bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmed mechano-chemical coupling in reaction-diffusion active matter
Authors: Senoussi Anis , Galas Jean-Christophe , Estevez-Torres André
Published: March 2021

Embryo morphogenesis involves a complex combination of pattern-forming mechanisms. However, classicalin vitropatterning experiments explore only one mechanism at a time, thus missing coupling effects. Here, we conjugate two major pattern-forming mechanisms —reaction-diffusion and active matter— by integrating dissipative DNA/enzyme reaction networks within an active gel composed of cytoskeletal motors and filaments. We show that the strength of the flow generated by the active gel controls the mechano-chemical coupling between the two subsystems. This property was used to engineer a synthetic material where contractions trigger chemical reaction networks both in time and space, thus mimicking key aspects of the polarization mechanism observed inC. elegansoocytes. We anticipate that reaction-diffusion active matter will promote the investigation of mechano-chemical transduction and the design of new materials with life-like properties.
Temporally distinct oscillatory codes of retention and manipulation of verbal working memory
Authors: Pavlov Yuri G. , Kotchoubey Boris
Published: March 2021

Most psychophysiological studies of working memory (WM) target only the short-term memory construct, while short-term memory is only a part of the WM responsible for the storage of sensory information. Here, we aimed to further investigate oscillatory brain mechanisms supporting the executive components of WM – the part responsible for the manipulation of information. We conducted an exploratory reanalysis of a previously published EEG dataset where 156 participants (82 females) performed tasks requiring either simple retention or retention and manipulation of verbal information in WM. A relatively long delay period (>6s) was employed to investigate the temporal trajectory of the oscillatory brain activity. Compared to baseline, theta activity was significantly enhanced during encoding and the delay period. Alpha-band power decreased during encoding and switched to an increase in the first part of the delay before returning to the baseline in the second part; beta-band power remained below baseline during encoding and the delay. The difference between the manipulation and retention tasks in spectral power had diverse temporal trajectories in different frequency bands. The difference maintained over encoding and the first part of the delay in theta, during the first part of the delay in beta, and during the whole delay period in alpha. Our results suggest that task-related modulations in theta power co-vary with the demands on the executive control network; beta suppression during mental manipulation can be related to the activation of motor networks; alpha is likely to reflect the activation of language areas simultaneously with sensory input blockade.
Transitioning to online learning during the COVID-19 pandemic: differences in access and participation among students in disadvantaged school districts
Authors: Catalano Amy J. , Torff Bruce , Anderson Kevin S.
Published: March 2021

Purpose

The novel coronavirus, COVID-19, which emerged in 2019 and quickly spread to the United States, resulted in widespread closure of PreK-12 schools and universities and a rapid transition to online learning. There are concerns about how students in high-needs school districts will engage with online learning, given the limited access many disadvantaged students have to Internet and computers. Accordingly, the purpose of this study is to determine teacher perceptions of students' access and participation to online learning, as well as concerns about educational outcomes among different groups of learners.

Design/methodology/approach

The authors surveyed 300 K-12 teachers in NY state about the tools and accommodations they employed in their online teaching, whether their students were participating in the online learning and the reasons for their lack of participation.

Findings

Respondents reported that nearly 30% of all of their students were not regularly completing their assignments. Students in high-needs districts were significantly more likely to not complete their work. Teachers reported being very concerned about their students' educational outcomes, particularly students with disabilities (SWDs) and English language learners (ELLs). Respondents also provided suggestions for improving educational access to online learning in the future.

Originality/value

No published research has yet examined student compliance in online learning during an emergency and, in particular, during this unprecedented time of the COVID-19 pandemic and months-long stay-at-home orders.
An improved imperfect maintenance strategy for multiperiod randomly failing equipment with stochastic repair times
Authors: Dellagi Sofiene , Darghouth Mohamed Noomane
Published: March 2021

Purpose

In this paper, a maintenance strategy based on improved imperfect maintenance actions with stochastic repair times for multiperiod randomly failing equipment is developed. The main objective is to minimize the total maintenance cost by jointly finding the optimal preventive maintenance (PM) cycle and planning horizon.

Design/methodology/approach

A model based on the mathematical theory of reliability is developed to minimize the total maintenance cost by jointly finding the optimal couple: PM cycle T* and planning horizon H*. The proposed model aims to characterize the evolutionary impact of imperfect PM actions on the equipment failure rate and the resulting mean number of failures. The conventional threshold accepting (TA) algorithm is implemented to solve the proposed model. A numerical example for a given set of input parameters is presented in order to show the usefulness of the proposed model. A sensitivity analysis of some of the key parameters is performed to demonstrate the coherence of the developed maintenance policy.

Findings

The obtained results showed a sensitive trade-off between PM frequency and the total maintenance cost. Performing PM actions more frequently helps significantly to reduce the expected number of corrective maintenance actions and the corresponding total cost. It has also been found that improving the efficiency of the PM actions allows for maintaining the equipment less frequently by increasing the time between successive PM actions.

Research limitations/implications

Given the complexity of the objective function to be minimized and the stochastic nature of the model's parameters, the authors limited this study to equally cyclic production periods over the planning horizon.

Practical implications

The present model aims to provide an integrated maintenance/production comprehensive framework to assist planners in establishing maintenance schedules considering multiperiod randomly failing production systems and the evolutionary impact of imperfect PM actions on the equipment failure rate.

Originality/value

Contrary to the majority of existing works in the literature dealing with maintenance strategies, the authors consider that repair times are stochastic to provide a more realistic framework. In addition, the developed model considers the impact of imperfect maintenance on the equipment's mean time to failure. Thus, the evolutionary impact of imperfect PM actions on the equipment failure rate and the resulting mean number of failures is characterized. Simultaneously, the production planning horizon along with the length of each PM cycle is optimized in order to minimize the total maintenance cost over the planning horizon.
Five‐year survival with nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma
Authors: Uhara Hisashi , Kiyohara Yoshio , Uehara Jiro , Fujisawa Yasuhiro , Takenouchi Tatsuya , Otsuka Masaki , Uchi Hiroshi , Fukushima Satoshi , Minami Hironobu , Hatsumichi Masahiro , Yamazaki Naoya
Published: March 2021

We report the 5‐year follow‐up results from a single‐arm, open‐label, multicenter phase II study (ONO‐4538‐08) conducted in Japan. Twenty‐four patients with treatment‐naïve, recurrent, or unresectable stage III/IV malignant melanoma received 3 mg/kg nivolumab every 2 weeks until progressive disease or unacceptable toxicity occurred. The 5‐year overall survival (OS) rate was 26.1%. Five years after the start of nivolumab treatment, there were six survivors. The 5‐year OS rate was 66.7% for patients with a superficial spreading type, 14.3% for acral lentiginous type, and 16.7% for mucosal type. The 5‐year progression‐free survival rate was 17.2%. No new cases of partial response or complete response were observed after 3 years, and overall response and disease control rates were similar to those reported at 3 years. The treatment‐related adverse events reported between the 3‐ and 5‐year follow‐up periods were anemia (grade 2), white blood cell count decrease (grade 2), and psoriasiform dermatitis (grade 2) in one patient each. No new grade 3 or higher treatment‐related adverse events occurred in this period. In conclusion, first‐line treatment with nivolumab in Japanese patients with unresectable or metastatic melanoma resulted in confirmed long‐term survival. No new safety signals were reported in the studied population.
Early warning indicators of population collapse in a seasonal environment
Authors: Burant Joseph B. , Park Candace , Betini Gustavo S. , Norris D. Ryan
Published: March 2021

Recent studies have demonstrated that generic statistical signals derived from time series of population abundance and fitness‐related traits of individuals can provide reliable indicators of impending shifts in population dynamics. However, how the seasonal timing of environmental stressors influences these early warning indicators is not well understood.

The goal of this study was to experimentally assess whether the timing of stressors influences the production, detection and sensitivity of abundance‐ and trait‐based early warning indicators derived from declining populations.

In a multi‐generation, season‐specific habitat loss experiment, we exposed replicate populations of Drosophila melanogaster to one of two rates of chronic habitat loss (10% or 20% per generation) in either the breeding or the non‐breeding period. We counted population abundance at the beginning of each season, and measured body mass and activity levels in a sample of individuals at the end of each generation.

When habitat was lost during the breeding period, declining populations produced signals consistent with those documented in previous studies. Inclusion of trait‐based indicators generally improved the detection of impending population collapse. However, when habitat was lost during the non‐breeding period, the predictive capacity of these indicators was comparatively diminished.

Our results have important implications for interpreting signals in the wild because they suggest that the production and detection of early warning indicators depends on the season in which stressors occur, and that this is likely related to the capacity of populations to respond numerically the following season.
Early and systematic administration of fibrinogen concentrate in postpartum haemorrhage following vaginal delivery: the FIDEL randomised controlled trial
Authors: Ducloy‐Bouthors AS , Mercier FJ , Grouin JM , Bayoumeu F , Corouge J , Le Gouez A , Rackelboom T , Broisin F , Vial F , Luzi A , Capronnier O , Huissoud C , Mignon A ,   the FIDEL working group
Published: March 2021

Objective

To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management.

Design

Multicentre, double‐blind, randomised placebo‐controlled trial. Setting: 30 French hospitals.

Population

Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins.

Methods

Within 30 minutes after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo.

Main outcome measures

Failure as composite primary efficacy endpoint: at least 4 g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48 hours following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures and maternal morbidity–mortality within 6 ± 2 weeks after delivery.

Results

437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346 ml) and plasma fibrinogen (4.1 ± 0.9 g/l) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR] = 0.99) after adjustment for centre and baseline plasma fibrinogen; (95% CI 0.66–1.47; P = 0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group.

Conclusions

As previous placebo‐controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events.

Tweetable abstract

Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.
Utility of non‐contrast head computed tomography in poisoned patients
Authors: McNulty Richard , Bandaranayake Lashnika , Wong Timothy , Garner Alex , Tahmid Farhan , Symes Emily , Mohammad Mohammad , Salter Mark , Gunja Naren
Published: March 2021

Objective

To investigate the utility of non‐contrast head computed tomography (CT) in poisoned patients.

Methods

A retrospective cohort study of patients referred to a toxicology unit between August 2010 and December 2017. Our database yielded patients who underwent head CT at presentation to the ED. Pre‐specified information was compiled from the medical records.

Results

There were 6261 presentations of which 1142 underwent head CT (17%). Median age was 41 years, and 437 (38%) were female. There were 492 (43%) recreational ingestions and 466 (41%) deliberate self‐poisonings. The commonest agents were sedatives 376 (33%) and opioids 282 (24%); 334 (29%) cases were intubated. Signs of head injury were found in 153 cases (13%) and focal neurological signs in 68 (6%). No acute pathology was reported in 884 head CTs (77%), chronic changes in 193 (17%) and incidental findings in 26 (2%). Acute pathology was found in 39 (4%) patients: 15 with hypoxic‐ischaemic injury, three infarctions, nine with intra‐cranial haemorrhage, 11 facial bone fractures and one retro‐bulbar haematoma. No patient required an immediate surgical intervention, and only one patient had a change to clinical treatment. Acute head CT pathology was associated with at least one of the following clinical features: need for intubation, signs of head injury, seizure, headache, and unexpected neurological signs.

Conclusion

Non‐contrast head CT is a low‐yield investigation in patients presenting with poisoning. Consideration should be given as to whether the clinical presentation is consistent with the expected toxidrome and whether the patient would benefit from head CT.
Workplace reform: a new social contract for Australia
Authors: Lansbury Russell D
Published: March 2021

The COVID‐19 crisis impels us to think about the future of Australia in many dimensions and from different perspectives including our social, economic and governance structures. A new social contract at work in Australia should rest on three pillars: a full employment policy coupled with a strong safety net for those not able to find work; a comprehensive system of post‐secondary and vocational training, and easy transition between them; industrial relations reforms to provide a stronger voice for workers in decisions affecting them in the workplace. These pillars should be based not only on the historical experience of Australia but also draw on successful examples from elsewhere. The Nordic countries, for example, have based their social and economic systems on a social partnership approach that relies on voluntary cooperation between interest groups rather than legislation.
A library preparation optimized for metagenomics of RNA viruses
Authors: Gil Patricia , Dupuy Virginie , Koual Rachid , Exbrayat Antoni , Loire Etienne , Fall Assane G. , Gimonneau Geoffrey , Biteye Biram , Talla Seck Momar , Rakotoarivony Ignace , Marie Albane , Frances Benoît , Lambert Gregory , Reveillaud Julie , Balenghien Thomas , Garros Claire , Albina Emmanuel , Eloit Marc , Gutierrez Serafin
Published: March 2021

Our understanding of the viral communities associated to animals has not yet reached the level attained on the bacteriome. This situation is due to, among others, technical challenges in adapting metagenomics using high‐throughput sequencing to the study of RNA viromes in animals. Although important developments have been achieved in most steps of viral metagenomics, there is yet a key step that has received little attention: the library preparation. This situation differs from bacteriome studies in which developments in library preparation have largely contributed to the democratisation of metagenomics. Here, we present a library preparation optimized for metagenomics of RNA viruses from insect vectors of viral diseases. The library design allows a simple PCR‐based preparation, such as those routinely used in bacterial metabarcoding, that is adapted to shotgun sequencing as required in viral metagenomics. We first optimized our library preparation using mock viral communities and then validated a full metagenomic approach incorporating our preparation in two pilot studies with field‐caught insect vectors; one including a comparison with a published metagenomic protocol. Our approach provided a fold increase in virus‐like sequences compared to other studies, and nearly‐full genomes from new virus species. Moreover, our results suggested conserved trends in virome composition within a population of a mosquito species. Finally, the sensitivity of our approach was compared to a commercial diagnostic PCR for the detection of an arbovirus in field‐caught insect vectors. Our approach could facilitate studies on viral communities from animals and the democratization of metagenomics in community ecology of viruses.
The influence of pastoral and native forest land cover, flooding disturbance, and stream size on the trophic ecology of New Zealand streams
Authors: Fraley Kevin M. , Warburton Helen J. , Jellyman Phillip G. , Kelly Dave , McIntosh Angus R.
Published: March 2021

Describing trophic structure within freshwater food webs can be a useful tool for understanding relationships to make ecological inferences and to inform management action. A complementary analysis examining both stable isotope (SI) and biomass community components may be useful, because these two responses may be influenced differently by habitat factors and perturbations (e.g. flooding disturbance). To test this, stable isotope‐derived trophic height and biomass were characterised, as was coarse allochthonous, periphyton, invertebrate and fish components, for 27 stream communities in Canterbury, New Zealand. Using piecewise structural equation modelling to test relationships between components, it was found that increased catchment agricultural land cover was associated with increased periphyton biomass and δ15N (trophic height) in stream invertebrates and invertivorous fishes, likely due to nitrate runoff, but did not affect piscivorous fishes. Additionally, native forest land cover was associated with increased instream allochthonous biomass. Increased discharge (i.e. larger habitat size) did not affect the trophic height or biomass per‐unit‐area of large‐bodied piscivorous fishes (non‐native trout and native eels), although it did result in decreased biomass of small‐bodied invertivorous fishes (primarily native benthic taxa), likely due to high water velocities in larger habitats rendering habitat less suitable for small‐bodied fishes. Finally, flooding disturbance negatively affected both trophic height and biomass of large‐bodied fishes, but did not affect small‐bodied invertivorous fishes. Overall, describing stream trophic structure with complementary SI and biomass structural equation models appears to be a useful approach for constructing an integrative picture of how abiotic and biotic habitat factors affect freshwater communities. Our findings indicate that land cover, stream size and flooding disturbance should be taken into consideration by stream managers when conducting habitat restoration efforts or setting fish harvest regulations.
The Limits of Resilience: Managing Waste in the Racialized Anthropocene
Authors: Resnick Elana
Published: March 2021

Recent anthropological attention to more‐than‐human life has neglected the importance of race and racialization in human responses to environmental change. Drawing on ethnographic fieldwork with waste management institutions and Romani waste laborers in urban Bulgaria, this article invokes the concept of the racialized Anthropocene to destabilize the unmarked whiteness upon which the turn to humans‐as‐a‐species—anthropos—is founded. Habituation is central to both EU waste policy and the generative strategies Romani street sweepers use to manage accumulated waste and the conditions of their racialized labor. I call these creative and quotidian strategies anthropogenic management. Anthropogenic management disrupts the resiliency paradigm that has become commonplace in analyses of how people respond to circumstances not of their own making. As such, it bridges the Anthropocene, marked by waste accumulation at a planetary scale, with the everyday conditions of racialization through the embodied labor of managing other people's trash. [waste, labor, race, Bulgaria]
Love as understanding
Authors: MAQSOOD AMMARA
Published: March 2021

In middle‐class Pakistan, marriage is the prescribed future for all women, but premarital contact between the sexes is discouraged. To find the right partner, then, without visibly flouting social norms, requires a skillful balancing act between private interests and aspirations, and between public representations and collective concerns. Young women often navigate these conflicting demands by developing what they call an understanding: a secret premarital relationship that they normalize by involving family at a late stage to orchestrate an arranged marriage. Firmly enmeshed within the social life of joint families, understandings are an instance neither of defying patriarchal norms nor of pursuing self‐cultivation within them. Instead, they offer a window into how young women live and explore new possibilities within the vestiges of normative structures. [love, marriage, desire, morality, consumption, joint family, Lahore, Pakistan]
Criteria for placenta accreta spectrum in the International Federation of Gynaecology and Obstetrics classification, and topographic invasion area are associated with massive hemorrhage in patients with placenta previa
Authors: Ishibashi Hiroki , Miyamoto Morikazu , Iwahashi Hideki , Matsuura Hiroko , Kakimoto Soichiro , Sakamoto Takahiro , Hada Taira , Takano Masashi
Published: March 2021

Introduction

Placenta previa with placenta accreta spectrum (PAS) is a life‐threatening disease that results in massive hemorrhage. The clinical and histologic criteria of PAS were adopted according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. We aimed to investigate whether FIGO criteria and topography were associated with maternal complications in patients with placenta previa.

Material and methods

Patients with placenta previa who underwent cesarean section at our institution between January 2003 and December 2019 were identified. First, they were divided based on FIGO classification, as follows: Group A, with clinical criteria; Group B, with histologic criteria; and Group C: without clinical or histologic criteria. Next, cases with PAS were classified according to the topographic invasion area, as follows: type 1, upper posterior bladder; type 2, lower posterior bladder; type 3, parametrium; type 4, posterior lower uterine segment. Predictive factors for massive hemorrhage were retrospectively analyzed.

Results

Among the 350 patients, 24 (6.9%) were classified as Group A, 16 (4.6%) as Group B and 310 (88.5%) as Group C. Regarding maternal history and hemostatic procedures, there were no significant factors other than hysterectomy (p < .01) in Groups A and B. The volume of blood loss in both Groups A and B was greater than in Group C (p < .01). The rates of uterine artery embolization and blood transfusion were higher in Groups A and B than in Group C (p < .01). In addition, there were no significant factors other than hysterectomy between Groups A and B. In the multivariate analysis for massive hemorrhage, Group A (odds ratio: 2.73, p = .04) and Group B (odds ratio: 12.69, p < .01) were identified as independent predictive factors. In addition, massive hemorrhage was closely related to the lower posterior bladder and parametrial invasion in both Groups A and B.

Conclusions

Both clinical and histologic criteria for PAS in the FIGO classification were associated with massive hemorrhage. Diagnosing clinical PAS using the FIGO classification, additional hemostatic procedures might be necessary according to the topographic invasion area.
The Earned Income Tax Credit: Targeting the poor but crowding out wealth
Authors: Froemel Maren , Gottlieb Charles
Published: March 2021

This paper quantifies the individual, aggregate and welfare effects of the US Earned Income Tax Credit (EITC). In particular, we analyze the labour supply and saving responses to changes in tax credit generosity and their implications for prices and welfare. Our results show that the EITC is a subsidy on labour income and a tax on savings. An increase in EITC generosity raises labour force participation, reduces savings for many and provides insurance to working poor households. The EITC reduces earnings inequality but increases the skill premium and wealth inequality. A 10% increase in tax credit generosity increases welfare by 0.31% and benefits the majority of the population.
Can we better define stewardship for public sector executives? A research agenda
Authors: Simpkins Leah , Beaudry Myriam , Lemyre Louise
Published: March 2021

Building on an emerging body of literature, this research note aims to develop key features of stewardship through documenting the narratives of executives in the Canadian federal public service. Content analysis of interviews converged towards a conceptualization of stewardship based on four themes: 1) service over self‐interest, 2) sustainability of the public service beyond one’s career, 3) working with a collective orientation, and 4) mission‐focused management of resources. Results also revealed contextual factors fostering and hindering stewardship such as empowering work processes, collaboration practices and network facilitation. Implications of these results are discussed, as well as avenues for future research.
Learning From “Thinkers”: Parent Epistemological Understanding Predicts Individual Differences in Children’s Judgments About Reasoners
Authors: Suárez Sarah , Koenig Melissa A.
Published: March 2021

Four‐, 5‐, and 6‐year olds (N = 102) observed agents perform a reasoning task that required gathering hidden evidence. An agent who made sound inferences was contrasted with an agent who made either unsound inferences (UI; failed to base conclusion on gathered evidence) or guesses (failed to gather evidence). Four‐year olds attributed knowledge to all agents and endorsed their conclusions widely. However, 5‐ and 6‐year olds’ knowledge attributions were mitigated by UI, and 6‐year olds neither attributed knowledge to a guesser nor endorsed his conclusions. Notably, parents’ tendency to make evaluativist epistemological judgments—which place value in evidence as a basis for belief—predicted children’s reluctance to learn from and credit knowledge to poor reasoners. Parents’ evaluativist judgments also predicted children’s selective learning about object functions.
Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans
Authors: Simons Pomme I. H. G. , Valkenburg Olivier , Telgenkamp Ine , van der Waaij Koen M. , de Groot David M. , Veeraiah Pandichelvam , Bons Judith A. P. , Taskinen Marja‐Riitta , Borén Jan , Schrauwen Patrick , Rutten Joost H. W. , Cassiman David , Schalkwijk Casper G. , Stehouwer Coen D. A. , Schrauwen‐Hinderling Vera B. , Hodson Leanne , Brouwers Martijn C. G. J.
Published: March 2021

Objective

Obesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans.

Design

A cross‐sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex.

Participants

Healthy men (n = 34) and women (n = 21) were combined from two cross‐sectional studies. Forty‐two per cent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%).

Results

DNL was inversely associated with SHBG in women (β: −0.015, 95% CI: −0.030; 0.000), but not in men (β: 0.007, 95% CI: −0.005; 0.019) (p for interaction = .068). Adjustment for study population, age and body mass index did not materially change these results, although statistical significance was lost after adjustment for serum insulin.

Conclusions

An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.
In patients with controlled acromegaly, indices of glucose homeostasis correlate with IGF‐1 levels rather than with type of treatment
Authors: Decock Amelie , Verroken Charlotte , Van de Velde Frederique , Vilsbøll Tina , Holst Jens Juul , T'Sjoen Guy , Lapauw Bruno
Published: March 2021

Objective

Acromegaly is accompanied by abnormalities in glucose and lipid metabolism which improve upon treatment. Few studies have investigated whether these improvements differ between treatment modalities. This study aimed to compare glucose homeostasis, lipid profiles and postprandial gut hormone response in patients with controlled acromegaly according to actual treatment.

Design

Cross‐sectional study at a tertiary care centre.

Patients

Twenty‐one patients with acromegaly under stable control (ie insulin growth factor 1 [IGF1] levels below sex‐ and age‐specific thresholds and a random growth hormone level <1.0 µg/L) after surgery (n = 5), during treatment with long‐acting somatostatin analogues (n = 10) or long‐acting somatostatin analogues + pegvisomant (n = 6) were included.

Measurements

Glucose, insulin, total cholesterol and high‐density lipoprotein‐cholesterol were measured in fasting serum samples. Glucose, insulin, triglycerides, glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide 1 were measured during a mixed meal test. Insulin sensitivity was evaluated by a hyperinsulinaemic‐euglycaemic clamp.

Results

There were no significant differences in glucose tolerance, insulin sensitivity or postprandial gut hormone responses between the three groups. Positive correlations between IGF1 levels and HbA1c, fasting glucose and insulin levels and postprandial area under the curve (AUC) of glucose and insulin and also an inverse association between IGF1 and glucose disposal rate were found in the whole cohort (all p < .05, lowest p = .001 for postprandial AUC glucose with rs = 0.660).

Conclusion

In this cross‐sectional study in patients with controlled acromegaly, there were no differences in glucose homeostasis or postprandial substrate metabolism according to treatment modality. However, a lower IGF1 level seems associated with a better metabolic profile.
GCH1 mutations in hereditary spastic paraplegia
Authors: Varghaei Parizad , Yoon Grace , Estiar Mehrdad A. , Veyron Simon , Leveille Etienne , Dupré Nicolas , Trempe Jean‐François , Rouleau Guy A. , Gan‐Or Ziv
Published: March 2021

GCH1 mutations have been associated with dopa‐responsive dystonia (DRD), Parkinson's disease (PD) and tetrahydrobiopterin (BH4)‐deficient hyperphenylalaninemia B. Recently, GCH1 mutations have been reported in five patients with hereditary spastic paraplegia (HSP). Here, we analyzed a total of 400 HSP patients (291 families) from different centers across Canada by whole exome sequencing (WES). Three patients with heterozygous GCH1 variants were identified: monozygotic twins with a p.(Ser77_Leu82del) variant, and a patient with a p.(Val205Glu) variant. The former variant is predicted to be likely pathogenic and the latter is pathogenic. The three patients presented with childhood‐onset lower limb spasticity, hyperreflexia and abnormal plantar responses. One of the patients had diurnal fluctuations, and none had parkinsonism or dystonia. Phenotypic differences between the monozygotic twins were observed, who responded well to levodopa treatment. Pathway enrichment analysis suggested that GCH1 shares processes and pathways with other HSP‐associated genes, and structural analysis of the variants indicated a disruptive effect. In conclusion, GCH1 mutations may cause HSP; therefore, we suggest a levodopa trial in HSP patients and including GCH1 in the screening panels of HSP genes. Clinical differences between monozygotic twins suggest that environmental factors, epigenetics, and stochasticity could play a role in the clinical presentation.
Association between periodontitis treatment outcomes and peri‐implantitis: A long‐term retrospective cohort study
Authors: Vagia Panagiota , Papalou Ioanna , Burgy Alexandre , Tenenbaum Henri , Huck Olivier , Davideau Jean‐Luc
Published: March 2021

Objectives

Retrospectively evaluate the association of periodontal treatment outcomes and the prevalence of peri‐implant diseases around tissue‐level implants.

Materials and Methods

Eighty‐six patients with 260 tissue‐level implants attending supporting periodontal and implant therapy for more than 3 years were evaluated. Clinical and radiographic periodontal and implant data were recorded at initial examination (T0), before implant placement (T1) and at final re‐examination (T2). Two definitions of peri‐implantitis severity, PIBE and PIKA, were used corresponding to the presence of periodontal pocket ≥5 mm or ≥6 mm with bleeding on probing or suppuration and radiographic signs of a bone level ≥2 mm, or ≥3 mm during implant follow‐up, respectively. Analyses were performed at patient level.

Results

The mean implant follow‐up per patient was 9.4 years and 38.0% of patients had implant for at least 10 years. Two implants were lost due to peri‐implantitis. The prevalence of patients with PIKA and PIBE was 15.1% and 12.8%, respectively. Residual periodontal pockets, clinical attachment loss and bone loss/age at T2 were more pronounced in patients with PIKA and PIBE. Cox regression analysis adjusted with the number of implants per patient showed that residual pockets at T1 were independently associated with PIKA and PIBE. Initial diagnosis of severe periodontitis was associated with PIBE incidence.

Conclusions

The present study showed that periodontal conditions before implant placement are a risk indicator for peri‐implantitis incidence. During implant follow‐up, the severity of periodontal status appeared to be a reliable indicator of patient susceptibility to peri‐implantitis.
Activation of the glucocorticoid receptor rapidly triggers calcium‐dependent serotonin release in vitro
Authors: Paul Nicolas , Raymond Justine , Lumbreras Sara , Bartsch Dusan , Weber Tillmann , Lau Thorsten
Published: March 2021

Aims

Glucocorticoids rapidly provoke serotonin (5‐HT) release in vivo. We aimed to investigate molecular mechanisms of glucocorticoid receptor (GR)‐triggered 5‐HT release.

Methods

Employing 1C11 cells to model 5‐HT neurotransmission, immunofluorescence and Pearson's Correlation Coefficient were used to analyze colocalization of GR, 5‐HT, vesicle membrane protein synaptotagmin 1 and vesicle dye FM4‐64FX. FFN511 and FM4‐64FX dyes as well as calcium imaging were used to visualize vesicular 5‐HT release upon application of GR agonist dexamethasone, GR antagonist mifepristone and voltage‐gated calcium channel (VGCC) inhibitors.

Results

GR, 5‐HT, synaptotagmin 1 and FM4‐64FX showed overlapping staining patterns, with Pearson's Correlation Coefficient indicating colocalization. Similarly to potassium chloride, dexamethasone caused a release of FFN511 and uptake of FM4‐64FX, indicating vesicular 5‐HT release. Mifepristone, calcium depletion and inhibition of L‐type VGCC significantly diminished dexamethasone‐induced vesicular 5‐HT release.

Conclusions

In close proximity to 5‐HT releasing sites, activated GR rapidly triggers L‐type VGCC‐dependent vesicular 5‐HT release. These findings provide a better understanding of the interrelationship between glucocorticoids and 5‐HT release.
Nickel release from metallic earrings: A survey of the Danish market and validation of the nickel spot test
Authors: Wennervaldt Michael , Ahlström Malin G. , Menné Torkil , Thyssen Jacob P. , Johansen Jeanne D.
Published: March 2021

Background

Exposure to nickel releasing ear piercing jewellery may explain the persistently high prevalence of nickel allergy in Europe. While nickel release from earrings is regulated, field studies show that the regulation is not always respected. More knowledge is needed regarding the risk of piercing exposure including suitable screening methods.

Objective

To examine the proportion of earrings on the Danish market that release more nickel than allowed, and to validate the use of the dimethylglyoxime (DMG) test as a screening tool.

Methods

A total of 304 earrings were purchased and tested with the DMG test and X‐ray fluorescence spectrometry. The level of nickel release was quantified in a selected subsample of 100 earrings by the European reference test EN 1811. The DMG spot test was validated against EN 1811 at different thresholds.

Results

Excessive nickel release according to the European regulation was found in 45 (14.8%) tested earrings. The sensitivity of the DMG test decreased with reduced levels of nickel release (sensitivity of 45.2% at ≥0.2 μg/cm2/week vs 61.1% at >0.5 μg/cm2/week).

Conclusion

Excessive nickel release is common in earrings on the Danish market. Because of low sensitivity, the DMG test has limited use in screening of earrings for research but may still be used clinically.
Colonoscopy quality indicators in patients with and without prior colonic resection: A single‐centre prospective comparative study
Authors: Bhat Sameer , Wells Cameron I. , Tan Jeffrey , Bissett Ian P. , Lill Marianne
Published: March 2021

Aim

Effective colonoscopy relies on meeting rigorous quality control thresholds. Some earlier studies evaluating colonoscopy key performance indicators (KPIs) have excluded patients who have previously undergone colonic resection (i.e., they have a nonintact colon); such patients also deserve high‐quality colonoscopy. This study aimed to compare colonoscopy KPIs between patients with nonintact and intact colons.

Method

Consecutive colonoscopies performed at Whanganui Hospital (New Zealand) between September 2016 and March 2020 were included. The primary outcome was the caecal or ileal intubation rate (CIIR). Secondary outcomes were the adenoma detection rate (ADR), polyp detection rate (PDR), colonoscope withdrawal time (CWT) and caecal or ileal intubation time (CIIT).

Results

In total, 3017 colonoscopies were performed: 322 in nonintact colons and 2695 in intact colons. CIIR was significantly higher in nonintact than in intact colons (98.4% vs. 95.0%; P = 0.0086). When all colonoscopies were included, the CIIR was 95.4%; this value decreased to 95.0% when nonintact colonoscopies were excluded. However, the ADR (39.9% vs. 38.8%; P = 0.77) and PDR (58.4% vs. 59.1%; P = 0.86) were similar for both nonintact and intact colons. CWT (P < 0.0001) and CIIT (P < 0.0001) were significantly shorter in participants with nonintact colons.

Conclusion

The CIIR exceeded recommended targets and was 3.4% higher in patients with nonintact than intact colons. Patients with nonintact colons comprise a small proportion of the overall colonoscopy cohort and it is unlikely that this small difference is relevant for most endoscopists or endoscopy units. The ADR and PDR were similar among patients with nonintact and intact colons, despite nonintact colonoscopies being significantly quicker. Patients with nonintact colons deserve high‐quality colonoscopy and therefore their KPIs should be included in colonoscopy performance reports.
Coexistence of three nevus lipomatosus cutaneus superficialis with typical, cutaneous adenolipoma‐like, and dermal spindle cell lipoma‐like histopathological features in a patient
Authors: Shiomi Tatsushi , Matsuno Mei , Nishimura Hirotake , Moriya Takuya
Published: March 2021

We report an unique case of a patient who showed coexistence of three nevus lipomatosus cutaneus superficialis (NLCS) with typical, cutaneous adenolipoma (AL)‐like, and dermal spindle cell lipoma (SCL)‐like histopathological features. A 53‐year‐old woman presented with a 20‐year history of skin‐colored and slightly elevated nodules. These lesions were separately located on the lateral side (lesion 1) and medial side (lesion 2) of her left buttock and on her right thigh (lesion 3). Microscopically, all were ill‐defined dermal lesions with some subcutaneous involvement and were mostly composed of mature adipocytes. The adipocytes formed small aggregates around blood vessels in the upper dermis. Lesions 1, 2, and 3 were diagnosed as NLCS, and additional features were recognized in lesions 2 and 3. Lesion 2 revealed eccrine glands and ducts amongst the lipomatous component, as seen in cutaneous AL. Lesion 3 had scattered CD34‐positive spindle cells, which is representative of dermal SCL. These appearances were considered to be on the morphological spectrum of NLCS. In all three lesions, CD34‐positive cells proliferated between the upper dermal blood vessels and their peripheral mature adipocytes. This pathological finding could be principal in NLCS and might be associated with its pathogenesis.
Alcohol and cocaine use prior to suspected suicide: Insights from toxicology
Authors: Bailey James , Kalk Nicola J. , Andrews Rebecca , Yates Sarah , Nahar Limon , Kelleher Michael , Paterson Susan
Published: March 2021

Introduction

This study investigates whether there is a relationship between alcohol and cocaine use in deaths where suicide by self‐injury is the suspected cause of death.

Methods

Adults referred by coroners to the Imperial College London Toxicology Unit for toxicological analysis between 2012 and 2016 were reviewed for inclusion criteria. Those who died by self‐injury reasoned to be deliberate were included in the analysis. Femoral blood alcohol concentration (BAC) and presence of cocaine or benzoylecognine (a metabolite of cocaine) in blood and/or urine were tabulated and odds ratios calculated.

Results

A total of 1722 decedents met inclusion criteria. BAC was ≥50 mg/dL in 29% of decedents. Cocaine was detected in 8.4% of cases. The likelihood of testing positive for cocaine increased with BAC and was most frequent between 100 and 199 mg/dL, consistent with moderate to severe intoxication (odds ratio 5.88, 95% confidence interval 3.80, 9.09; P ≤ 0.001) compared to those with BAC <10 mg/dL.

Discussion and Conclusions

This study demonstrates a correlation between increasing BAC and likelihood of cocaine use prior to suspected suicide, up to a level consistent with severe intoxication. Cocaine use was found in a high proportion of cases relative to the general population reporting regular use. This pattern of drug and alcohol use has previously been given little attention in suicide prevention strategies and clinical prioritisation.
Quantifying nicotine and alcohol consumption in New Zealand using wastewater‐based epidemiology timed to coincide with census
Authors: Trowsdale Sam , Price Mackay , Wilkins Chris , Tscharke Ben , Mueller Jochen , Baker Tom
Published: March 2021

Introduction

Accurate and timely information about nicotine and alcohol consumption is needed to inform effective policy. Wastewater‐based epidemiology provides an opportunity to quantify consumption, which can complement traditional data collection methods.

Methods

Wastewater samples were collected from seven wastewater treatment plants on seven consecutive days in three regions of New Zealand during the same week as the national census (6 March 2018). Samples were analysed for nicotine and alcohol metabolites using liquid chromatography–tandem mass spectrometry. Detailed catchment maps were developed and per capita consumption calculated.

Results

Observed nicotine consumption (mean 1528 ± 412 cigarettes/day/1000 people) was similar to national sales data. Observed alcohol consumption (mean 1155 ± 764 standard drinks/day/1000 people) was lower than estimated using alcohol availability data. Consumption of nicotine and alcohol was generally higher in the Bay of Plenty and Canterbury compared to Auckland, mirroring trends in the New Zealand Health Survey. Intra‐regional differences were observed and the patterns could not be attributed to urbanisation alone. Nicotine consumption was consistent throughout the week whereas alcohol consumption often peaked at the weekend. Nicotine consumption was correlated with neighbourhood‐deprivation. There was little correlation for alcohol.

Discussion and Conclusions

Wastewater‐based epidemiology provides a quantitative dataset that complements traditional methods of investigating nicotine and alcohol consumption. Timing data collection to coincide with the census helps to account for the influence of population mobility when normalising consumption.