bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intergenerational Equity, Ocean Governance, and the United Nations
Authors: Fitzmaurice Malgosia 
Published: October 2018

Abstract
This chapter examines the role of the United Nations (UN) in fulfilling the concept of intergenerational equity as it relates to ocean governance. The concept of intergenerational equity is inexorably linked to the principle of sustainable development. Three basic principles underpin intergenerational equity: conservation of options, conservation of quality, and conservation of access. The chapter first considers the concept of intergenerational equity within the context of sustainable development and environmental protection before discussing international conventions and soft law instruments including the principle of intergenerational equity. It then explains how the UN Convention on the Law of the Sea (UNCLOS) takes into account intergenerational equity and goes on to review national and international case-law concerning intergenerational equity and the rights of future generations. It also analyses constitutional and institutional protection of the rights of future generations and concludes with an assessment of UN approaches addressing the needs of future generations.
The relationship between remission and health-related quality of life in a cohort of SLE patients
Authors: Tsang-A-Sjoe Michel W P , Bultink Irene E M , Heslinga Maaike , van Tuyl Lilian H , van Vollenhoven Ronald F , Voskuyl Alexandre E 
Published: October 2018

Abstract

Objective
To investigate the relationship between remission and health-related quality of life (HRQoL) in patients with SLE in a longitudinal observational cohort.

Methods
HRQoL was measured at cohort visits using the physical and mental component score (PCS and MCS, respectively) of the Short Form 36 questionnaire. Definitions of Remission in SLE remission categories (no remission/remission on therapy/remission off therapy) were applied. Determinants of PCS and MCS were identified with simple linear regression analyses. Association between remission and HRQoL was assessed using generalized estimating equation models.

Results
Data from 154 patients with 2 years of follow-up were analysed. At baseline 60/154 (39.0%) patients were in either form of remission. Patients in remission had higher Short Form 36 scores in all subdomains compared with patients not in remission. PCS was positively associated with remission and employment, and negatively associated with SLICC damage index, ESR, medication, patient global assessment and BMI. MCS was positively associated with Caucasian ethnicity and negatively associated with patient global assessment. In generalized estimating equation analysis, a gradual and significant increase of PCS was observed from patients not in remission (mean PCS 36.0) to remission on therapy (41.8) to remission off therapy (44.8). No significant difference in MCS was found between remission states.

Conclusion
we show a strong and persistent association between remission and PCS, but not MCS. These results support the relevance (construct validity) of the Definition of Remission in SLE remission definitions and the further development of a treat-to-target approach in SLE.
Challenges and Opportunities in Documenting the Recent History of Public Health: The Health of Bristol after 1948
Authors: Evans David 
Published: October 2018

Summary
How do you find the sources to write the history of the health of a city, particularly for the late twentieth century and into the digital age? This article explores this challenge in the case of the city of Bristol in the United Kingdom during the period from the creation of the National Health Service (NHS) in 1948, through the transfer of the public health function from local government to the NHS in 1974 and up until the return of public health back to local government in 2013. The aims of the article are to scope the extant paper and digital official and academic documentary sources for the history of public health in the city, to critically assess the availability and completeness of the sources and to reflect on the challenges and opportunities of integrating earlier paper records with more recent digital ones.
Fixation of Anteromedial Coronoid Facet Fractures: A Biomechanical Evaluation of Plated Versus Screw Constructs
Authors: Morellato John , Louati Hakim , Desloges William , Papp Steven , Pollock J. Whitcomb 
Published: October 2018

Objective:
To examine the stability of plate (locking and non–) versus screw constructs in the fixation of these fractures.

Methods:
An anteromedial coronoid facet fracture (OTA/AO type 21–B1, O'Driscoll type 2, subtype 3) was simulated in 24 synthetic ulna bones that were then assigned to 3 fracture fixation groups: non–locking plate, locking plate (LP), or screw fixation. Each construct was first cycled in tension (through a simulated medial collateral ligament) and then in compression. They were then loaded to failure (displacement >2 mm). Fracture fragment displacement was recorded with an optical tracking system.

Results:
During tension testing, a mean maximum fragment displacement of 12 ± 13 and 14 ± 9 μm was seen in the locking and non–locking constructs, respectively. There was no difference in fragment motion between the plated constructs. All screw-only fixed constructs failed during the tension protocol. During compression testing, the mean maximum fragment displacement for the screw-only construct (64 ± 79 μm) was significantly greater than locking (9 ± 5 μm) and non–locking constructs (10 ± 9 μm). During load to failure testing, the maximum load to failure in the screw-only group (316 ± 83 N) was significantly lower than locking (650.4 ± 107 N) and non–locking constructs (550 ± 76 N). There was no difference in load to failure between the plated groups.

Conclusion:
Fixation of anteromedial coronoid fractures (type 2, subtype 3) is best achieved with a plating technique. Although LPs had greater stiffness, they did not offer any advantage over conventional non-LPs with respect to fracture fragment displacement in this study.

Clinical Relevance:
Isolated screw fixation showed inferior stability when compared with plate constructs for these fractures. This could result in loss of fracture reduction leading to instability and posttraumatic arthrosis.
Clinical Characteristics of Infective Endocarditis in Children
Authors: Kelchtermans Jelte , Grossar Lorenz , Eyskens Benedicte , Cools Bjorn , Roggen Mieke , Boshoff Derize , Louw Jacoba , Frerich Stefan , Veloso Tiago Rafael , Claes Jorien , Ditkowski Bartosz , Rega Filip , Meyns Bart , Gewillig Marc , Heying Ruth 
Published: October 2018

Background:
Infective endocarditis (IE) remains a diagnostic and therapeutic challenge associated with high morbidity and mortality. We evaluated the microbial profile and clinical manifestation of IE in children.

Methods:
A retrospective study examining pediatric IE cases treated between 2000 and 2017 at the Department of Pediatric Cardiology, KU Leuven, was conducted. Clinical presentation, treatment, complications, outcome of IE, underlying microorganisms and congenital heart defects were reviewed.

Results:
Fifty-three patients were diagnosed with IE. Overall, 19 patients (36%) required cardiac surgery. Seven patients (13%) died. Eighty-seven percent of patients had an underlying congenital cardiac defect. Eighteen (34%) children presented with prosthetic graft IE. A causative organism was found in 49 (92%) cases: viridans group streptococci were identified in 17 (32%), Staphylococcus aureus in 13 (25%) and coagulase-negative staphylococci in 11 (20%) children. Community-acquired (CA) IE increased significantly from 8 (33%) cases in 2000–2007 to 20 (74%) cases in 2008–2017 (P < 0.01). Even with viridans streptococci being significantly more prevalent in the CA group (P < 0.01), we did not observe an increase of streptococcal IE from 2008 to 2017. Seventeen (32%) patients presented with hospital-acquired IE during the first year of life with 14 (82%) children after surgery and a prevalence of coagulase-negative staphylococci (53%).

Conclusions:
The incidence of pediatric IE was similar over the investigated time period with a shift toward CA IE. Streptococci and staphylococci accounted for the majority of cases in both periods. Awareness of IE and its prevention is crucial in patients after implantation of prosthetic grafts.
Natural history of pain associated with melanoma surgery
Authors: Slagelse Charlotte , Munch Troels , Glazer Clara , Greene Kaitlin , Finnerup Nanna Brix , Kashani-Sabet Mohammed , Leong Stanley P. , Petersen Karin Lottrup , Rowbotham Michael C. 
Published: October 2018

Abstract

Introduction:
After excision of a primary malignant melanoma (MM), treatment of stage IB or higher MM consists of sentinel lymph node biopsy (SLNB). If malignant cells are identified, a complete lymph node dissection (CLND) can be performed.

Objective:
To determine the natural history of pain and sensory changes after MM surgery.

Methods:
We prospectively followed 39 patients (29 SLNB-only, 2 CLND-only, and 8 CLND preceded by SLNB) from before inguinal or axillary surgery through 6 months after surgery on measures of pain intensity, sensory symptoms, allodynia, and questionnaires of anxiety, depression, and catastrophizing.

Results:
No patient had pain preoperatively. Ten days after surgery, 35% had surgical site pain after SLNB-only compared with 90% after CLND (P < 0.003); clinically meaningful pain (Visual Analogue Scale ≥ 30 mm/100 mm) was reported by 3% of patients after SLNB-only compared with 40% after CLND (P < 0.001). At 6 months, all SLNB-only patients were pain-free. By contrast, 4 of 7 in the SLNB + CLND group still had pain (P < 0.002). At 6 months, symptoms of altered sensation or numbness were reported by 32% and 42% of SLNB-only patients, and by 67% and 67% of patients undergoing CLND surgery (both P > 0.05).

Conclusion:
Acute pain is more common after CLND surgery. Undergoing SLNB followed by more invasive CLND surgery may increase the likelihood of pain at 6 months. Persistent sensory symptoms typical of those associated with nerve injury are more common after CLND. Surgery for MM is a good model for studying the natural history of postsurgical pain and sensory changes.
Lidocaine Use in Vaginal Surgery and Risk of Toxicity
Authors: Willis-Gray Marcella G. , Husk Katherine E. , Brueseke Taylor J. , Connolly AnnaMarie , Geller Elizabeth J. 
Published: October 2018

Objectives
The primary objective of this study was to compare the amount of lidocaine administered for vaginal reconstruction with versus without hysterectomy. The secondary objective was to assess the risk of lidocaine toxicity.

Methods
This retrospective cohort study compares lidocaine dose in 2 cohorts: women who underwent vaginal hysterectomy with additional vaginal reconstruction (VH + VR) versus those who underwent vaginal reconstruction without hysterectomy (VR only). Total intraoperative lidocaine dose included the intravenous dose from anesthesia and the vaginally injected dose from the surgeon. The risk of toxicity was defined as total dose greater than 7 mg/kg. The primary outcome was the difference in total lidocaine dose for VH + VR versus VR only.

Results
Among 372 women included, 140 (37.6%) were in the VH + VR group, and 232 (62.4%) in the VR-only group. For the primary outcome of total lidocaine dose between groups, VH + VR received more total lidocaine than did VR only (228 ± 105 vs 168 ± 78 mg, P < 0.001). This difference was due to the vaginal lidocaine dose (P < 0.001), with no significant difference in the intravenous lidocaine dose (P = 0.68). In a logistic regression model controlling for age, anesthesia type, sling, and anterior repair, posterior repair, and anesthesia type, VH remained an independent risk factor for increased lidocaine dose (P < 0.001). Two women received a toxic dose of lidocaine, and both were in the VH + VR group.

Conclusions
Women undergoing vaginal hysterectomy with additional vaginal reconstructive procedures are more likely to receive a higher dose of lidocaine compared with women undergoing vaginal reconstruction alone. The risk of lidocaine toxicity is increased with concomitant procedures.
Estimating interaction credit for trophic rewilding in tropical forests
Authors: Marjakangas Emma-Liina , Genes Luísa , Pires Mathias M. , Fernandez Fernando A. S. , de Lima Renato A. F. , de Oliveira Alexandre A. , Ovaskainen Otso , Pires Alexandra S. , Prado Paulo I. , Galetti Mauro 
Published: October 2018

Trophic rewilding has been suggested as a restoration tool to restore ecological interactions and reverse defaunation and its cascading effects on ecosystem functioning. One of the ecological processes that has been jeopardized by defaunation is animal-mediated seed dispersal. Here, we propose an approach that combines joint species distribution models with occurrence data and species interaction records to quantify the potential to restore seed-dispersal interactions through rewilding and apply it to the Atlantic Forest, a global biodiversity hotspot. Using this approach, we identify areas that should benefit the most from trophic rewilding and candidate species that could contribute to cash the credit of seed-dispersal interactions in a given site. We found that sites within large fragments bearing a great diversity of trees may have about 20 times as many interactions to be cashed through rewilding as small fragments in regions where deforestation has been pervasive. We also ranked mammal and bird species according to their potential to restore seed-dispersal interactions if reintroduced while considering the biome as a whole and at finer scales. The suggested approach can aid future conservation efforts in rewilding projects in defaunated tropical rainforests.
This article is part of the theme issue ‘Trophic rewilding: consequences for ecosystems under global change’.
Trophic rewilding as a climate change mitigation strategy?
Authors: Cromsigt Joris P. G. M. , te Beest Mariska , Kerley Graham I. H. , Landman Marietjie , le Roux Elizabeth , Smith Felisa A. 
Published: October 2018

The loss of megafauna at the terminal Pleistocene has been linked to a wide range of Earth-system-level changes, such as altered greenhouse gas budgets, fire regimes and biome-level vegetation changes. Given these influences and feedbacks, might part of the solution for mitigating anthropogenic climate change lie in the restoration of extant megafauna to ecosystems? Here, we explore the potential role of trophic rewilding on Earth's climate system. We first provide a novel synthesis of the various ways that megafauna interact with the major drivers of anthropogenic climate change, including greenhouse gas storage and emission, aerosols and albedo. We then explore the role of rewilding as a mitigation tool at two scales: (i) current and near-future opportunities for national or regional climate change mitigation portfolios, and (ii) more radical opportunities at the global scale. Finally, we identify major knowledge gaps that complicate the complete characterization of rewilding as a climate change mitigation strategy. Our perspective is urgent since we are losing the Earth's last remaining megafauna, and with it a potential option to address climate change.
This article is part of the theme issue ‘Trophic rewilding: consequences for ecosystems under global change’.
SimpactCyan 1.0: An Open-source Simulator for Individual-Based Models in HIV Epidemiology with R and Python Interfaces
Authors: Liesenborgs Jori , Hendrickx Diana M , Kuylen Elise , Niyukuri David , Hens Niel , Delva Wim 
Published: October 2018

ABSTRACTSimpactCyan is an open-source simulator for individual-based models in HIV epidemiology. Its core algorithm is written in C++ for computational efficiency, while the R and Python interfaces aim to make the tool accessible to the fast-growing community of R and Python users. Transmission, treatment and prevention of HIV infections in dynamic sexual networks are simulated by discrete events. A generic “intervention” event allows model parameters to be changed over time, and can be used to model medical and behavioural HIV prevention programmes. First, we describe a more efficient variant of the modified Next Reaction Method that drives our continuous-time simulator. Next, we outline key built-in features and assumptions of individual-based models formulated in SimpactCyan, and provide code snippets for how to formulate, execute and analyse models in SimpactCyan through its R and Python interfaces. Lastly, we give two examples of applications in HIV epidemiology: the first demonstrates how the software can be used to estimate the impact of progressive changes to the eligibility criteria for HIV treatment on HIV incidence. The second example illustrates the use of SimpactCyan as a data-generating tool for assessing the performance of a phylodynamic inference framework.
Postmarketing commitments for novel drugs and biologics approved by the US Food and Drug Administration: a cross-sectional analysis
Authors: Wallach Joshua D , Luxkaranayagam Anita T , Dhruva Sanket S , Miller Jennifer E , Ross Joseph S 
Published: October 2018

AbstractBackgroundPostmarketing commitments are clinical studies that drug sponsors agree to conduct at the time of FDA approval, but which are not required by statute or regulation. The objective of this study was to determine the characteristics, completion, and dissemination of postmarketing commitments agreed upon by sponsors at first FDA approval.MethodsWe performed a cross-sectional analysis of postmarketing commitments for new drugs and biologics approved 2009-2012. Using public FDA documents, ClinicalTrials.gov, and Scopus, we determined postmarketing commitments and their characteristics known at the time of FDA approval; number of postmarketing commitments subject to reporting requirements, for which FDA is required to make study status information available to the public (“506B studies”), and their statuses; and rates of registration and results reporting on ClinicalTrials.gov and publication in peer-reviewed journals for all clinical trials, with follow-up through July 2018.ResultsAmong 110 novel drugs and biologics approved by the FDA between 2009-2012, 61 (55.5%) had at least one postmarketing commitment at the time of first approval. Of 331 total postmarketing commitments, 271 (81.9%) were non-human subjects research, predominantly chemistry, manufacturing, and controls studies; 49 (14.8%) were clinical trials (33 new and 16 ongoing trials for which follow-up results would be reported). Study descriptions for the new clinical trials often lacked information to establish study design features. Of the 89 (26.9%) 506B studies subject to public reporting requirements, of which 42 were clinical trials, 59 (66.3%) did not have an up-to-date status provided by FDA. Nearly all new clinical trials (28 of 31, 90.3%) were registered on ClinicalTrials.gov; of the 23 registered trials that were completed or terminated, 22 (95.7%) had reported results. Only half (14 of 29, 48.3%) of completed or terminated clinical trials, registered or unregistered, were published in peer-reviewed journals. Conclusions: The majority of postmarketing commitments agreed to by sponsors at the time of FDA approval for novel drugs and biologics approved between 2009-2012 were chemistry, manufacturing, and controls studies. While only 15% were clinical trials, these trials were nearly always registered with reported results on ClinicalTrials.gov. However, despite FDA public reporting requirements, up-to-date study status information was often unavailable for 506B studies.
LRRK2 exonic variants associated with Parkinson’s disease augment phosphorylation levels for LRRK2-Ser1292 and Rab10-Thr73
Authors: Christensen Kenneth V. , Hentzer Morten , Oppermann Felix S. , Elschenbroich Sarah , Dossang Pamela , Thirstrup Kenneth , Egebjerg Jan , Williamson Douglas S. , Smith Garrick P. 
Published: October 2018

AbstractLeucine-rich repeat kinase 2 (LRRK2) is associated to Parkinson’s disease (PD). The most common form of LRRK2 PD is caused by the G2019S variant. Besides G2019S, eight other LRRK2 variants causing familial PD also have amino acid substitutions located in a LRRK2 enzymatic domainsuggesting that enzymatic activity is at the core of mechanisms underlying disease risk. Common LRRK2 polymorphic risk variations such as G2385R, A419V, R1628 and M1646T all reside in other LRRK2 domains. Prior knowledge is limited on how these variants influence LRRK2 function. To investigate the impact on enzymatic function of both rare and common LRRK2 variation a comprehensive profiling of nineteen LRRK2 exonic variants was pursued. Six LRRK2 phosphorylation sites were identified by mass spectrometry. Besides already known phosphorylation sites such as Ser910, Ser935, Ser955, Ser973 and Ser1292 also Thr826 was confirmed by a targeted MRM assay as a LRRK2 phosphorylation site in mammalian cells. Phosphorylation site occupancy for all six LRRK2 sites was obtained but no obvious correlation to risk of disease was found. Instead, application of phospho-specific antibodies targeting LRRK2 phosphorylation sites confirmed that autophosphorylation at Ser1292 was significantly increased for all disease-causing variants whereas no significant differences could be observed for the common intermediate risk variants. Recently, Rab10 and Rab12 have been shown to be bona fide LRRK2 substrates and we find that both rare and common LRRK2 exonic variants augment the phosphorylation of Rab10. This was not observed with Rab12. Furthermore, the protective variant N551K has reduced Rab10 phosphorylation compared to LRRK2 WT. This was not observed with the protective variant R1398H. Our findings support the hypothesis that increased LRRK2 kinase function is associated with increased PD risk but also highlights the need for more sensitive tools for detection of increases in kinase activity in carriers of LRRK2 PD risk variants.AbbreviationsPDParkinson’s diseaseLRRK2leucine-rich repeat kinase 2MRMmultiple mass spectrometryMSmass spectrometryLC-MSliquid chromatography mass spectrometryLODlimit of detectionMAFminor allele frequencyCV%coefficient of variationSDS-PAGESDS-polyacrylamide gel electrophoresisRocRas of complexCORC-terminal of RocPRLpleomorphic risk loci.
Chlamydia muridarum infection differentially changes smooth muscle contractility and responses to prostaglandins in uterus and cervix
Authors: Lee Jia Ming , Mayall Jemma R. , Chevalier Anne , Helden Dirk Van , Horvat Jay C. , Hansbro Philip M. , Jobling Philip 
Published: October 2018

AbstractChlamydia trachomatis infection is a primary cause of reproductive tract diseases including chronic pelvic pain and infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. This study characterized the physiological activity of the uterus and the cervix in a Chlamydia muridarum (Cmu) mouse model of reproductive tract infection. Uterine or cervix smooth muscle contractility, responses to oxytocin or prostaglandins (PGF2α and PGE2) and mRNA expression of oxytocin and PG receptors were assessed 14 days post infection. Cmu infection did not affect the contractions of the uterine horn but significantly decreased the contraction amplitude of the cervix. Cmu infection did not alter the responses of uterine horn or cervix to oxytocin, however PGF2α induced contractions of the uterine horn, but not the cervix, were significantly increased following Cmu infection. PGE2 contraction amplitude in both the uterine horn and cervix was unaffected by Cmu infection. An upregulation of Ptgfr and a down-regulation of Ptegr4 mRNA expression was observed in the uterine horn following Cmu infection. These results indicate that Cmu infection alters contractility and prostaglandin signalling in the female reproductive tract but the effects are localised to specific regions.