bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it Getting Better or Worse? Health‐Oriented Leadership and Psychological Capital as Resources for Sustained Health in Newcomers
Authors: Arnold Miriam , Rigotti Thomas
Published: March 2020

During the transition from university to work, young adults face a stressful period in which leadership behavior serves as a guideline. Positive leadership behavior has the potential to increase internal resources, such as positive psychological capital (PsyCap). The research question addressed in this paper is if health‐oriented leadership and PsyCap as resources jointly influence the physical and mental health of novice teachers during the transition to work. In a longitudinal study, 776 novice teachers responded to three questionnaires with a time lag of 10 weeks during the first 5 months of their occupational experience. Results of a latent class growth analysis show that three trajectories of physical health and four trajectories of mental health can be distinguished. Health‐oriented leadership and PsyCap predict class membership separately, and the relationship between health‐oriented leadership and class membership is mediated by PsyCap. This implies that training supervisors in health‐oriented leadership can help novice teachers cope with stressors during their teacher training. Applying latent class growth models in this line of research is novel and adds to the understanding of internal and external resources in the process of adaptation to major life events, such as the transition from university to work.
Hunting needles in a haystack: Migrating precursors of epidermal sensory neurons in amphioxus found with serial blockface scanning electron microscopy (SBSEM)
Authors: Holland Nicholas D.
Published: March 2020

Migrating precursors of epidermal sensory neurons are a relatively rare cell type in developing amphioxus. Serial blockface scanning electron microscopy (SBSEM) was used here to locate these cells and reconstruct them in three dimensions in the context of the surrounding tissues. The reconstructions showed that, in contrast to some earlier reports, these cells are not located in an appreciable subepidermal space while they are crawling dorsally up the flank of the animal. Instead, they migrate while tightly sandwiched between overlying epidermal cells and the underlying basal lamina. The cytoplasmic region at the leading edge of the crawling cell has some characteristics of a large podosome, an F‐actin‐rich organelle with prominent roles in adhesion, matrix degradation and cell migration. The discussion includes a comparison of the precursors of epidermal sensory cells of amphioxus with migrating neurogenic cells from vertebrate placodes.
Potential strategy for assessing QT/QTc interval for drugs that produce rapid changes in heart rate: Electrocardiographic assessment of the effects of intravenous remimazolam on cardiac repolarization
Authors: Kleiman Robert B. , Darpo Borje , Thorn Michael , Stoehr Thomas , Schippers Frank
Published: March 2020

Aims

Remimazolam is a new, ultra‐short‐acting benzodiazepine developed for intravenous (IV) use during procedural sedation and in general anaesthesia. Two trials were conducted to characterize its effects on cardiac repolarization.

Methods

A thorough QT/QTc (TQT) study assessed electrocardiography effects of therapeutic and supratherapeutic doses of remimazolam and midazolam. To investigate whether RR‐QT hysteresis effects due to rapid heart rate changes might have confounded the QTc assessments in the TQT trial, a second trial used continuous IV remimazolam infusion to achieve stable heart rates during periods of stable remimazolam plasma concentration.

Results

During the TQT, both compounds produced a 10–20‐beats/min increase in heart rate within 30 seconds, persisting for 5–10 minutes. Within 30 seconds, the upper bound of the 2‐sided 90% confidence interval for the placebo‐corrected change from baseline for QTcI (ΔΔQTcI) exceeded 10 ms for both doses of remimazolam (ΔΔQTcI 7.2 [3.2, 11.2] ms for the 10 mg dose and 10.4 [6.5, 14.3] ms for the 20 mg dose) as well as for the 7.5‐mg dose of midazolam (8.2 [4.4, 12.1] ms). At 2 minutes after IV bolus, the upper bound of the 2‐sided 90% confidence interval for ΔΔQTcI exceeded 10 ms only for the remimazolam 20‐mg dose (6.3 [2.3, 10.2] ms). During the second study, during periods of stable heart rate, remimazolam had no clinically significant effect on QTc (peak ΔΔQTcI 3.4 [−1.1, 7.6] ms).

Conclusion

Remimazolam does not prolong cardiac repolarization (QTc). The methods reported here may allow assessment of the QTc effects of other drugs given by IV bolus.
Dynamic inference in general nested case‐control designs
Authors: Feifel J. , Dobler D.
Published: March 2020

Nested case‐control designs are attractive in studies with a time‐to‐event endpoint if the outcome is rare or if interest lies in evaluating expensive covariates. The appeal is that these designs restrict to small subsets of all patients at risk just prior to the observed event times. Only these small subsets need to be evaluated. Typically, the controls are selected at random and methods for time‐simultaneous inference have been proposed in the literature. However, the martingale structure behind nested case‐control designs allows for more powerful and flexible non‐standard sampling designs. We exploit that structure to find simultaneous confidence bands based on wild bootstrap resampling procedures within this general class of designs. We show in a simulation study that the intended coverage probability is obtained for confidence bands for cumulative baseline hazard functions. We apply our methods to observational data about hospital‐acquired infections.
The breaking bad effect: Priming with an antihero increases sensation seeking
Authors: Ulqinaku Aulona , Sarial‐Abi Gülen , Kinsella Elaine L. , Igou Eric R.
Published: March 2020

Antiheroes are characters that share features with both heroes and villains, typified as selfish and rule breakers, but who end up doing something good for society. In this research, we examined how priming people with antiheroes (vs. heroes) affected their sensation seeking. We reason that antiheroes (vs. heroes) are more associated with temporally close (vs. past and future) events. Given that sensation seeking is related to being focused on the present (vs. past or future), we hypothesized that if people are primed with antiheroes (vs. heroes) they are more likely to seek sensation. Findings from a series of five experimental studies provide insights into the effect of priming with an antihero on people’s sensation seeking, providing directions for future research in psychology and practical applications in the areas of marketing strategy and consumer behaviour.
MiR‐1253 exerts tumor‐suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7‐H3)
Authors: Kanchan Ranjana K. , Perumal Naveenkumar , Atri Pranita , Chirravuri Venkata Ramakanth , Thapa Ishwor , Klinkebiel David L. , Donson Andrew M. , Perry Deborah , Punsoni Michael , Talmon Geoffrey A. , Coulter Donald W. , Boue’ Daniel R. , Snuderl Matija , Nasser Mohd. W. , Batra Surinder K. , Vibhakar Rajeev , Mahapatra Sidharth
Published: March 2020

Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR‐1253, a brain‐enriched microRNA that regulates bone morphogenic proteins during cerebellar development. We hypothesized miR‐1253 confers novel tumor‐suppressive properties in medulloblastoma. Using two different cohorts of medulloblastoma samples, we first studied the expression and methylation profiles of miR‐1253. We then explored the anti‐tumorigenic properties of miR‐1253, in parallel with a biochemical analysis of apoptosis and proliferation, and isolated oncogenic targets using high‐throughput screening. Deregulation of miR‐1253 expression was noted, both in medulloblastoma clinical samples and cell lines, by epigenetic silencing via hypermethylation; specific de‐methylation of miR‐1253 not only resulted in rapid recovery of expression but also a sharp decline in tumor cell proliferation and target gene expression. Expression restoration also led to a reduction in tumor cell virulence, concomitant with activation of apoptotic pathways, cell cycle arrest and reduction of markers of proliferation. We identified two oncogenic targets of miR‐1253, CDK6 and CD276, whose silencing replicated the negative trophic effects of miR‐1253. These data reveal novel tumor‐suppressive properties for miR‐1253, i.e., (i) loss of expression via epigenetic silencing; (ii) negative trophic effects on tumor aggressiveness; and (iii) downregulation of oncogenic targets.
How ACE inhibitors transformed the renin–angiotensin system
Authors: Bakhle Y.S.
Published: March 2020

The renin–angiotensin system (RAS) now underlies the successful treatment of almost 50% of the patients in cardiovascular medicine, with serious possibilities of extension to diabetes, Alzheimer's disease and cancer. This clinical transformation started just over 50 years ago, with the unexpected identification of a bradykinin‐potentiating peptide from snake venom, as a potent inhibitor of ACE which led to the development of the first synthetic inhibitor, captopril, followed by the angiotensin receptor blockers. This article analyses the transformation of the RAS into its different stages, from academic experiments to clinical use and back to the laboratory, identifying the critical events involved, both clinical and scientific. The analysis also assesses the contributions of chance, coincidence, and conviction that were crucial in this transformation. Although questions remain, the transformation of the RAS over the past five decades provides a success story for medicine, for pharmacology, and, most significantly, for patients.
Sequential bilateral implantation in older children: Inter‐implant map differences and their effects on functional outcomes
Authors: Simões‐Franklin Cristina , Flood Isobel , Sechler Stephen , Lopez‐Valdes Alejandro , Waechter Saskia M. , Thapa Jyoti , Glynn Fergal , Walshe Peter , Reilly Richard B. , Viani Laura
Published: March 2020

Objectives

It is well established that sequential bilateral implantation offers functional benefits in speech in noise and sound localisation, although it can be challenging to get long‐term unilateral users to adapt to the second implant. The aim of this study was to investigate programming differences between the two cochlear implants that can impact on performance outcomes.

Design

Cohort Study.

Participants

Sixteen older children who received sequential implants in Ireland and with at least one‐year experience with their sequential implant were included in this study. Children were categorised into two groups according to the time interval between the two implants: short if the time between the two implants was less than eight years and long if more than eight years.

Main Outcome Measures

Dynamic ranges and current levels were compared for both implants. Functional outcome measures included sentence discrimination in quiet and in noise and sound localisation.

Results

Results show that for the children with long inter‐implant delays, the dynamic range of their second implant was on average 34% less than the dynamic range of their first implant. This difference was driven by smaller comfort levels in the second implant compared to the first. Children with longer inter‐implant delays also show lower speech discrimination scores with their second implant compared to children with shorter delays, in addition to no bilateral advantage in speech in noise, that is their performance in unilateral mode does not differ from the performance in bilateral mode. Finally, children with longer delays demonstrate poor performance in sound localisation compared to the children with shorter delays.

Conclusion

Sequentially implanted older children show limited functional benefits from the second implant. The observed functional benefits are determined both by a short inter‐implant delay and by having balanced dynamic ranges between the two implants.
Ex situ management as insurance against extinction of mammalian megafauna in an uncertain world
Authors: Farhadinia Mohammad S. , Johnson Paul J. , Zimmermann Alexandra , McGowan Philip J.K. , Meijaard Erik , Stanley‐Price Mark , Macdonald David W.
Published: March 2020

The persistence of endangered species may depend on the fate of a very small number of individual animals. In situ conservation alone may sometimes be insufficient. In these instances, the International Union for Conservation of Nature provides guidelines for ex situ conservation and the Convention on Biological Diversity (CBD) indicates how ex situ management can support the CBD's objectives by providing insurance policies for species. The circumstances that justify its use are uncertain. To evaluate the current in situ extinction risk and ex situ management of 43 critically endangered species of mammalian megafauna, we used nonmetric multidimensional scaling and geopolitical variables related to governance, economics, and national policy within their extant ranges. We then fitted generalized additive models to assess the contribution of each variable to the ordination. Fifteen (almost one‐third) of the world's terrestrial mammalian megafauna are not the subject of any ex situ management. Seventy‐three percent of these taxa occur in areas characterized by political uncertainty, such as border zones or areas affected by armed conflicts, mainly in Africa and the Middle East. A further 23% of taxa in ex situ programs do not meet sustainability criteria for inbreeding avoidance. Strategic conservation planning, such as the One Plan approach, may improve ex situ management for these taxa. Given the escalating trend in threats afflicting megafauna, ex situ management should be considered more rigorously, particularly in politically unstable regions, to achieve CBD Target 12 (prevent extinction of threatened species).
Using deep‐belief networks to understand propensity for livelihood change in a rural coastal community to further conservation
Authors: Labao Alfonso B. , Naval Prospero C. , Yap David Leonides T. , Yap Helen T.
Published: March 2020

Overharvesting of terrestrial and marine resources may be alleviated by encouraging an alternative configuration of livelihoods, particularly in rural communities in developing countries. Typical occupations in such areas include fishing and farming, and rural households often switch livelihood activities to suit climate and economic conditions. We used a machine‐learning tool, deep‐belief networks (DBN), and data from surveys of a rural Philippine coastal community to examine household desire to change livelihood. This desire is affected by a variety of factors, such as income, family needs, and feelings of work satisfaction, that are interrelated in complex ways. In farming households, livelihood changes often occur to diversify resources, increase income, and lessen economic risk. The DBN, given its multilayer perceptron structure, has a capacity to model nonlinear relationships among factors while providing an acceptable degree of accuracy. Relative to a set of 34 features (e.g., education, boat ownership, and work satisfaction), we examined the binary response variables desire to change work or not to change work. The best network had a test set accuracy of 97.5%. Among the features, 7 significantly affected desire to shift work: ethnicity, work satisfaction, number of persons in a household in ill health, number of fighting cocks owned, fishing engagement, buy‐and‐sell revenue, and educational level. A cross‐correlation matrix of these 7 features indicated households less inclined to change work were those engaged in fishing and retail buying and selling. For fishing, provision of economic and other incentives should be considered to encourage changing from this occupation to allow recovery of fishery resources.
Math anxiety and math achievement: The effects of emotional and math strategy training
Authors: Passolunghi Maria Chiara , De Vita Chiara , Pellizzoni Sandra
Published: March 2020

Math anxiety (MA) is a specific feeling of tension generated by the manipulation of numerical stimuli in daily life and academic situations (Richardson & Suinn, 1972). This condition has significant repercussions on the individual's life at personal, social, and economic level. Literature on the topic of MA alleviation, however, is still scarce. This study aims at contributing to this field by addressing MA prevention in school‐age children. We have developed two different training methods administered to two groups of fourth graders: (a) MA training focusing on identifying and copying with MA‐related feelings (N = 76); and (b) Math strategy training focusing on supplementary exercises to enhance calculation strategies (N = 76). We also carried out a Control training involving a range of activities, such as reading comic strips, describing characters in the story, and combining text and images to obtain an original narrative text (N = 72). We evaluated the differential effects of these training methods on MA, general anxiety, and math achievement before and after the training. Results indicate that MA training contributes to a decrease in MA level, although it does not appear to affect math achievement; Math strategy training, on the other hand, results in far transfer on a reduction of MA level as well as near transfer on the improvement of math achievement. Data are discussed in terms of specific mechanisms underlying each type of training method, and with specific focus on the evaluation of educational and developmental opportunities linked to MA prevention and improvement of math abilities in school‐age children.
Fostering research pathways to positive long‐term outcomes for childhood‐onset epilepsy
Authors: Speechley Kathy Nixon
Published: March 2020

This commentary is on the original article by Kesselmayer et al. on pages 587–592 of this issue.
The ‘brick diet’ and postprandial insulin: a practical method to balance carbohydrates ingested and prandial insulin to prevent hypoglycaemia in hospitalized persons with diabetes
Authors: Avanzini F. , Marelli G. , Amodeo R. , Chiappa L. , Colombo E. L. , Di Rocco E. , Grioni M. , Moro C. , Roncaglioni M. C. , Saltafossi D. , Vandoni P. , Vannini T. , Vilei V. , Riva E. ,   the Desio Diabetes Diagram (DDD) Study Group
Published: March 2020

Aim

Insulin is the preferred treatment for the control of diabetes in hospital, but it raises the risk of hypoglycaemia, often because oral intake of carbohydrates in hospitalized persons is lower than planned. Our aim was to assess the effect on the incidence of hypoglycaemia of giving prandial insulin immediately after a meal depending on the amount of carbohydrate ingested.

Methods

A prospective pre–post intervention study in hospitalized persons with diabetes eating meals with stable doses of carbohydrates present in a few fixed foods. Foods were easily identifiable on the tray and contained fixed doses of carbohydrates that were easily quantifiable by nurses as multiples of 10 g (a ‘brick’). Prandial insulin was given immediately after meals in proportion to the amount of carbohydrates eaten.

Results

In 83 of the first 100 people treated with the ‘brick diet’, the oral carbohydrate intake was lower than planned on at least one occasion (median: 3 times; Q1–Q3: 2–6 times) over a median of 5 days. Compared with the last 100 people treated with standard procedures, postprandial insulin given on the basis of ingested carbohydrate significantly reduced the incidence of hypoglycaemic events per day, from 0.11 ± 0.03 to 0.04 ± 0.02 (P < 0.001) with an adjusted incidence rate ratio of 0.70 (95% confidence interval 0.54–0.92; P = 0.011).

Conclusions

In hospitalized persons with diabetes treated with subcutaneous insulin, the ‘brick diet’ offers a practical method to count the amount of carbohydrates ingested, which is often less than planned. Prandial insulin given immediately after a meal, in doses balanced with actual carbohydrate intake reduces the risk of hypoglycaemia.
Understanding dental students’ use of feedback
Authors: Freeman Zoe , Cairns Alison , Binnie Viv , McAndrew Robery , Ellis Janice
Published: March 2020

Introduction

Feedback can enhance learning and is thought to be highly valued by students; however, it is not clear from the literature how dental students actually use feedback.

Aim

This study aimed to explore how dental students use feedback in a variety of contexts.

Methods

Qualitative methods involving audio‐recorded focus groups were used to explore the use of feedback by undergraduate dental students studying at three UK dental schools. A purposive sampling strategy was used to ensure diverse representation across the undergraduate dental programmes in each of the schools.

Results

Six focus groups, involving a total of 72 students, were undertaken. Thematic analysis identified five main themes relating to the use of feedback: value, future applicability, accessibility, variability and understanding. The inter‐connectivity and interaction of the themes (along with their subthemes) were used to develop a model for optimising feedback with the aim of enhancing its potential use by students.

Conclusion

The use of feedback by students would appear to be strongly influenced by several factors. Understanding these factors and how they interlink may be helpful to education providers who are seeking to optimise their feedback processes.
c‐MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide‐dexamethasone in myeloma
Authors: Di Bacco Alessandra , Bahlis Nizar J. , Munshi Nikhil C. , Avet‐Loiseau Hervé , Masszi Tamás , Viterbo Luísa , Pour Ludek , Ganly Peter , Cavo Michele , Langer Christian , Kumar Shaji K. , Rajkumar S. Vincent , Keats Jonathan J. , Berg Deborah , Lin Jianchang , Li Bin , Badola Sunita , Shen Lei , Zhang Jacob , Esseltine Dixie‐Lee , Luptakova Katarina , van de Velde Helgi , Richardson Paul G. , Moreau Philippe
Published: March 2020

Objectives

In the TOURMALINE‐MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib‐lenalidomide‐dexamethasone (IRd) showed different magnitudes of progression‐free survival (PFS) benefit vs placebo‐Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT).

Methods

RNA sequencing data were used to investigate the basis of these differences.

Results

The PFS benefit of IRd vs placebo‐Rd was greater in patients with tumors expressing high c‐MYC levels (median not reached vs 11.3 months; hazard ratio [HR] 0.42; 95% CI, 0.26, 0.66; P < .001) compared with in those expressing low c‐MYC levels (median 20.6 vs 16.6 months; HR 0.75; 95% CI, 0.42, 1.2). Expression of c‐MYC in tumors varied based on the number and type of prior therapy received, with the lowest levels observed in tumors of patients who had received 1 prior line of therapy including SCT. These tumors also had higher expression levels of CD19 and CD81.

Conclusions

PFS analyses suggest that lenalidomide and ixazomib target tumors with different levels of c‐MYC, CD19, and CD81 expression, thus providing a potential rationale for the differential benefits observed in the TOURMALINE‐MM1 study. This trial was registered at www.clinicaltrials.gov as: NCT01564537
MEC (mitoxantrone, etoposide, and cytarabine) induces complete remission and is an effective bridge to transplant in acute myeloid leukemia
Authors: Marconi Giovanni , Talami Annalisa , Abbenante Maria Chiara , Sartor Chiara , Parisi Sarah , Nanni Jacopo , Bertamini Luca , Ragaini Simone , Olivi Matteo , de Polo Stefano , Cristiano Gianluca , Fontana Maria Chiara , Bochicchio Maria Teresa , Ottaviani Emanuela , Arpinati Mario , Sessa Mariarosaria , Baldazzi Carmen , Caso Lucia , Testoni Nicoletta , Baccarani Michele , Bonifazi Francesca , Martinelli Giovanni , Paolini Stefania , Cavo Michele , Papayannidis Cristina , Curti Antonio
Published: March 2020

Introduction

Clinical response and chemosensitivity of relapse or refractory AML patients were evaluated after rescue and bridge‐to‐transplant MEC (mitoxantrone, etoposide, and cytarabine) regimen.

Methods and Patients

Fifty‐five consecutive AML patients were treated with MEC from 2009 to 2018. Chemosensitivity was evaluated by WT1 quantification.

Results

27/55 patients (49.1%) had AML resistant to induction and 28/55 patients (50.9%) had AML relapse. 25/55 patients (45.5%) achieved a CR after one course of MEC, and 12 patients (21.8%) achieved WT1 negativity. In 12 patients, a second MEC was administered. Four out of 12 patients improved significantly their response with the 2nd MEC. MEC was an effective bridge to transplant, 32/55 patients (58.2%) received an allogenic stem cell transplant. Median overall survival (OS) from MEC was 455 days (95% CI 307‐602 days.); patient with WT1 negative CR had the best OS (P<.000).

Conclusion

WT1 is a useful marker of chemosensitivity after MEC as rescue and bridge‐to‐transplant therapy.
The multi‐tyrosine kinase inhibitor ponatinib for chronic myeloid leukemia: Real‐world data
Authors: Luciano Luigia , Annunziata Mario , Attolico Immacolata , Di Raimondo Francesco , Maggi Alessandro , Malato Alessandra , Martino Bruno , Palmieri Fausto , Pane Fabrizio , Sgherza Nicola , Specchia Giorgina
Published: March 2020

Development of the highly selective targeted tyrosine kinase inhibitors (TKIs) has expanded the therapeutic options for chronic myeloid leukemia (CML). Patients undergoing TKI therapy should be closely monitored to ensure that the best therapeutic response and quality of life are achieved, and to control suboptimal responses and adverse events. Despite the high rate of response using current first‐line TKIs, treatment failure may still occur, and resistance is considered a challenge in the treatment of patients with CML. The third‐generation TKI, ponatinib, is a potent orally bioavailable pan BCR‐ABL inhibitor that inhibits both wild‐type and mutant BCR‐ABL1 kinase, including the “gatekeeper” T315I mutation, which is resistant to all other currently available TKIs. This paper reviews the effectiveness, feasibility, and safety of ponatinib in the real‐life clinical management of CML. Potential prognostic factors in identifying patients most likely to benefit from ponatinib treatment will be discussed, and case presentations illustrating situations encountered in real‐life clinical practice are described. Ponatinib is effective in patients who have received prior TKIs in clinical studies as well as under real‐life conditions. Nevertheless, the risk/benefit balance must be evaluated for each patient, particularly considering disease state, mutational status, treatment line, intolerance/resistance to prior TKIs, age, frailty, and specific comorbidities.
Population‐level multiplexing: A promising strategy to manage the evolution of resistance against gene drives targeting a neutral locus
Authors: Edgington Matthew P. , Harvey‐Samuel Tim , Alphey Luke
Published: March 2020

CRISPR‐based gene drives bias inheritance in their favour by inducing double‐stranded breaks (DSBs) at wild‐type homologous loci and using the drive transgene as a repair template—converting drive heterozygotes into homozygotes. Recent studies have shown that alternate end‐joining repair mechanisms produce cut‐resistant alleles that rapidly induce drive failure. Multiplexing—simultaneously targeting multiple sites at the wild‐type locus—is commonly assumed to overcome this issue since resistance would need to develop at all target sites for the system to fail. This may work for some population suppression drives targeting essential (e.g. viability or fertility) genes if careful design can ensure cut‐resistant alleles themselves have low fitness. However, here, models are used to demonstrate that this approach will be ineffective when targeting neutral loci. We then go on to compare the performance of four alternative population‐level multiplexing approaches with standard individual‐level multiplexing. Two of these approaches have mechanisms preventing them from becoming linked, thus avoiding multiple simultaneous DSBs and giving a large improvement. Releasing multiple unlinked drives gives a modest improvement, while releasing multiple drives that may become linked over time produces a decrease in performance under the conditions tested here. Based on performance and technical feasibility, we then take one approach forward for further investigation, demonstrating its robustness to different performance parameters and its potential for controlling very large target populations.
A long‐term study of equine cheek teeth post‐extraction complications: 428 cheek teeth (2004‐2018)
Authors: Kennedy Rebekah , Reardon Richard J. M. , James Oliver , Wilson Cherith , Dixon Padraic M.
Published: March 2020

Background

Complications, especially delayed alveolar healing, are common following equine cheek teeth extraction, however, limited objective information is available on the prevalence and nature of these problems.

Objectives

To document the type and prevalence of complications that occur following equine cheek tooth extraction and to identify possible risk factors for these complications that could be used to predict their occurrence and hopefully reduce their prevalence.

Study design

Retrospective cohort study.

Methods

Clinical records of all cheek teeth extractions performed between February 2004 and September 2018 were examined and written questionnaires sent to owners. Details of post‐extraction complications were analysed and logistic regression was used to evaluate potential associations between the likelihood of post‐extraction nonhealing alveolus managed by the authors and the variables: age, breed, reason for extraction, Triadan position and extraction technique.

Results

Post‐extraction complications were recorded following 58/428 extractions giving an overall complication rate of 13.6%, that caused a longer term clinical problem in 34/428 (7.9%) cases, with complications being asymptomatic or quickly self‐resolving in the other 24 cases (5.6%). The most frequent complication was alveolar bone sequestration, including alveolar infection. Risk of developing a post‐extraction alveolar disorder managed by the authors (n = 53) increased following extraction of the mandibular 06s, 07s or 08s compared with all other cheek teeth combined (P = .001); for cheek teeth with apical infections (P = .002) compared with those without; and following repulsion or minimally invasive transbuccal extraction (MTE) than following oral extraction (P = .01 and P = .02 respectively).

Main limitations

Length of time between exodontia and survey data collection for some cases, use of clinical records and survey data and biases associated with decision to treat.

Conclusions

In agreement with previous studies, oral extraction had the lowest risk of complications. This study provides new information regarding the prevalence, types and risk of development of post extraction complications. Knowledge of these risk factors may help reduce these complications.
Development of the blood supply to the growth cartilage of the medial femoral condyle of foals
Authors: Wormstrand Bjørn H. , Fjordbakk Cathrine T. , Griffiths David J. , Lykkjen Sigrid , Olstad Kristin
Published: March 2020

Background

Growth cartilage is found in the articular‐epiphyseal cartilage complex (AECC) and the physis. It has a temporary blood supply organised as end arteries. Vascular failure is associated with osteochondrosis, but infection can also obstruct vessels. The location of bacteria was recently compared to arterial perfusion, and the results indicated that they were located in the distal tips of AECC end arteries. Systematic perfusion studies were not available for comparison to the infected physes. Further studies may improve our understanding of infections and other pathologies.

Objectives

To describe development of the blood supply to the growth cartilage of the medial femoral condyle in fetuses and foals from 228 days of gestation to 62 days old.

Study design

Ex vivo arterial perfusion study.

Methods

The left medial femoral condyle of 10 Norwegian Fjord Pony fetuses and foals (228 days of gestation to 62 days old) and one Norwegian‐Swedish Coldblooded Trotter foal (10 days old) was arterially perfused with barium and underwent micro‐computed tomography, qualitative and quantitative description of vessels.

Results

In the fetus, the physis was supplied by metaphyseal‐origin arteries. In 1‐10 day‐old foals, the physis was supplied by a mixture of metaphyseal‐ and epiphyseal‐origin arteries, and from 15 days of age by epiphyseal‐origin arteries only. The number of vessels increased before it decreased in both the AECC and the physis postnatally. Vessels in the cartilage showed a monopodial branching pattern, whereas vessels in epiphyseal and metaphyseal bone showed both monopodial and dichotomous branching.

Main limitations

Foals with confirmed pathologies were not examined.

Conclusions

The blood supply to growth cartilage changed with age, including the physeal supply that changed from metaphyseal‐ to epiphyseal‐origin arteries. The number of vessels increased before it decreased postnatally, and two different branching patterns were observed. These results may improve our understanding of growth cartilage vascular failure and osteomyelitis.
Fibroblast‐specific genome‐scale modelling predicts an imbalance in amino acid metabolism in Refsum disease
Authors: Wegrzyn Agnieszka B. , Herzog Katharina , Gerding Albert , Kwiatkowski Marcel , Wolters Justina C. , Dolga Amalia M. , van Lint Alida E. M. , Wanders Ronald J. A. , Waterham Hans R. , Bakker Barbara M.
Published: March 2020

Refsum disease (RD) is an inborn error of metabolism that is characterised by a defect in peroxisomal α‐oxidation of the branched‐chain fatty acid phytanic acid. The disorder presents with late‐onset progressive retinitis pigmentosa and polyneuropathy and can be diagnosed biochemically by elevated levels of phytanate in plasma and tissues of patients. To date, no cure exists for RD, but phytanate levels in patients can be reduced by plasmapheresis and a strict diet. In this study, we reconstructed a fibroblast‐specific genome‐scale model based on the recently published, FAD‐curated model, based on Recon3D reconstruction. We used transcriptomics (available via GEO database with identifier GSE138379), metabolomics and proteomics (available via ProteomeXchange with identifier PXD015518) data, which we obtained from healthy controls and RD patient fibroblasts incubated with phytol, a precursor of phytanic acid. Our model correctly represents the metabolism of phytanate and displays fibroblast‐specific metabolic functions. Using this model, we investigated the metabolic phenotype of RD at the genome scale, and we studied the effect of phytanate on cell metabolism. We identified 53 metabolites that were predicted to discriminate between healthy and RD patients, several of which with a link to amino acid metabolism. Ultimately, these insights in metabolic changes may provide leads for pathophysiology and therapy.

Databases

Transcriptomics data are available via GEO database with identifier GSE138379, and proteomics data are available via ProteomeXchange with identifier PXD015518.
The microstructure, mechanical, and fatigue behaviours of MAG welded G20Mn5 cast steel
Authors: Wu S.C. , Qin Q.B. , Hu Y.N. , Branco R. , Li C.H. , Williams C.J. , Zhang W.H.
Published: March 2020

The microstructure, mechanical strength, and fatigue response of metal active gas (MAG) butt‐welded G20Mn5 cast steel was thoroughly investigated for exploring the service safety and reliability of new‐generation railway bogie frames. The fatigue properties of the matrix and welded joints were determined by both low‐ and high‐cycle service regimes. On the basis of nanoindentation testing, the fatigue crack growth (FCG) was derived by correlating with cyclic plastic response of microdomain materials across the MAG joint. The results show that the MAG induces considerable changes in microstructures and hardness of the G20Mn5 matrix and resultantly produces an overmatching welded joint but show comparatively low‐ and high‐cycle fatigue properties to as‐received material. The calculated threshold FCG range based on the Murakami model indicates that the maximum 1.5‐mm defect might be the cracking site subjected to fatigue loading from the structural integrity viewpoint.
Reforestation and surface cooling in temperate zones: Mechanisms and implications
Authors: Zhang Quan , Barnes Mallory , Benson Michael , Burakowski Elizabeth , Oishi A. Christopher , Ouimette Andrew , Sanders‐DeMott Rebecca , Stoy Paul C. , Wenzel Matt , Xiong Lihua , Yi Koong , Novick Kimberly A.
Published: March 2020

Land‐use/cover change (LUCC) is an important driver of environmental change, occurring at the same time as, and often interacting with, global climate change. Reforestation and deforestation have been critical aspects of LUCC over the past two centuries and are widely studied for their potential to perturb the global carbon cycle. More recently, there has been keen interest in understanding the extent to which reforestation affects terrestrial energy cycling and thus surface temperature directly by altering surface physical properties (e.g., albedo and emissivity) and land–atmosphere energy exchange. The impacts of reforestation on land surface temperature and their mechanisms are relatively well understood in tropical and boreal climates, but the effects of reforestation on warming and/or cooling in temperate zones are less certain. This study is designed to elucidate the biophysical mechanisms that link land cover and surface temperature in temperate ecosystems. To achieve this goal, we used data from six paired eddy‐covariance towers over co‐located forests and grasslands in the temperate eastern United States, where radiation components, latent and sensible heat fluxes, and meteorological conditions were measured. The results show that, at the annual time scale, the surface of the forests is 1–2°C cooler than grasslands, indicating a substantial cooling effect of reforestation. The enhanced latent and sensible heat fluxes of forests have an average cooling effect of −2.5°C, which offsets the net warming effect (+1.5°C) of albedo warming (+2.3°C) and emissivity cooling effect (−0.8°C) associated with surface properties. Additional daytime cooling over forests is driven by local feedbacks to incoming radiation. We further show that the forest cooling effect is most pronounced when land surface temperature is higher, often exceeding −5°C. Our results contribute important observational evidence that reforestation in the temperate zone offers opportunities for local climate mitigation and adaptation.
Hierarchical global plant biophysical regions as potential analysis units
Authors: Boone Randall B.
Published: March 2020

Regional and global vegetation simulations can be problematic when analysis units to which parameters are assigned do not align with plant productivity and phenology. Having a suite of predefined biophysical regions at a variety of scales that correspond to differences in plant productivity and phenology would allow analysts to select a set of analysis units at the scale needed. In other cases, environmental or social responses may be hypothesized to be related to differences in plant dynamics. One may compare the discrimination in such data that biophysical regions at different scales provide to determine which best distinguishes the responses in question, such that like responses fall within the same regions to the degree possible. If those relationships are significant, the responses may then be extrapolated based on the biophysical regions. I defined hierarchical biophysical regions based on plant productivity and phenology by clustering global 0.083 degree resolution normalized difference vegetation indices (NDVI) over a 10 year period. Agglomerative average‐linkage distances based on squared error between clusters were conducted using an iterative sampling approach to merge more than 2 million clusters into fewer and fewer clusters based on NDVI greenness profiles comprised of 240 values over 10 years, until all cells were in a single cluster. Greater and greater differences in greenness profiles were ignored at higher levels of the hierarchy. Using a difference increment of 0.1, 253 non‐duplicative sets of clusters were created, and 107 of those were included in animations that may be used to explore differences in global plant dynamics. Differences in clusters were quantified based on comparing the focal set of cluster results with 10 other cluster sets. Analysts may use the hierarchical clusters to improve the alignment of their parameter sets that inform plant growth and other dynamics with real‐world plant dynamics.
Null models for community dynamics: Beware of the cyclic shift algorithm
Authors: Kalyuzhny Michael
Published: March 2020

Aim

Temporal patterns of community dynamics are drawing increasing interest due to their potential to shed light on assembly processes and anthropogenic effects. However, interpreting such patterns considerably benefits from comparing observed dynamics to the reference of a null model. For that aim, the cyclic shift permutations algorithm, which generates randomized null communities based on empirically observed time series, has recently been proposed. This algorithm, borrowed from the spatial analysis literature, shifts each species time series randomly in time, and this is claimed to preserve the temporal autocorrelation of single species. Hence it has been used to test the significance of various community patterns, in particular excessive compositional changes, biodiversity trends and community stability.

Innovation

Here I critically study the properties of the cyclic shift algorithm for the first time. I show that, unlike previously suggested, this algorithm does not preserve temporal autocorrelation due to the need to ‘wrap’ the time series and assign the last observations to the first years. Moreover, this algorithm scrambles the initial state of the community, making any dynamics that result from deviations from equilibrium seem excessive. I exemplify that these two issues lead to a highly elevated type I error rate in tests for excessive compositional changes and richness trends.

Conclusions

Caution is needed when using the cyclic shift permutation algorithm and interpreting results obtained using it. Interpretation is further complicated because the algorithm removes all correlations between species. I suggest guidelines for using this method and discuss several possible alternative approaches. The non‐preservation of autocorrelation also raises questions regarding the use of the analogous spatial null model, the torus‐translation.
Improving patient engagement by fostering the sharing of activity tracker data with providers: a qualitative study
Authors: Shin Grace Donghee , Feng Yuanyuan , Gafinowitz Nicci , Jarrahi Mohammad Hossein
Published: March 2020

Background

Activity trackers are becoming increasingly popular, but patients often hesitate to share the data from such devices with their health care providers. Researchers have shown that sharing everyday health data with physicians can foster greater patient engagement.

Objectives

This research is intended to investigate activity tracker users’ decisions regarding the sharing of their activity tracker data with physicians, as well as to build a stage based framework for improving patient engagement by fostering such data sharing.

Methods

Qualitative analysis of interview records of 12 adults, who had used Fitbit activity tracking devices for up to two years, identifying emotions and experiences surrounding their tendencies to share physical exercise data with a physician.

Results

This research used the subjects’ emotions and considerations regarding the decision over whether to share exercise data with physicians to create a stage based framework with three stages: cognisance, tangible evidence and supportive feedback.

Conclusion

The tendency to progress towards three stages with greater patient–physician engagement appears to increase with health risk profile and with reduced data privacy concerns. This framework contributes to ongoing discussions about establishing patient–practitioner engagement, based around patients’ shared personal data collection.
The important role of the histopathologist in clinical trials: challenges and approaches to tackle them
Authors: Provenzano Elena , Driskell Owen J , O'Connor Daniel J , Rodriguez‐Justo Manuel , McDermott Jacqueline , Wong Newton , Kendall Timothy , Zhang Yu Zhi , Robinson Max , Kurian Kathreena M , Pell Robert , Shaaban Abeer M
Published: March 2020

High‐quality histopathology is essential for the success of clinical trials. Histopathologists have a detailed understanding of tumour biology and mechanisms of disease, as well as practical knowledge of optimal tissue handling and logistical service requirements for study delivery, such as biomarker evaluation, tissue acquisition and turnaround times. As such, histopathologist input is essential throughout every stage of research and clinical trials, from concept development and study design to trial delivery, analysis and dissemination of results. Patient recruitment to trials takes place among all healthcare settings, meaning that histopathologists make an invaluable contribution to clinical trials as part of their routine day‐to‐day work that often goes unrecognised. More complex evaluation of surgical specimens in the neoadjuvant setting and ever‐expanding minimum data sets add to the workload of every histopathologist, not just academic pathologists in tertiary centres. This is occurring against a backdrop of increasing workload pressures and a worldwide shortage of histopathologists and biomedical scientists. Providing essential histopathology support for trials at grassroots level requires funding for adequate resources including histopathologist time, education and training, biomedical scientist and administrative support and greater recognition of the contribution made by histopathology. This paper will discuss the many ways in which histopathologists are involved in clinical trials and the challenges faced in meeting the additional demands posed by trial participation and potential ways to address this, with a special emphasis on the UK model and the Cellular–Molecular Pathology Initiative (CM‐Path).