, foot and ankle. However, as nerve block durations vary considerably, the timing of supplemental analgesia is challenging. Therefore, knowledge on the effect of local anaesthetic (LA) dose on block duration is important to outweigh the benefits of increasing LA dose against the risk of LA systemic toxicity. In this randomized, double‐blind trial, we aimed to explore the relationship between the volume of ropivacaine 0.2% and sciatic nerve block duration. We hypothesized that increasing LA volume would prolong block duration.

Methods

We randomized 60 healthy volunteers to receive one of five volumes of ropivacaine 0.2%: 5, 10, 15, 20, or 30 mL. We used an ultrasound‐guided, catheter‐based technique targeting the sciatic nerve in the infragluteal region. The primary outcome was sensory block duration defined as the time of insensitivity to a cold stimulus. Intergroup differences were tested using one‐way ANOVA.

Results

Mean (SD) sensory block durations for the tibial nerve (TN) with increasing volume were: 9.3 hours (1.7), 10.4 hours (1.6), 9.7 hours (2.9), 10.7 hours (2.8) and 9.9 hours (2.6). Mean (SD) sensory block durations for the common peroneal nerve (CPN) were: 10.6 hours (2.7), 11.9 hours (1.5), 11.0 hours (3.3), 13.2 hours (3.7), and 13.5 hours (6.1). There were no intergroup differences (P = .67 [TN]; P = .25 [CPN]).

Conclusion

We found no effect of increasing the volume of ropivacaine 0.2% from 5 to 30 mL on sensory sciatic nerve block duration.
Exercise‐induced attenuation of treatment side‐effects in patients with newly diagnosed prostate cancer beginning androgen‐deprivation therapy: a randomised controlled trial
Authors: Ndjavera Wilphard , Orange Samuel T. , O'Doherty Alasdair F. , Leicht Anthony S. , Rochester Mark , Mills Robert , Saxton John M.
Published: October 2019

Objectives

(i) To assess whether exercise training attenuates the adverse effects of treatment in patients with newly diagnosed prostate cancer beginning androgen‐deprivation therapy (ADT), and (ii) to examine whether exercise‐induced improvements are sustained after the withdrawal of supervised exercise.

Patients and Methods

In all, 50 patients with prostate cancer scheduled for ADT were randomised to an exercise group (n = 24) or a control group (n = 26). The exercise group completed 3 months of supervised aerobic and resistance exercise training (twice a week for 60 min), followed by 3 months of self‐directed exercise. Outcomes were assessed at baseline, 3‐ and 6‐months. The primary outcome was difference in fat mass at 3‐months. Secondary outcomes included: fat‐free mass, cardiopulmonary exercise testing variables, QRISK®2 (ClinRisk Ltd, Leeds, UK) score, anthropometry, blood‐borne biomarkers, fatigue, and quality of life (QoL).

Results

At 3‐months, exercise training prevented adverse changes in peak O2 uptake (1.9 mL/kg/min, P = 0.038), ventilatory threshold (1.7 mL/kg/min, P = 0.013), O2 uptake efficiency slope (0.21, P = 0.005), and fatigue (between‐group difference in Functional Assessment of Chronic Illness Therapy‐Fatigue score of 4.5 points, P = 0.024) compared with controls. After the supervised exercise was withdrawn, the differences in cardiopulmonary fitness and fatigue were not sustained, but the exercise group showed significantly better QoL (Functional Assessment of Cancer Therapy‐Prostate difference of 8.5 points, P = 0.034) and a reduced QRISK2 score (−2.9%, P = 0.041) compared to controls.

Conclusion

A short‐term programme of supervised exercise in patients with prostate cancer beginning ADT results in sustained improvements in QoL and cardiovascular events risk profile.
Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected first-degree relatives
Authors: Svärd A , Roos Ljungberg K , Brink M , Martinsson K , Sjöwall C , Rantapää Dahlqvist S , Kastbom A
Published: October 2019

The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.
Datafication, value and power in developing countries: Big data in two Indian public service organizations
Authors: Heeks Richard , Rakesh Vanya , Sengupta Ritam , Chattapadhyay Sumandro , Foster Christopher
Published: October 2019

Motivation

Datafication—the growing presence, use and impact of data in social processes—is spreading to all sectors in developing countries. But, to date, there are few analyses of real‐world experiences of datafication in developing country organizations.

Purpose

We address this knowledge gap by analysing evidence of big data in practice in relation to three key issues: implementation, value and power.

Approach and methods

Using interview, observation and documentary sources, we analyse the implementation and impact of big data systems in Indian electricity and transport public sector organizations.

Findings

Big data systems have been much slower to implement than anticipated, and the article exposes the nature and scale of the implementation challenge facing such systems. These are already delivering value for some managers within public service organizations but are, as yet, more operational than strategic and incremental not transformative. Big data systems are facilitating a shift in power from the public sector to the private sector, and from labour and middle management to panopticon‐type control by central managers. Big data intersects with politics especially around the imaginaries of wider stakeholders, changing their view of the financial and political issues that technology can address.

Policy implications

Policy‐makers and practitioners can better understand and plan for big data in development using three frameworks presented in the article: information value chain, decision pyramid, and big data–power model. These expose key issues of implementation, organizational value and power that must be incorporated into big data policy and projects. Benefits of datafication have been largely restricted to senior managers, private contractors and some politicians. To spread these to other stakeholders, including workers and citizens, action must be taken to address both practical and political issues arising in the datafication of development.
A model of emotional stress‐induced binge eating in female mice with no history of food restriction
Authors: Anversa Roberta G. , Campbell Erin J. , Ch'ng Sarah S. , Gogos Andrea , Lawrence Andrew J. , Brown Robyn M.
Published: October 2019

Overeating is a major contributing factor to obesity and related health complications. For women, in particular, negative emotions such as stress strongly influence eating behavior and bingeing episodes. Modeling this type of binge eating in rodents presents challenges: firstly, stress‐induced anorexia is commonly observed in rodents therefore a mild stressor is required in order to observe an orexigenic effect. Second, many studies report using calorie restriction to observe the required behavior; yet this does not necessarily reflect the human condition. Thus, the aim of this study was to develop a model of emotional stress‐induced bingeing independent of caloric restriction. Female and male C57BL/6J mice were divided into ad libitum (n = 20 per sex) and food‐restricted (n = 20 per sex) groups which were both further split into a control group and a group exposed to frustration stress (n = 10 per group). All mice were provided intermittent access to a highly palatable food in 2 cycles. At the end of each cycle the stress group was subjected to a 15‐minute frustration episode where highly palatable food was within the home cage but inaccessible. Both groups were then given free access for 15 minutes. Frustrated female mice from the ad libitum displayed binge‐like behavior compared with controls (P = .0001). Notably, this behavior was absent in males. Ovariectomy had no impact on binge‐like behavior. Collectively, these data validate a novel model of emotional stress‐induced binge eating specific to female mice which does not require caloric restriction and is not driven by ovarian hormones.
Evaluating chronic emotional dysregulation and irritability in relation to ADHD and depression genetic risk in children with ADHD
Authors: Nigg Joel T. , Karalunas Sarah L. , Gustafsson Hanna C. , Bhatt Priya , Ryabinin Peter , Mooney Michael A. , Faraone Stephen V. , Fair Damien A. , Wilmot Beth
Published: October 2019

Background

A central nosological problem concerns the etiological relationship of emotional dysregulation with ADHD. Molecular genetic risk scores provide a novel method for informing this question.

Methods

Participants were 514 community‐recruited children of Northern European descent age 7‐11 defined as ADHD or non‐ADHD by detailed research evaluation. Parents‐rated ADHD on standardized ratings and child temperament on the Temperament in Middle Childhood Questionnaire (TMCQ) and reported on ADHD and comorbid disorders by semi‐structured clinical interview. Categorical and dimensional variables were created for ADHD, emotional dysregulation (implicating disruption of regulation of both anger‐irritability and of positive valence surgency‐sensation seeking), and irritability alone (anger dysregulation). Genome‐wide polygenic risk scores (PRS) were computed for ADHD and depression genetic liability. Structural equation models and computationally derived emotion profiles guided analysis.

Results

The ADHD PRS was associated in variable‐centered analyses with irritability (β = .179, 95% CI = 0.087–0.280; ΔR2 = .034, p < .0002), but also with surgency/sensation seeking (B = .146, 95%CI = 0.052–0.240, ΔR2=.022, p = .002). In person‐centered analysis, the ADHD PRS was elevated in the emotion dysregulation ADHD group versus other ADHD children (OR = 1.44, 95% CI = 1.03–2.20, Nagelkerke ΔR2 = .013, p = .033) but did not differentiate irritable from surgent ADHD profiles. All effects were independent of variation in ADHD severity across traits or groups. The depression PRS was related to oppositional defiant disorder but not to ADHD emotion dysregulation.

Conclusions

Irritability‐anger and surgency‐sensation seeking, as forms of negative and positively valenced dysregulated affect in ADHD populations, both relate principally to ADHD genetic risk and not mood‐related genetic risk.
Fitness consequences of the selfish supergene Segregation Distorter
Authors: Wong Heidi W. S. , Holman Luke
Published: October 2019

Segregation distorters are selfish genetic elements that subvert Mendelian inheritance, often by destroying gametes that do not carry the distorter. Simple theoretical models predict that distorter alleles will either spread to fixation or stabilize at some high intermediate frequency. However, many distorters have substantially lower allele frequencies than predicted by simple models, suggesting that key sources of selection remain to be discovered. Here, we measured the fitness of Drosophila melanogaster adults and juveniles carrying zero, one or two copies of three different variants of the naturally occurring supergene Segregation Distorter (SD), in order to investigate why SD alleles remain relatively rare within populations despite being preferentially inherited. First, we show that the three SD variants differ in the severity and dominance of the fitness costs they impose on individuals carrying them. Second, SD‐carrying parents produced less fit offspring in some crosses, independent of offspring genotype, indicating that SD alleles can have nongenetic, transgenerational costs in addition to their direct costs. Third, we found that SD carriers sometimes produce a biased offspring sex ratio, perhaps due to off‐target effects of SD on the sex chromosomes. Finally, we used a theoretical model to investigate how sex ratio and transgenerational effects alter the population genetics of distorter alleles; accounting for these additional costs helps to explain why real‐world segregation distorter alleles are rarer than predicted.
Association between periodontitis and medication‐related osteonecrosis of the jaw: A systematic review and meta‐analysis
Authors: Lorenzo‐Pouso Alejandro I. , Pérez‐Sayáns Mario , Chamorro‐Petronacci Cintia , Gándara‐Vila Pilar , López‐Jornet Pía , Carballo Javier , García‐García Abel
Published: October 2019

Consensus has yet to be reached about the prevention and treatment of medication‐related osteonecrosis of the jaw (MRONJ), which is a treatment sequela of several antiresorptive therapies and other pharmaceutical interventions. Several epidemiologic studies have identified periodontal disease (PD) as a risk factor for this outcome. Thus, the objective of this systematic review and meta‐analysis was to investigate this association and its magnitude. A systematic search in MEDLINE via PubMed, Scopus and ISI Web of Science, and a meta‐analysis were undertaken. Observational studies that gathered information regarding prefixed definitions for both outcomes were selected, and the relevant information was then extracted, and their risk of bias was evaluated using the Newcastle‐Ottawa Scale. The protocol of the study was registered on PROSPERO (CRD42019125646). The initial search yielded 757 eligible records, of which 12 were deemed adequate for inclusion (5 cohort studies and 7 case‐control studies). On a random‐effects meta‐analysis, the risk of PD in MRONJ‐affected sites compared with at‐risk non‐affected patients was significantly greater, with a risk ratio of 2.75 (95% CI: 1.67‐4.52). Nonetheless, from a pooled analysis of three standardized periodontal measures (ie plaque index, clinical attachment loss and probing depth) no significant results were obtained. MRONJ appears to be associated with an increase in prevalence of PD. The direction of this association, and the factors influencing it must be investigated using further prospective data, and likewise, the possibility for using periodontal therapy as a prevention strategy must be looked into. Periodontal screening needs to be made an indispensable requisite for clinicians in order to establish a correct multidisciplinary approach in MRONJ.
Development and validation of a short version of Chronic Oral Mucosal Disease Questionnaire (COMDQ‐15)
Authors: Wiriyakijja Paswach , Porter Stephen , Fedele Stefano , Hodgson Tim , McMillan Roddy , Shephard Martina , Ni Riordain Richeal
Published: October 2019

Background

The adoption of the Chronic Oral Mucosal Disease Questionnaire (COMDQ) into clinical practice has been low, despite its rigorous development process. A potential limitation of the COMDQ is the high response burden to patients. Therefore, the aim of the present study was to develop and validate a short version of the 26‐item COMDQ.

Methods

The COMDQ data of 520 patients with chronic oral mucosal diseases were randomly divided into two subsamples. Descriptive item analysis and exploratory factor analysis (EFA) were performed using data from the first subsample for item reduction and development of the shortened COMDQ. The resulting short version was then validated using confirmatory factor analysis (CFA) on the other subsample. Internal consistency reliability of the short‐form COMDQ was assessed using Cronbach's alpha. Criterion validity of this new scale was examined against its original version.

Results

Based upon item analysis, 11 items were dropped. EFA results on the remaining 15 items extracted four factors consistent with the original COMDQ, and CFA results displayed acceptable goodness‐of‐fit indices of this factor structure on different sample. The COMDQ‐15 was then created. Cronbach's alpha of four subscale scores ranged from 0.7 to 0.91, indicating good internal consistency reliability of the COMDQ‐15. Correlations between total and subscale scores of the COMDQ‐15 and its parent scale were high, supporting good criterion validity of this shortened scale.

Conclusion

The COMDQ‐15 is a brief, valid and reliable instrument that can give an overview of the patient's quality of life related to their chronic oral mucosal conditions.
A 2‐year randomized blinded controlled trial of a conditionally licensedMoraxella bovoculivaccine to aid in prevention of infectious bovine keratoconjunctivitis in Angus beef calves
Authors: O'Connor Annette , Cooper Vickie , Censi Laura , Meyer Ella , Kneipp Mac , Dewell Grant
Published: October 2019

Background

Infectious bovine keratoconjunctivitis (IBK) in beef cattle has major welfare and production implications. Effective vaccination against IBK would also reduce antibiotic use in beef production.

Objective/Hypothesis

To evaluate the efficacy of a conditionally licensed commercial IBK vaccine containingMoraxella bovoculibacterin. Primary working hypothesis was that animals vaccinated with 2 doses of the commercialM. bovoculivaccine would have a lower risk of disease.

Animals

Spring born calves at a university cow‐calf herd. After excluding animals with ocular lesions, calves eligible for prevention assessment in 2017 and 2018 were 163 (81 vaccinated, 82 unvaccinated) and 207 (105 vaccinated, 102 unvaccinated). One hundred sixty two and two hundred and six calves completed the follow‐up period in 2017 and 2018, respectively.

Methods

A randomized controlled trial. The trial design was a 2‐arm parallel trial with a 1:1 allocation ratio.

Results

In both years, calves receiving the vaccine had more IBK. This effect was small. The pooled risk ratio was 1.30 (95% confidence interval 0.84–2.01). The pooled unadjusted difference in mean weight (kg) at weaning was −0.88 (95% confidence interval—7.2‐5.43).

Conclusions and Clinical Importance

We were unable to document that theM. bovoculibacterin vaccine had a protective effect for the incidence of IBK in our single herd in a 2‐year study.