bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacokinetics of abacavir and lamivudine in severely malnourished human immunodeficiency virus‐infected children in relation to treatment outcomes
Authors: Archary Moherndran , Mcllleron Helen , Bobat Raziya , LaRussa Philip , Sibaya Thobekile , Wiesner Lubbe , Hennig Stefanie
Published: May 2019

Aims

Describe the pharmacokinetics (PK) of the antiretroviral drugs abacavir and lamivudine in malnourished paediatric patients and relate to viral load outcomes after 12 and 48 weeks of treatment.

Methods

Severely malnourished human immunodeficiency virus‐infected children were randomized to early (within 14 days) or delayed (after nutritional recovery) initiation of antiretroviral treatment (ART) using World Health Organization weight‐band dosages. Abacavir and lamivudine concentrations were measured as a secondary objective on day 1 and day 14 and patients were followed‐up to week 48. Population PK of abacavir and lamivudine were described using NONMEM.

Results

In total, 623 abacavir and 627 lamivudine concentrations were collected from 75 paediatric patients aged 0.1–10.8 (median 1.4) years. Abacavir PK was described by a 2‐compartment model, patients randomized to early ART showed increased bioavailability of 31%. Apparent clearance (CL/F, L/h/7 kg) of abacavir increased from day 1 to day 14 from 3.33 (95% confidence interval 2.71–4.12) to 5.86 (95% confidence interval 4.78–7.3). A 1‐compartment model described lamivudine PK, variability on CL/F was explained by maturation with age, with age at half‐matured CL/F being 4 months. For both drugs allometrically scaled total body weight was related to CL/F and apparent volume of distribution. PK exposure did not correlate with virological outcomes or death at 12 or 48 weeks.

Conclusion

Increases in Abacavir's CL/F between day 1 to day 14, bioavailability and PK variability with early start of ART was found in this cohort of severely malnourished children; however, these changes did not influence virological outcomes. The study supports the use of weight‐band dosage tables.
Using computer‐based cognitive mapping to improve students' divergent thinking for creativity development
Authors: Sun Meng , Wang Minhong , Wegerif Rupert
Published: May 2019

Creativity is increasingly considered to be an important goal of education. While creativity can be influenced by many noncognitive factors (eg, personality and motivation), creative thinking remains the most important source of creativity. Creative thinking combines several cognitive processes leading to the generation and selection of new and useful ideas or solutions. Divergent thinking or the ability to generate a range of alternative ideas, is a necessary component of creative thinking. Research has explored cognitive strategies to activate divergent thinking. However, such strategies are often abstract and difficult to implement. This study proposes a computer‐based cognitive mapping approach to improving divergent thinking as a response to this challenge. The approach enables students to build a computer‐based cognitive map that can foster divergent thinking by associating unrelated concept, object or situation (COS), by decomposing a COS into rich details for viewing it from divergent perspectives, and by combining and changing COSs. A quasi‐experiment was conducted with high school students. The results have shown promising effects of the approach on improving students' performance and perceived competence in divergent thinking.

Practitioner Notes

What is already known about this topic

Divergent thinking is an important part of the cognitive processes that may lead to creativity.

Divergent thinking can be enhanced by training in cognitive strategies, but these strategies involve complex cognitive processes that are abstract and difficult to implement.

Cognitive mapping can facilitate complex thinking and cognitive processes.

What this paper adds

This study proposes a computer‐based cognitive mapping approach as a divergent thinking tool that may help students visualize the process of applying divergent thinking strategies (association, decomposition, and combination and adjustment) when performing creativity‐related tasks.

The approach is effective in improving high school students' divergent thinking performance in terms of idea fluency, flexibility and originality, in addition to perceived competence in divergent thinking.

Implications for practice and/or policy

It is important to provide learners with effective thinking tools that facilitate the complex cognitive processes of applying divergent thinking strategies.

Divergent thinking processes can be facilitated by associating unrelated concept, object or situation (COS), by decomposing a COS into rich details for viewing it from divergent perspectives, and by combining and changing COSs.
Navigating the principle of open court in the digital age: The more things change, the more they stay the same
Authors: Puddister Kate , Small Tamara A.
Published: May 2019

The belief that courts should be open to the public is a guiding principle of the Canadian legal system. This article examines the principle of open court in the digital age by analyzing policies governing live text‐based communication in Canadian courtrooms. We argue that courts have and have not responded to the changing digital landscape. While Canadian journalists have the ability to use live text‐based communication in courts, the general public does not despite new affordances provided to them by digital technologies. This article explores the tensions between administrative judicial independence, open court, and digital technology.
Trabecular bone score and bone remodelling markers identify perimenopausal women at high risk of bone loss
Authors: Gutierrez‐Buey Gala , Restituto Patricia , Botella Sonsoles , Monreal Ignacio , Colina Inmaculada , Rodríguez‐Fraile Macarena , Calleja Amparo , Varo Nerea
Published: May 2019

Context

Bone loss is accelerated in the late perimenopause and early menopause. The date of the final menstrual period cannot be stated until 1 year after it has ended, and at that time, most of the rapid bone loss phase will have elapsed. Therefore, early detection of bone loss is crucial.

Objectives

To evaluate the utility of bone turnover markers (BTM) to identify the women who are more likely to lose more bone mass during the transition to menopause and quantify the loss of bone quality measured by trabecular bone score (TBS).

Design, patients and setting

Sixty‐four healthy premenopausal women, mean age between 44 and 57 years old, were enrolled and followed up for 5 years. Clinical features, lifestyle, bone densitometry, TBS and BTM (CTX, P1NP and osteocalcin) were measured at baseline and follow‐up.

Results

All women had densitometrically normal bone at the time of enrolment. After 5 years, 48.4% had normal bone mineral density, 45.8% low bone mass and 6.3% osteoporosis. Women with osteopenia/osteoporosis at follow‐up had higher CTX and P1NP at enrolment compared with women with densitometrically normal bone. The areas under the curve for the prediction of low bone mass or osteoporosis were 0.69 (P = 0.011) for P1NP, 0.69 for CTX (P = 0.013) and 0.77 (P 0.001) for OC. A significant correlation was found between P1NP increase after 5 years and the decrease in lumbar bone density (r = −0.383, P = 0.002). At baseline, 7 (10.9%) women had deteriorated microarchitecture (TBS < 1.3). Three of these women developed osteoporosis and four osteopenia at follow‐up.

Conclusions

Women with higher P1NP and CTX and lower TBS at baseline had lower BMD in the transition to menopause suggesting these novel tools could have potential use in identifying women at high risk of rapidly decreasing bone mass.
Exploring training dental implant placement using computer‐guided implant navigation system for predoctoral students: A pilot study
Authors: Golob Deeb Janina , Bencharit Sompop , Carrico Caroline K. , Lukic Marija , Hawkins Daniel , Rener‐Sitar Ksenija , Deeb George R.
Published: May 2019

Introduction

Recent computer‐guided dynamic navigation systems promise a novel training approach for implant surgery. This study aimed to examine learning progress in placement of dental implants among dental students using dynamic navigation on a simulation model.

Materials and Methods

Senior students with no implant placement experience were randomly assigned five implant placement attempts involving either three maxillary or four mandibular implants distributed in the anterior/posterior, and left/right segments. Implant placement was planned using a Navident Dynamic Guidance system. Surgical time was recorded. Horizontal, vertical and angulation discrepancies between the planned and placed implant positions were measured using superimposed CBCT scans. Data were analysed with repeated measures regression with Tukey's adjusted pairwise comparisons (α = 0.05).

Results

Fourteen students participated, with a mean age of 26.1 years and equal males and females. Mean time for implant placement was associated with attempt number (P < 0.001), implant site (P = 0.010) and marginally related to gender (P = 0.061). Students had a significant reduction in time from their first attempt to their second (10.6 vs 7.6 minutes; adjusted P < 0.001) then plateaued. Overall 3D angulation (P < 0.001) and 2D vertical apex deviation (P = 0.014) improved with each attempt, but changes in lateral 2D (P = 0.513) and overall 3D apex deviations (P = 0.784) were not statistically significant. Implant sites were associated with lateral 2D, 2D vertical and overall 3D apex deviation (P < 0.001).

Discussion

Males were marginally faster than females, had slightly lower overall 3D angulation, and reported higher proficiency with video games. Novice operators improved significantly in speed and angulation deviation within the first three attempts of placing implants using dynamic navigation.

Conclusion

Computer‐aided dynamic implant navigation systems can improve implant surgical training in novice population.
Teachers and researchers in collaboration. A possibility to overcome the research‐practice gap?
Authors: Runesson Kempe Ulla
Published: May 2019

Taking as its point of departure the discussion about the disconnection between research and practice, this article presents learning study as a research approach to overcoming this gap. Learning study has commonalities with design research and lesson study, but is a teacher‐researcher collaboration where both have a common object of research. Thus, it is research with teachers, rather than on teachers and focuses on constructing knowledge concerning objects of learning as well as teaching‐learning relationships. The focus of the research collaboration is professional problems related to the object of learning that teachers encounter in their everyday practice. The process is guided by a theory of learning and pedagogy—the variation theory. The knowledge product of learning study is a theoretical description of what must be learned in order to develop a specific capability. Examples of knowledge contributions from learning study are given and it is suggested that such knowledge can be considered to be public knowledge that can be shared, used and developed by other teachers in other contexts. Furthermore, it is suggested that there are specific features of learning study that make it a research approach that may strengthen connections between research and practice.
Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters—a randomized, double‐blind, placebo‐controlled trial
Authors: Detyniecki Kamil , Van Ess Peter J. , Sequeira David J. , Wheless James W. , Meng Tze‐Chiang , Pullman William E.
Published: May 2019

Objective

To evaluate the safety and efficacy of a novel formulation of midazolam administered as a single‐dose nasal spray (MDZ–NS) in the outpatient treatment of patients experiencing seizure clusters (SCs).

Methods

This was a phase III, randomized, double‐blind, placebo‐controlled trial (ClinicalTrials.gov NCT01390220) with patients age ≥12 years on a stable regimen of antiepileptic drugs. Following an in‐clinic test dose phase (TDP), patients entered an outpatient comparative phase (CP) and were randomized (2:1) to receive double‐blind MDZ–NS 5 mg or placebo nasal spray, administered by caregivers when they experienced an SC. The primary efficacy end point was treatment success (seizure termination within 10 minutes and no recurrence 10 minutes to 6 hours after trial drug administration). Secondary efficacy end points were proportion of patients with seizure recurrence 10 minutes to 4 hours, and time‐to‐next seizure >10 minutes after double‐blind drug administration. Safety was monitored throughout.

Results

Of 292 patients administered a test dose, 262 patients were randomized, and 201 received double‐blind treatment for an SC (n = 134 MDZ–NS, n = 67 placebo, modified intent‐to‐treat population). A significantly greater proportion of MDZ–NS‐ than placebo‐treated patients achieved treatment success (53.7% vs 34.4%; P = 0.0109). Significantly, fewer MDZ–NS‐ than placebo‐treated patients experienced seizure recurrence (38.1% vs 59.7%; P = 0.0043). Time‐to‐next seizure analysis showed early separation (within 30 minutes) between MDZ–NS and placebo that was maintained throughout the 24‐hour observation period (21% difference at 24 hours; P = 0.0124). Sixteen patients (5.5%) discontinued because of a treatment‐emergent adverse event (TEAE) during the TDP and none during the CP. During the CP, 27.6% and 22.4% of patients in the MDZ–NS and placebo groups, respectively, experienced ≥1 TEAE.

Significance

MDZ–NS was superior to placebo in providing rapid, sustained seizure control when administered to patients experiencing an SC in the outpatient setting and was associated with a favorable safety profile.
Similar efficacy and safety of dolutegravir between age groups of HIV‐1‐infected paediatric and young adult patients aged 5 years and older
Authors: Frange P , Avettand‐Fenoel V , Veber F , Blanche S
Published: May 2019

Objectives

The aim of the study was to carry out a comparison of the safety and efficacy of dolutegravir‐based regimens among age groups of HIV‐1‐infected paediatric and young adult patients.

Patients and methods

This retrospective monocentric study included 109 patients infected since childhood who began receiving dolutegravir between January 2014 and December 2017. The patients were divided into three groups according to age at the time of dolutegravir initiation: 5–11, 12–17 and 18–25 years old. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) < 50 HIV‐1 RNA copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline), and maintaining virological suppression (PVL < 50 copies/mL) until the last follow‐up visit (for all patients).

Results

Most of the subjects were antiretroviral‐experienced (91.7%) and virologically suppressed at baseline (66.7%, 54.9% and 56.0% in the 5–11, 12–17 and 18–25 year age groups, respectively). Median follow‐up was 24 months (range 6–54 months). Sustained virological success throughout follow‐up was observed in 79.8% of patients, with similar rates among age groups (87.9%, 72.5% and 84.0%, respectively; P = 0.22). With reinforced measures to improve adherence, undetectable PVL was obtained at the last visit in 88.1% of patients, with similar proportions among age groups (93.9%, 84.3% and 88.0%, respectively; P = 0.51). No emergence of resistance mutations was observed in the 22 patients with virological failure. Dolutegravir was well tolerated; only one patient stopped treatment for severe drug‐related side effects.

Conclusions

The virological efficacy and safety of dolutegravir were similar among the three age groups. Because of its high genetic barrier to resistance, dolutegravir could be especially useful in the paediatric population, in which the risk of poor treatment adherence is high.
Impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma
Authors: Kobayashi Masaki , Tanaka Hajime , Tateishi Ukihide , Numao Noboru , Yonese Junji , Ito Masaya , Koga Fumitaka , Fukushima Hiroshi , Uehara Sho , Yoshida Soichiro , Yokoyama Minato , Ishioka Junichiro , Matsuoka Yoh , Saito Kazutaka , Kihara Kazunori , Fujii Yasuhisa
Published: May 2019

Objectives

To evaluate the impact of fluorodeoxyglucose uptake on positron emission tomography/computed tomography on chemosensitivity and survival in patients with metastatic urothelial carcinoma.

Methods

The present study assessed 51 metastatic urothelial carcinoma patients undergoing fluorodeoxyglucose positron emission tomography/computed tomography before first‐line systemic chemotherapy. Fluorodeoxyglucose uptake in metastases was evaluated using the maximum standardized uptake value, which was measured for all eligible lesions, and the highest value among the maximum standardized uptake value measurements in each case was defined as the highest maximum standardized uptake value. The associations between the highest maximum standardized uptake value and objective response rate to chemotherapy, progression‐free survival or cancer‐specific survival were analyzed. For cancer‐specific survival, the C‐index was compared between multivariate models that incorporated predictors in the Bajorin model including the Karnofsky performance status and the presence of visceral metastasis, and the Apolo model additionally including hemoglobin and albumin levels, with/without the highest maximum standardized uptake value.

Results

The median age was 69 years. The Karnofsky performance status was ≥80% for all patients. Visceral metastasis was observed in 12 patients (24%). The objective response rate, median progression‐free survival and median cancer‐specific survival were 61%, 9 and 26 months in the entire cohort, respectively. The higher highest maximum standardized uptake value was significantly associated with a lower objective response rate, shorter progression‐free survival and shorter cancer‐specific survival (P = 0.01, <0.001 and 0.004, respectively). On multivariate analyses, the highest maximum standardized uptake value was an independent predictor for all end‐points. In the multivariate models for cancer‐specific survival, the C‐index improved from 0.559 to 0.601 and from 0.604 to 0.652 by adding the highest maximum standardized uptake value to the parameter set of the Bajorin model and Apolo model, respectively.

Conclusions

Higher fluorodeoxyglucose uptake in metastases was significantly and independently associated with poor chemosensitivity and worse survival outcomes. Fluorodeoxyglucose positron emission tomography/computed tomography might aid in patient counseling and treatment decisions for metastatic urothelial carcinoma patients.
Beyond memory T cells: mechanisms of protective immunity to tuberculosis infection
Authors: Steigler Pia , Verrall Ayesha J , Kirman Joanna R
Published: May 2019

Tuberculosis (TB) is a serious infectious disease caused by infection with Mycobacterium tuberculosis, and kills more people annually than any other single infectious agent. Although a vaccine is available, it is only moderately effective and an improved vaccine is urgently needed. The ability to develop a more effective vaccine has been thwarted by a lack of understanding of the mechanism of vaccine‐induced immune protection. Over recent decades, many novel TB vaccines have been developed and almost all have aimed to generate memory CD4 T cells. In this review, we critically evaluate evidence in the literature that supports the contention that memory CD4 T cells are the prime mediators of vaccine‐induced protection against TB. Because of the lack of robust evidence supporting memory CD4 T cells in this role, the potential for B‐cell antibody and “trained” innate cells as alternative mediators of protective immunity is explored.
Barriers to recovery‐focused care within therapeutic relationships in nursing: Attitudes and perceptions
Authors: Harris Barbara , Panozzo Gina
Published: May 2019

There are numerous barriers to the therapeutic relationship between nurses and persons with schizophrenia, such as time constraints, communication issues and the requirements of practice policies. The main point of this paper is that the nature of these barriers is such that the nurse may not conceptualize these as barriers or be aware of how his or her responses to these can further entrench existing barriers to relationship or create new ones. If the nurse is not aware of how he or she responds to time pressure, frustration or lack of clarity of practice policy and address this, there is a risk that the patient may perceive the nurse's actions as lacking in care, presence or involvement. As consumers increasingly embrace recovery approaches to mental health that prioritize therapeutic activities within the context of collaborative relationship, psychiatric nurses, with a long tradition of therapeutic relationship, can rise to meet them. It is suggested here that this can only occur if nurses are fully aware of barriers to relationship, their responses to these and the impact of these on relationship with patients. Suggestions for educational and empirical work to further raise awareness and promote understanding of this process are provided.
Computational comparisons of different formulations for the Stackelberg minimum spanning tree game
Authors: Labbé Martine , Pozo Miguel A. , Puerto Justo
Published: May 2019

Let be a given graph whose edge set is partitioned into a set R of red edges and a set B of blue edges, and assume that red edges are weighted and contain a spanning tree of G. Then, the Stackelberg minimum spanning tree game (StackMST) is that of pricing (i.e., weighting) the blue edges in such a way that the total weight of the blue edges selected in a minimum spanning tree of the resulting graph is maximized. In this paper, we present different new mathematical programming formulations for the StackMST based on the properties of the minimum spanning tree problem and the bilevel optimization. We establish a theoretical and empirical comparison between these new formulations that are able to solve random instances of 20–70 nodes. We also test our models on instances in the literature, outperforming previous results.
Friends and Allies: LGBT+ Inclusion in Statistics and Data Science
Authors: Thornton Suzanne , Green Brittany , Benn Emma
Published: May 2019

At a conference last year, Suzanne Thornton, Brittany Green and Emma Benn organised a panel session to share advice and recommendations for making the statistics and data science community more inclusive and supportive of gender non-conforming and LGBTQ persons. Here they summarise their discussion in the hope of continuing the conversation
Memory retention of appetitive and aversive conditioning in the damselfish Stegastes fuscus
Authors: Silveira Mayara M. , Ferreira de Souza Jéssica , Pires Moreira Ana L. , Silva Priscila F. , Luchiari Ana C.
Published: May 2019

We compared the memory of damselfish Stegastes fuscus in an aversive and appetitive conditioning task. Fish were trained to associate the sides of the tank that corresponded to the presence of a positive (conspecific presence) or negative (electroshock) stimulus. After two conditioning sessions, they were tested for learning. The fish conditioned to the stimulus were then re‐tested for memory retention after 5, 10 or 15 days. Both the positive and negative rewards were associated with a specific side of the tank, indicating learning ability. Additionally, in both contexts, S. fuscus stored the information learned and showed similar behavioural patterns after 5, 10 and 15 days, suggesting long‐lasting memory. For the ecological context, long lasting memories of social encounters outcomes and negative experiences of threatening situations may confer advantages that ultimately affect fishes’ fitness.
Presence and genetic variability of Piscine orthoreovirus genotype 1 (PRV‐1) in wild salmonids in Northern Europe and North Atlantic Ocean
Authors: Vendramin Niccoló , Cuenca Argelia , Sørensen Juliane , Alencar Anna L. F. , Christiansen Debes H. , Jacobsen Jan A. , Axen Charlotte , Lieffrig François , Ruane Neil M. , Martin Patrick , Sheehan Timothy , Iburg Tine M. , Rimstad Espen , Olesen Niels J.
Published: May 2019

Piscine orthoreovirus genotype 1 (PRV‐1) is widespread in farmed Atlantic salmon (Salmo salar L.) populations in northern Europe, Canada and Chile. PRV‐1 occurs in wild fish in Norway and Canada; however, little information of its geographical distribution in wild populations is currently available, and the effect of PRV‐1 infection in wild populations is currently unknown. In this study, we present the findings of a survey conducted on 1,130 wild salmonids sampled in Denmark, Sweden, Ireland, Faroe Islands, France, Belgium and Greenland between 2008 and 2017. PRV‐1 is reported for the first time in wild salmonids in Denmark, Sweden, Faroe Island and Ireland. The annual PRV‐1 prevalence ranged from 0% in France, Belgium and Greenland to 43% in Faroe Islands. In total, 66 samples tested positive for PRV‐1, including Atlantic salmon broodfish returning to spawn and Atlantic salmon collected at the feeding ground north of Faroe Islands. The phylogenetic analysis of S1 sequences of the PRV‐1 isolates obtained in this survey did not show systematic geographical distribution. This study sheds light on the spread and genetic diversity of the virus identified in populations of free‐living fish and provides rationale for screening wild broodfish used in restocking programmes.
Landscape genomics of an obligate mutualism: Concordant and discordant population structures between the leafcutter antAtta texanaand its two main fungal symbiont types
Authors: Smith Chad C. , Weber Jesse N. , Mikheyev Alexander S. , Roces Flavio , Bollazzi Martin , Kellner Katrin , Seal Jon N. , Mueller Ulrich G.
Published: May 2019

To explore landscape genomics at the range limit of an obligate mutualism, we use genotyping‐by‐sequencing (ddRADseq) to quantify population structure and the effect of host–symbiont interactions between the northernmost fungus‐farming leafcutter antAtta texanaand its two main types of cultivated fungus. Genome‐wide differentiation between ants associated with either of the two fungal types is of the same order of magnitude as differentiation associated with temperature and precipitation across the ant's entire range, suggesting that specific ant–fungus genome–genome combinations may have been favoured by selection. For the ant hosts, we found a broad cline of genetic structure across the range, and a reduction of genetic diversity along the axis of range expansion towards the range margin. This population‐genetic structure was concordant between the ants and one cultivar type (M‐fungi, concordant clines) but discordant for the other cultivar type (T‐fungi). Discordance in population‐genetic structures between ant hosts and a fungal symbiont is surprising because the ant farmers codisperse with their vertically transmitted fungal symbionts. Discordance implies that (a) the fungi disperse also through between‐nest horizontal transfer or other unknown mechanisms, and (b) genetic drift and gene flow can differ in magnitude between each partner and between different ant–fungus combinations. Together, these findings imply that variation in the strength of drift and gene flow experienced by each mutualistic partner affects adaptation to environmental stress at the range margin, and genome–genome interactions between host and symbiont influence adaptive genetic differentiation of the host during range evolution in this obligate mutualism.
Seed and pollen dispersal distances in two African legume timber trees and their reproductive potential under selective logging
Authors: Hardy Olivier J. , Delaide Boris , Hainaut Hélène , Gillet Jean‐François , Gillet Pauline , Kaymak Esra , Vankerckhove Nina , Duminil Jérôme , Doucet Jean‐Louis
Published: May 2019

The natural regeneration of tree species depends on seed and pollen dispersal. To assess whether limited dispersal could be critical for the sustainability of selective logging practices, we performed parentage analyses in two Central African legume canopy species displaying contrasted floral and fruit traits: Distemonanthus benthamianus and Erythrophleum suaveolens. We also developed new tools linking forward dispersal kernels with backward migration rates to better characterize long‐distance dispersal. Much longer pollen dispersal in D. benthamianus (mean distance dp = 700 m, mp = 52% immigration rate in 6 km2 plot, s = 7% selfing rate) than in E. suaveolens (dp = 294 m, mp = 22% in 2 km2 plot, s = 20%) might reflect different insect pollinators. At a local scale, secondary seed dispersal by vertebrates led to larger seed dispersal distances in the barochorous E. suaveolens (ds = 175 m) than in the wind‐dispersed D. benthamianus (ds = 71 m). Yet, seed dispersal appeared much more fat‐tailed in the latter species (15%–25% seeds dispersing >500 m), putatively due to storm winds (papery pods). The reproductive success was correlated to trunk diameter in E. suaveolens and crown dominance in D. benthamianus. Contrary to D. benthamianus, E. suaveolens underwent significant assortative mating, increasing further the already high inbreeding of its juveniles due to selfing, which seems offset by strong inbreeding depression. To achieve sustainable exploitation, seed and pollen dispersal distances did not appear limiting, but the natural regeneration of E. suaveolens might become insufficient if all trees above the minimum legal cutting diameter were exploited. This highlights the importance of assessing the diameter structure of reproductive trees for logged species.
World Workshop on Oral Medicine VII: Immunobiologics for salivary gland disease in Sjögren's syndrome: A systematic review
Authors: Gueiros Luiz A. , France Katherine , Posey Rachael , Mays Jacqueline W. , Carey Barbara , Sollecito Thomas P. , Setterfield Jane , Woo Sook Bin , Culton Donna , Payne Aimee S. , Lodi Giovanni , Greenberg Martin S. , De Rossi Scott
Published: May 2019

Objective

This systematic review evaluated the efficacy of immunobiologics for the management of oral disease in Sjögren's syndrome (SS).

Materials and Methods

MEDLINE®, Embase, Scopus, and the Cochrane Library were searched for evidence on the use of immunobiologics for management of glandular disease in SS. Primary outcomes were xerostomia and salivary gland dysfunction, assessed via visual analogue scales, disease‐specific scales for SS, measurement of salivary flow, ultrasound data, and quality of life measures.

Results

Seventeen studies (11 randomized controlled trials and 6 observational studies) met inclusion criteria. Rituximab showed efficacy in improving salivary gland function but not xerostomia. Abatacept showed promise in improving both xerostomia and salivary flow. Belimumab exhibited long‐term improvement of salivary flow and subjective measures. The novel agent CFZ533 improved both disease activity and patient‐reported indexes.

Conclusions

There is strong evidence pointing to the efficacy of rituximab in the management of oral disease in SS. Future controlled trials may elucidate the efficacy of belimumab and abatacept. The new drug CFZ533 is a promising alternative for the management of SS and its salivary gland involvement. In considering these agents, the promise of efficacy must be balanced against the harmful effects associated with biologic agents.
World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists—Part 1. A methodological guide
Authors: Varoni Elena M. , Bavarian Roxanne , Robledo‐Sierra Jairo , Porat Ben‐Amy Dalit , Wade William G. , Paster Bruce , Kerr Alexander R. , Peterson Douglas E. , Frandsen Lau Ellen
Published: May 2019

Advances in high‐throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven‐step “recipe” for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high‐throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.
World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review
Authors: Pentenero Monica , Bowers Leah M. , Jayasinghe Ruwan , Yap Tami , Cheong Sok Ching , Kerr Alexander R. , Farah Camile S. , Alevizos Ilias
Published: May 2019

Background

Long non‐coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis.

Objectives

To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma.

Methods

PubMed, Scopus and Web of Science were used as search engines. Clinical, full‐length, English language studies were included. PRISMA‐ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival.

Results

Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs.

Conclusions

Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.
World Workshop of Oral Medicine VII: A systematic review of immunobiologic therapy for oral manifestations of pemphigoid and pemphigus
Authors: Mays Jacqueline W. , Carey Barbara P. , Posey Rachael , Gueiros Luiz Alcino , France Katherine , Setterfield Jane , Woo Sook Bin , Sollecito Thomas P. , Culton Donna , Payne Aimee S. , Greenberg Martin S. , De Rossi Scott
Published: May 2019

Objective

To assess the evidence for treatment of oral involvement of pemphigus and pemphigoid with biologics.

Study Design

This systematic review used a comprehensive search strategy to identify literature describing oral involvement of pemphigus or pemphigoid treated with a biologic agent. The primary outcome measures were efficacy and safety of biologic therapy.

Results

Inclusion criteria were met by 154 studies including over 1200 patients. Treatment of pemphigus with a total of 11 unique biologic agents and 3 unique combinations of agents is reported. Five randomized controlled trials (RCT) were included in the final analysis that investigated infliximab, IVIg, rituximab, and autologous platelet‐rich plasma therapy for pemphigus vulgaris. Three non‐RCT studies reported on successful rituximab or IVIg therapy for mucous membrane pemphigoid. Studies demonstrated considerable heterogeneity in agent, methods, and quality.

Conclusions

Evidence clearly describing oral tissue response to biologic therapy is sparse. Two RCTs support use of rituximab, one supports use of IVIg, and one pilot study suggests intralesional injection of autologous platelet‐rich plasma aids healing of oral PV lesions. As oral lesions of pemphigus and pemphigoid can be refractory to systemic therapy, drug trials including biologic therapies should document details regarding response of the oral lesions to therapy.
Comparison between epidural and opioid analgesia for infants undergoing major abdominal surgery
Authors: Martin Lizabeth D. , Adams Trevor L. , Duling Laura C. , Grigg Eliot B. , Bosenberg Adrian , Onchiri Frankline , Jimenez Nathalia
Published: May 2019

Background

Epidural analgesia is considered optimal for postoperative pain management after major abdominal surgery. The potential to decrease anesthetic and opioid exposure is particularly desirable for infants, given their vulnerability to respiratory depression and concern for anesthetic neurotoxicity. We reviewed our experience with infants undergoing major abdominal surgery to determine if epidural catheter use decreased anesthetic and opioid exposure and improved postoperative analgesia.

Methods

This retrospective cohort study included infants (<12 months) who underwent exploratory laparotomy, ureteral reimplantation, or bladder exstrophy repair between November 2011 and November 2014. Primary outcomes of anesthetic exposure (mean endtidal sevoflurane) and intraoperative opioid administration were compared between infants who received epidural catheters and those who did not. Secondary outcomes included postoperative pain and sedation scores and morphine equivalents administered 0‐24 and 24‐48 hours after surgery.

Results

Of 158 eligible infants, 82 were included and 47 received epidurals. Patients with epidurals underwent bladder exstrophy repair (N = 9), ureteral reimplantation (N = 8), and exploratory laparotomy (N = 30). Infants with epidurals received less intraoperative fentanyl (2.6 mcg/kg (0,4.5) vs 3.3 mcg/kg (2.4,5.8), P = 0.019) and morphine (6% (3/47) vs 26% (9/35), P = 0.014) in univariate analysis. After controlling for age and emergency surgery, differences in long‐acting opioid administration persisted, with significantly less morphine given in the epidural group (OR 0.181; 95% CI 0.035‐0.925; P = 0.040). Mean endtidal sevoflurane concentrations were similar between groups. There was no significant difference in postoperative median morphine equivalents.

Conclusion

Placement of epidural catheters in infants undergoing major abdominal surgery is associated with decreased long‐acting opioid requirements intraoperatively. Epidural placement does not preclude opioid exposure however, as opioids may be administered for indications other than nociceptive pain in the difficult‐to‐assess postoperative infant. Further prospective studies are warranted to better quantify the effect of epidural analgesia on intraoperative anesthetic exposure in infants.
NGS‐based targeted resequencing identified rare subtypes of albinism: Providing accurate molecular diagnosis for Japanese patients with albinism
Authors: Okamura Ken , Hayashi Masahiro , Abe Yuko , Kono Michihiro , Nakajima Kimiko , Aoyama Yumi , Nishigori Chikako , Ishimoto Hiroshi , Ishimatsu Yuji , Nakajima Mika , Hozumi Yutaka , Suzuki Tamio
Published: May 2019

Albinism, which is commonly inherited as an autosomal recessive trait, is characterized by a reduction or absence of melanin in the eyes, skin, and hair. To date, more than 20 causal genes for albinism have been identified; thus, the accurate diagnosis of albinism requires next‐generation sequencing (NGS). In this study, we analyzed 46 patients who tested negative for oculocutaneous albinism (OCA)1–4 and Hermansky‐Pudlak syndrome (HPS)1 based on conventional analysis, in addition to 28 new Japanese patients, using NGS‐based targeted resequencing. We identified a genetic background for albinism in 18 of the 46 patients (39%), who were previously tested negative according to the conventional analysis. In addition, we unveiled a genetic predisposition toward albinism in 23 of the 28 new patients (82%). We identified six patients with rare subtypes of albinism, including HPS3, HPS4, and HPS6, and found 12 novel pathological mutations in albinism‐related genes. Furthermore, most patients who were not diagnosed with albinism by the NGS analysis showed mild manifestations of albinism without apparent eye symptoms and harbored only one heterozygous mutation, occasionally in combination with skin‐color associated gene variants.
Affirmative Action: Well‐Being, Justice, and Qualifications
Authors: Segev Re’em
Published: May 2019

A common concern regarding affirmative action is that it sanctions the selection of candidates whose qualifications are not the best overall and that this is inefficient or unjust or both. I argue that this concern is misguided, since there is no independent concern regarding qualifications with respect to the moral status of affirmative action. The only sense in which qualifications are not morally arbitrary—and the only sense in which there is a reason to select the most qualified candidate—is purely instrumental to the promotion of moral values whose fundamental concern is not qualifications.
Restoration of belowground fungal communities in reclaimed landscapes of the Canadian boreal forest
Authors: Pec Gregory J. , Scott Natalie M. , Hupperts Stefan F. , Hankin Shanon L. , Landhäusser Simon M. , Karst Justine
Published: May 2019

The trajectory of forests establishing on reclaimed oil sands mines in the Canadian boreal forest is uncertain. Soil microbes, namely mycorrhizal fungi, partly underlie successional trajectories of plant communities, yet their role in restoration is often overlooked. Here, we tested the relative importance of common management tools used in restoration—species planted and soil placement—on the recovery of ectomycorrhizal fungal communities over 4 years. Importantly, we further compared the community assembly of fungi on reclaimed landscapes to that in reference ecosystems disturbed to different degrees. This latter test addresses whether disturbance intensity is more important than common management interventions to restore fungal communities in these ecosystems. Three main findings emerged. (1) The effect of tree species planted and soil placement on ectomycorrhizal fungal communities establishing on reclaimed landscapes was dynamic through time. (2) Disturbances that remove or disrupt the organic layer of soils substantially affect the composition of ectomycorrhizal fungal communities. (3) Shifts in the community composition of ectomycorrhizal fungi were driven to a greater extent by disturbance severity than either tree species planted or soil placement.
High school students’ suggestions for supporting younger pupils counteract cyberbullying
Authors: Berne Sofia , Frisén Ann , Oskarsson Josephine
Published: May 2019

This study's aim was to explore high school students’ suggestions for supporting younger pupils prevent and deal with cyberbullying. Seventy‐eight high school students participated in 11 focus groups, and had many concrete suggestions for ways they could support younger pupils against cyberbullying. The suggestions covered a range of activities, for instance advising younger pupils on how to avoid becoming victims of cyberbullying by teaching them netiquette. Furthermore, the students were positive toward involving adults in counteracting cyberbullying among younger pupils, for example educating younger pupils’ parents about cyberbullying. Moreover, the students suggested that they could show support for victims of cyberbullying by taking on the role of a friend when a younger pupil is cyberbullied and spend time with her/him during breaks. They also had ideas about supporting younger pupils in getting cyberbullies to stop, for instance by teaching the younger pupils technical skills for dealing with the cyberbullying on the Internet. To conclude, the findings in this study indicate that high school students want to be involved in supporting younger pupils against cyberbullying, and have many concrete suggestions for how this can be done. These findings have implications for counteracting cyberbullying in schools.
An international survey of maximum surgical blood ordering schedule creation and compliance
Authors: Yazer Mark H. , Kutner Jose , McCabe Julie , O'Donghaile Diarmaid , Pendergrast Jacob , Treml Angela , Wendel Silvano , Yan Matthew , Ye Zhan , Yokoyama Ana Paula , Cohn Claudia S. ,   the Biomedical Excellence for Safer Transfusion (BEST) collaborative
Published: May 2019

Background and Objectives

Maximal surgical blood order schedules (MSBOS) are prepared to assist surgeons and anaesthesiologists with pretransfusion test orders. The literature on the prevalence and usefulness of MSBOS in international settings is lacking. We developed a survey to understand the prevalence of MSBOS in hospitals and to analyse compliance with MSBOS recommendations.

Method and Materials

A survey tool was developed by the Biomedical Excellence for Safer Transfusions (BEST) collaborative. The survey link was distributed to BEST members who were encouraged to forward the link to colleagues. Survey respondents were asked to contribute data regarding their hospital's MSBOS and MSBOS compliance.

Results

There were 174 completed surveys. Greater than half of respondents did not have an MSBOS. The total number of beds was significantly different (P = 0·04) in hospitals with (N = 81) or without (N = 93) an MSBOS. Less than a quarter of respondents felt that their MSBOS was being followed despite widespread access to the MSBOS. Over 60% of type and screen orders were MSBOS compliant; however, just 42% of cross‐match orders were compliant. There was a significant difference between the number of red‐blood‐cell units returned to the blood bank when comparing MSBOS compliant and MSBOS non‐compliant cross‐match orders (227 versus 788 units, respectively, P = 0·0026).

Conclusions

An MSBOS could be a useful tool to help with pretransfusion test orders; however, the majority of respondents lacked a MSBOS. In hospitals with a MSBOS, it was reported to be under‐utilized, which might contribute to the low compliance rates seen for cross‐match orders.