bluuebunny/crossref_metadata_2025 huggingface dataset:
Prefrontal solution to the bias-variance tradeoff during reinforcement learning
Authors: Kim Dongjae , Jeong Jaeseung , Lee Sang Wan
Published: December 2020

The goal of learning is to maximize future rewards by minimizing prediction errors. Evidence have shown that the brain achieves this by combining model-based and model-free learning. However, the prediction error minimization is challenged by a bias-variance tradeoff, which imposes constraints on each strategy’s performance. We provide new theoretical insight into how this tradeoff can be resolved through the adaptive control of model-based and model-free learning. The theory predicts the baseline correction for prediction error reduces the lower bound of the bias–variance error by factoring out irreducible noise. Using a Markov decision task with context changes, we showed behavioral evidence of adaptive control. Model-based behavioral analyses show that the prediction error baseline signals context changes to improve adaptability. Critically, the neural results support this view, demonstrating multiplexed representations of prediction error baseline within the ventrolateral and ventromedial prefrontal cortex, key brain regions known to guide model-based and model-free learning.

One sentence summary

A theoretical, behavioral, computational, and neural account of how the brain resolves the bias-variance tradeoff during reinforcement learning is described.
Universal salt iodization contributes to health equity: socio-economic status does not affect iodine status in children in Macedonia
Authors: Kostova Neda Milevska , Karanfilski Borislav , Miladinova Daniela , Kuzmanovska Sonja , Chuleva Biljana , Majstorov Venjamin , Ittermann Till , Völzke Henry
Published: December 2020

Many studies have shown that socio-economic status (SES) contributes to health inequalities, with nutrition as one of the major risk factors. Iodine intake entirely depends on external sources, and deficiencies are known to be more prevalent in lower social groups, especially in countries with limited access to iodized salt. This study aimed to determine the influence of SES on iodine status and iodine availability from household salt in North Macedonia. Using cluster sampling, 1,200 children were recruited, and 1,191 children participated (response rate: 99.2%). Iodine status was assessed through urinary iodine concentration (UIC), and iodine availability through iodine content in household salt requested from participants. SES was assessed using standardized Family Affluence Score (FAS). No statistically significant correlation was found between FAS and iodine in salt. Median regression revealed no significant associations of middle vs. low FAS (β=0.00; 95%-confidence interval (CI)=[−0.61, 0.62]; p=0.999) or high vs. low affluence (β=0.48; 95%CI=[−1.37, 0.41]; p=0.291) with iodine content in household salt. UIC levels were significantly lower in middle FAS children compared to low FAS children (β=-16.4; 95%CI=[−32.3,-0.5]; p=0.043). No statistically significant differences in UIC were found between children with high and low affluence (β=-12.5; 95%CI=[−35.5, 10.5]; p=0.287), possibly due to lowered statistical power for this comparison. Universal salt iodization (USI) proves to be cost-effective measure for appropriate iodine intake in healthy children and adults, irrespective of their social status. It can thus be concluded that USI contributes to reducing health inequalities related to iodine status among population of different social strata.
Generalized conditions for coexistence of competing parasitoids on a shared host
Authors: Singh Abhyudai
Published: December 2020

Motivated by the univoltine life histories of insects residing in the temperate-regions of the world, there is a rich tradition of modeling arthropod host-parasitoid interactions using a discrete-time formalism. We introduce a general class of discrete-time models for capturing the population dynamics of two competing parasitoid species that attack the same vulnerable stage of the host species. These models are characterized by two density-dependent functions: anescape responsedefined by the fraction of hosts escaping parasitism; and acompetition responsedefined by the fraction of parasitized hosts that develop into adult parasitoids of either species. Model analysis reveals remarkably simple stability conditions for the coexistence of competing parasitoids. More specifically, coexistence occurs, if and only if, the adult host density increases with host reproduction rate, and the log sensitivity of the competition response is less than half. The latter condition implies that any increase in the adult parasitoid density will result in a sufficiently slow increase in the fraction of parasitized hosts that develop into parasitoids of that type. We next consider a model motivated by differences in parasitism risk among individual hosts with risk from the two parasitoid species assumed to be independently distributed as per a Gamma distribution. In such models, the heterogeneity in host risk to each parasitoid is quantified by the corresponding Coefficient of Variation (CV). Our results show that parasitoid coexistence occurs for sufficiently large reproduction rate, if and only if, the sum of the inverse of the two CV squares is less than one. This result generalizes the “CV greater than one” rule that defined the stability for a single parasitoid-host system to a multi parasitoid-host community.
Multidimensional brain-age prediction reveals altered brain developmental trajectory in psychiatric disorders
Authors: Niu Xin , Taylor Alexei , Shinohara Russell T. , Kounios John , Zhang Fengqing
Published: December 2020

Neuroimaging-based brain-age prediction has emerged as an important new approach for studying brain development. However, brain regions change in different ways and at different rates. Unitary brain-age indices used in previous studies represent developmental status averaged across the whole brain and therefore do not capture the divergent developmental trajectories of various brain structures. Importantly, this staggered developmental unfolding, determined by genetics and postnatal experience, is implicated in the progression of psychiatric and neurological disorders. Here we propose an analytic method for computing a multidimensional brain-age index (MBAI) that provides regional age predictions. Using a database of 556 subjects (ages 8-21) that includes psychiatric and neurological patients as well as healthy controls, we conducted robust regression and cluster analyses to identify clusters of imaging features with distinct developmental trajectories. We then built machine-learning models to obtain brain-age predictions from each of the identified clusters to form the MBAI. Our results show that the MBAI provides a flexible analysis of region-specific brain-age changes that are invisible to unidimensional brain-age prediction methods. Importantly, brain ages computed from region-specific feature clusters contain complementary information and demonstrate differential ability to classify disorder groups (e.g., specific phobia, depression, ADHD) from healthy controls. Compared to unidimensional brain-age indices, we show that the MBAI is sensitive to alterations in brain structures and captures distinct regional change patterns which may serve as biomarkers that may contribute to our understanding of healthy and pathological brain development and to the characterization, diagnosis, and, potentially, treatment of various disorders.
The maximum surface area polyhedron with five vertices inscribed in the sphere {\bb S}^{2}
Authors: Donahue Jessica , Hoehner Steven , Li Ben
Published: December 2020

This article focuses on the problem of analytically determining the optimal placement of five points on the unit sphere {\bb S}^{2} so that the surface area of the convex hull of the points is maximized. It is shown that the optimal polyhedron has a trigonal bipyramidal structure with two vertices placed at the north and south poles and the other three vertices forming an equilateral triangle inscribed in the equator. This result confirms a conjecture of Akkiraju, who conducted a numerical search for the maximizer. As an application to crystallography, the surface area discrepancy is considered as a measure of distortion between an observed coordination polyhedron and an ideal one. The main result yields a formula for the surface area discrepancy of any coordination polyhedron with five vertices.
Urban household food waste: drivers and practices in Toronto, Canada
Authors: Li Belinda , Maclaren Virginia , Soma Tammara
Published: December 2020

Purpose

The purpose of this paper is to understand determinants of food waste through analysing patterns of practices including shopping, planning, consumption of leftovers and attitudes around best-before dates.

Design/methodology/approach

A survey and waste composition analysis of 142 households was conducted in the City of Toronto. Bivariate analyses and confirmatory factor analysis (CFA) using a structural equation model were used to identify relationships between per capita food waste, household socio-demographic characteristics and household food practices.

Findings

Constructs related to planning practices and best-before date practices were identified through the CFA. Household size and the best-before construct were negatively correlated with per capita food waste. The planning construct had no correlation, which may be attributed to the influence of the retail environment in encouraging unplanned purchases. The best-before construct was significantly correlated with the presence of children in the home, an indicator of the compromises that parents make in domestic provisioning to ensure healthy foods for their children, such as more caution in handling items after their best-before dates.

Originality/value

This is the first study of its kind that uses directly measured per capita food waste from a waste composition study in a structural equation model with a construct related to best-before dates to determine drivers of food waste. It is also the first to find that children in the home can have an indirect influence on food waste through the household's best-before practices.
Is animal welfare a central issue for consumers of luxury goods?
Authors: Achabou Mohamed Akli
Published: December 2020

The compatibility between luxury and sustainable development has been increasingly examined in recent literature, but a number of ethical issues remain unexplored. One such concern is animal welfare, a recurrent question in the luxury goods sector. This is one of the first research articles to shed light on this subject, utilising two studies, one qualitative and the other quantitative with conjoint analysis, conducted among 12 and 253 French consumers, respectively. The results reveal that consumers are sensitive to the challenge of animal welfare in luxury, but fall into two different groups. Some have a preference for animal‐based raw materials sourced from livestock farms that respect animal welfare, whilst others are more favourable to the use of synthetic raw materials. In particular, the results show that the use of synthetic raw materials is accepted by some consumers but can lead to a reduction in the perceived value of luxury products.
Epidemiology of thymic epithelial tumors: 22‐years experience from a single‐institution
Authors: Rioja Patricia , Ruiz Rossana , Galvez‐Nino Marco , Lozano Sophia , Valdiviezo Natalia , Olivera Mivael , Cabero Octavio , Guillen Maria Eugenia , De La Guerra Alberto , Amorin Edgar , Barrionuevo Carlos , Mas Luis
Published: December 2020

Background

To assess the correlation of WHO histological classification and Masaoka–Koga staging system of thymic epithelial tumors (TETs) with prognosis.

Methods

We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka–Koga staging system. Survival curves were constructed with Kaplan‐Meir method.

Results

There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III–IV) was high (65%). With a median follow‐up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka–Koga staging had an effect on survival.

Conclusions

The results indicates a clear association between the WHO histological classification and Masaoka–Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment.

Key points

Significant findings of the study

The WHO histological classification, the Masaoka–Koga system and surgery treatment were associated with overall survival.

What this study adds

To determine prognosis factors in TETs.
Mitochondrial DNA in extracellular vesicles declines with age
Authors: Lazo Stephanie , Noren Hooten Nicole , Green Jamal , Eitan Erez , Mode Nicolle A. , Liu Qing‐Rong , Zonderman Alan B. , Ezike Ngozi , Mattson Mark P. , Ghosh Paritosh , Evans Michele K.
Published: December 2020

The mitochondrial free radical theory of aging suggests that accumulating oxidative damage to mitochondria and mitochondrial DNA (mtDNA) plays a central role in aging. Circulating cell‐free mtDNA (ccf‐mtDNA) isolated from blood may be a biomarker of disease. Extracellular vesicles (EVs) are small (30–400 nm), lipid‐bound vesicles capable of shuttling proteins, nucleic acids, and lipids as part of intercellular communication systems. Here, we report that a portion of ccf‐mtDNA in plasma is encapsulated in EVs. To address whether EV mtDNA levels change with human age, we analyzed mtDNA in EVs from individuals aged 30–64 years cross‐sectionally and longitudinally. EV mtDNA levels decreased with age. Furthermore, the maximal mitochondrial respiration of cultured cells was differentially affected by EVs from old and young donors. Our results suggest that plasma mtDNA is present in EVs, that the level of EV‐derived mtDNA is associated with age, and that EVs affect mitochondrial energetics in an EV age‐dependent manner.
Shortening the Edinburgh postnatal depression scale using optimal test assembly methods: Development of the EPDS‐Dep‐5
Authors: Harel Daphna , Levis Brooke , Ishihara Miyabi , Levis Alexander W. , Vigod Simone N. , Howard Louise M. , Thombs Brett D. , Benedetti Andrea ,   the DEPRESsion Screening Data (DEPRESSD) EPDS Collaboration
Published: December 2020

Aims

This study used a large database to develop a reliable and valid shortened form of the Edinburgh Postnatal Depression Scale (EPDS), a self‐report questionnaire used for depression screening in pregnancy and postpartum, based on objective criteria.

Methods

Item responses from the 10‐item EPDS were obtained from 5157 participants (765 major depression cases) from 22 primary screening accuracy studies that compared the EPDS to the Structured Clinical Interview for DSM (SCID). Unidimensionality of the EPDS latent construct was verified using confirmatory factor analysis, and an item response theory model was fit. Optimal test assembly (OTA) methods identified a maximally informative shortened form for each possible scale length between 1 and 9 items. The final shortened form was selected based on pre‐specified validity and reliability criteria and non‐inferiority of screening accuracy of the EPDS as compared to the SCID.

Results

A 5‐item short form of the EPDS (EPDS‐Dep‐5) was selected. The EPDS‐Dep‐5 had a Cronbach's alpha of 0.82. Sensitivity and specificity of the EPDS‐Dep‐5 for a cutoff of 4 or greater were 0.83 (95% CI, 0.73, 0.89) and 0.86 (95% CI, 0.80, 0.90) and were statistically non‐inferior to the EPDS. The correlation of total scores with the full EPDS was high (r = 0.91).

Conclusion

The EPDS‐Dep‐5 is a valid short form with minimal loss of information when compared to the full‐length EPDS. The EPDS‐Dep‐5 was developed with OTA methods using objective, pre‐specified criteria, but the approach is data‐driven and exploratory. Thus, there is a need to replicate results of this study in different populations.
Elevational shifts in phylogenetic diversity of angiosperm trees across the subtropical Brazilian Atlantic Forest
Authors: Bergamin Rodrigo S. , Seger Guilherme D. S. , Carlucci Marcos B. , Molz Martin , Mello Ricardo S. P. , Martins Rafael , Jarenkow João A. , Brack Paulo , Müller Sandra C. , Duarte Leandro D. S.
Published: December 2020

Elevation gradients are drivers of species diversity, and, recently, studies have considered the evolutionary process in shaping community assembly patterns. Patterns of plant species richness across elevational gradients have been studied in different parts of the Atlantic Forest; however, little is known about plant phylogenetic diversity patterns. Thus, we aimed to analyse the phylogenetic diversity of angiosperm trees along an elevation gradient in southern Brazilian Plateau, in the subtropical portion of the Atlantic Forest. We expected a decrease in phylogenetic diversity along the elevation gradient, from lowlands towards to highlands, where species may be evolutionary closely related as many tropical lineages are not capable to inhabit colder conditions. We also investigated the distribution of phylogenetic clades along the elevation gradient through principal coordinates of phylogenetic structure. Data were obtained from 28 phytosociological surveys distributed across different elevation levels, ranging from 40 to 975 m. We found a negative association between phylogenetic diversity and the elevation gradient. The representativeness of families Myrtaceae and Lauraceae increased with elevation, while most of the families decreased in species richness and are replaced by temperate families such as Winteraceae (Drimys) in higher elevations. The decrease in phylogenetic diversity with increasing elevation may be linked to niche conservatism of tropical lineages that retain their historical climatic niches and thus many species are not capable to inhabit colder environments. Most tropical clades are restricted to lower elevations; however, Myrtaceae and Lauraceae probably evolved tolerance to colder temperatures during glacial cycles. Furthermore, the probably long‐term climate stability in lowlands than highland areas may have promoted the co‐occurrence of distantly related species, resulting in higher phylogenetic diversity. Finally, we observed how historical imprints and current environmental conditions shape the phylogenetic diversity of angiosperm tree species in subtropical Atlantic Forest.
Subfoveal choroidal thickness in ipsi‐ and contralateral eyes of patients with carotid stenosis before and after carotid endarterectomy: a prospective study
Authors: Ala‐Kauhaluoma Marianne , Koskinen Suvi M. , Silvennoinen Heli , Vikatmaa Pirkka , Nuotio Krista , Ijäs Petra , Relander Kristiina , Lindsberg Perttu J. , Soinne Lauri , Summanen Paula A.
Published: December 2020

Purpose

To compare subfoveal choroidal thickness (SFCT) and associated clinical variables in patients with carotid stenosis (CS) before and 6 months after carotid endarterectomy (CEA).

Methods

The prospective non‐randomized Helsinki Carotid Endarterectomy Study – Brain and Eye Sub‐sTudy included seventy patients (81% male, mean age 69 years) and 40 control subjects (77% male, 68 years), from March 2015 to December 2018. Ophthalmological examination included SFCT measured with enhanced‐depth imaging‐optical coherence tomography. Carotid stenosis (CS) was more severe (≥70% stenosis in 92%) ipsilateral to the CEA than contralaterally (<50% stenosis in 74%; p < 0.001).

Results

At baseline, patients had thinner mean SFCT than control subjects in both eyes (ipsilateral, 222 versus 257 μm and contralateral, 217 versus 258 μm, p ≤ 0.005). At follow‐up, SFCT did not change in ipsi‐ and contralateral eyes compared to baseline in patients (p = 0.68 and p = 0.77), or in control subjects (p = 0.59 and p = 0.79). Patients with coronary artery disease had thinner mean SFCT versus those without it in ipsilateral eyes before CEA (200 versus 233 μm, p = 0.027). In ipsilateral eyes of patients before CEA, thinner SFCT and ocular signs of CS, plaque and hypoperfusion related findings combined, were associated (p = 0.036), and the best‐corrected visual acuity, measured in logMAR, increased with increasing SFCT (r = −0.25; p = 0.046).

Conclusions

Subfoveal choroidal thickness (SFCT) is thinner in patients with CS without association between SFCT and the grade of CS. Unchanged SFCT after CEA suggests, that choroidal vessels in severe CS are unable to react to increased blood flow. Bilaterally thin SFCT could be considered as yet another sign of CS.
Retinal vascular oxygen saturation in response to a less extensive laser treatment in proliferative diabetic retinopathy
Authors: Vergmann Anna Stage , Torp Thomas Lee , Kawasaki Ryo , Hestoy Danjal Hofgaard , Wong Tien Yin , Peto Tunde , Grauslund Jakob
Published: December 2020

Purpose

The purpose of this study was to evaluate the association between retinal laser burden and vascular oxygen saturation in patients with proliferative diabetic retinopathy (PDR) treated with different extent of retinal laser.

Methods

The study was a prospective, interventional study of patients with treatment‐naïve PDR. Patients were treated with navigated retinal laser (Navilas®, OD‐OS GmbH, Teltow, Germany) in different doses. Retinal oximetry was obtained at baseline (BL) prior to laser and after 6 months (M6). Patients were divided into three groups according to total laser spots applied: <1500 spots (Group 1), 1500–2000 spots (Group 2), and >2000 spots (Group 3).

Results

We included 33 eyes of 28 patients with treatment‐naïve PDR. The groups did not differ according in BL characteristics. Between BL and M6, retinal arteriolar oxygen saturation did not change but retinal venular oxygen saturation (median with interquartile range) decreased in Groups 1 and 2 (1: 65.5 ± 8.8% versus 60.5 ± 9.5%, p = 0.04; 2: 65.3 ± 7.3% versus 63.0 ± 13.5%, p = 0.04). Focal retinal venular oxygen saturation, located to quadrants with retinal neovascularization, decreased in Group 2 from BL to M6 (67.5 ± 13.3% versus 61.5 ± 8.8%, p = 0.04). Retinal venular diameter decreased from BL to M6 in Group 1 (174.5 ± 15.3 μm versus 165.1 ± 28.7 μm, p = 0.01).

Conclusions

In this study of patients with treatment‐naïve PDR, we showed that a less extensive laser treatment caused a reduction in retinal venular oxygen saturation and diameter 6 months after treatment. Our results suggest that less extensive laser treatment may be sufficient to improve the retinal metabolic environment conducive to PDR regression.
Improved performance and safety from Argus II retinal prosthesis post‐approval study in France
Authors: Delyfer Marie‐Noëlle , Gaucher David , Mohand‐Saïd Saddek , Barale Pierre‐Olivier , Rezaigua‐Studer Fouzia , Ayello‐Scheer Sarah , Dollfus Hélène , Dorn Jessy D. , Korobelnik Jean‐François , Sahel José‐Alain
Published: December 2020

Purpose

To evaluate the post‐approval long‐term outcomes of the Argus II Retinal Prosthesis, with a specific focus on its functional visual benefit in patients’ daily activities.

Methods

Eighteen patients with bare light perception due to end‐stage retinitis pigmentosa were included in a French prospective, multicentre, single‐arm study and followed for 2 years. Visual benefit in patients’ daily activities was monitored through the use of the Functional Low‐vision Observer Rated Assessment (FLORA), and the final score at 2 years was the primary effectiveness outcome. Standardized visual assessments were also performed. Device‐ or procedure‐related adverse events were recorded.

Results

Seventeen subjects completed the study. Positive impacts of the Argus II system on functional vision and well‐being were demonstrated for over 70% of subjects on the FLORA. Among the daily activities/tasks tested, finding doorways was one of the most statistically significantly improved tasks (p < 0.001), along with estimating the size of an obstacle (p < 0.001), visually locating a place setting on a dining table (p < 0.001) and visually locating people in a non‐crowded setting (p < 0.001). Visual function was improved on most standardized tests. Only two device‐ or procedure‐related serious adverse events were observed (one vitreous haemorrhage and one endophthalmitis, both resolved with treatment). No explantation was required.

Conclusion

This first report of a completed post‐approval study of Argus II with a two‐year follow‐up demonstrates the safety and effectiveness of the Argus II System in a real‐world cohort of patients and further highlights its real functional benefit in implanted patients’ daily activities.
Glucose‐induced cAMP elevation in β‐cells involves amplification of constitutive and glucagon‐activated GLP‐1 receptor signalling
Authors: Shuai Hongyan , Xu Yunjian , Ahooghalandari Parvin , Tengholm Anders
Published: December 2020

Aim

cAMP typically signals downstream of Gs‐coupled receptors and regulates numerous cell functions. In β‐cells, cAMP amplifies Ca2+‐triggered exocytosis of insulin granules. Glucose‐induced insulin secretion is associated with Ca2+‐ and metabolism‐dependent increases of the sub‐plasma‐membrane cAMP concentration ([cAMP]pm) in β‐cells, but potential links to canonical receptor signalling are unclear. The aim of this study was to clarify the role of glucagon‐like peptide‐1 receptors (GLP1Rs) for glucose‐induced cAMP signalling in β‐cells.

Methods

Total internal reflection microscopy and fluorescent reporters were used to monitor changes in cAMP, Ca2+ and ATP concentrations as well as insulin secretion in MIN6 cells and mouse and human β‐cells. Insulin release from mouse and human islets was also measured with ELISA.

Results

The GLP1R antagonist exendin‐(9‐39) (ex‐9) prevented both GLP1‐ and glucagon‐induced elevations of [cAMP]pm, consistent with GLP1Rs being involved in the action of glucagon. This conclusion was supported by lack of unspecific effects of the antagonist in a reporter cell‐line. Ex‐9 also suppressed IBMX‐ and glucose‐induced [cAMP]pm elevations. Depolarization with K+ triggered Ca2+‐dependent [cAMP]pm elevation, an effect that was amplified by high glucose. Ex‐9 inhibited both the Ca2+ and glucose‐metabolism‐dependent actions on [cAMP]pm. The drug remained effective after minimizing paracrine signalling by dispersing the islets and it reduced basal [cAMP]pm in a cell‐line heterologously expressing GLP1Rs, indicating that there is constitutive GLP1R signalling. The ex‐9‐induced reduction of [cAMP]pm in glucose‐stimulated β‐cells was paralleled by suppression of insulin secretion.

Conclusion

Agonist‐independent and glucagon‐stimulated GLP1R signalling in β‐cells contributes to basal and glucose‐induced cAMP production and insulin secretion.
Safety of clonidine used for long‐term sedation in paediatric intensive care: A systematic review
Authors: Eberl Sonja , Ahne Gabriele , Toni Irmgard , Standing Joseph , Neubert Antje
Published: December 2020

Aim

Although not approved, the α‐adrenoceptor agonist clonidine is considered an option for long‐term sedation protocols in paediatric intensive care. We reviewed adverse effects of clonidine occurring in this indication.

Methods

Relevant literature was systematically identified from PubMed and Embase. We included interventional and observational studies on paediatric patients admitted to intensive care units and systemically long‐term sedated with clonidine‐containing regimes. In duplicates, we conducted standardised and independent full‐text assessment and extraction of safety data.

Results

Data from 11 studies with 909 patients were analysed. The studies were heterogeneous regarding patient characteristics (age groups, comorbidity, or comedication) and sedation regimes (dosage, route, duration, or concomitant sedatives). Just four randomised controlled trials (RCTs) and one observational study had comparison groups, using placebo or midazolam. For safety outcomes, our validity evaluation showed low risk of bias only in three studies. All studies focused on haemodynamic problems, particularly bradycardia and hypotension. Observed incidences or subsequent interventions never caused concerns. However, only two RCTs allowed meaningful comparisons with control groups. Odds ratios showed no significant difference between the groups, but small sample sizes (50 and 125 patients) must be considered; pooled analyses were not reasonable.

Conclusion

All evaluated studies concluded that the use of clonidine in paediatric intensive care units is safe. However, a valid characterisation of the safety profile remains challenging due to limited, biased and heterogeneous data and missing investigation of long‐term effects. This evaluation demonstrates the lack of data, which prevents reliable conclusions on the safety of clonidine for long‐term sedation in critically ill children. For an evidence‐based use, further studies are needed.
Curcumin attenuates renal interstitial fibrosis by regulating autophagy and retaining mitochondrial function in unilateral ureteral obstruction rats
Authors: Lu Miaomiao , Li Hang , Liu Wenlin , Zhang Xuemei , Li Lili , Zhou Hongli
Published: December 2020

Renal interstitial fibrosis (RIF) is the leading cause of end‐stage renal disease, partly because of the lack of effective treatments. Curcumin, the primary active ingredient in turmeric, reportedly exerts potent antifibrotic effects. This study investigated the effects of curcumin on RIF in unilateral ureteral obstruction (UUO) rats and characterized the underlying action mechanism. UUO rats were treated with curcumin for 7 and 14 d. Renal fibrosis was evaluated through haematoxylin‐eosin staining, Masson staining, and type I and III collagen expression. Autophagy and mitochondria were observed through scanning electron microscopy. NLRP3 inflammasomes, mitochondria, and autophagy‐related proteins were detected through Western blotting. Mitochondrial respiratory enzyme activity was assessed spectrophotometrically. Compared with UUO rats, renal fibrosis was attenuated and NLRP3 inflammasome activation was inhibited in curcumin‐treated rats. Furthermore, mitochondrial dysfunction was ameliorated and the LC3B/LC3A ratio and Beclin‐1 expression were increased in curcumin‐treated rats. Additionally, curcumin inhibited the PI3K/AKT/mTOR pathway. These results indicate that curcumin is a promising treatment agent for RIF, and its antifibrotic effects may be mediated by the inhibition of NLRP3 inflammasome activity through the regulation of autophagy and protection of mitochondrial function in UUO rats.
Prolonged interglacial warmth during the Last Glacial in northern Europe
Authors: Helmens Karin F. , Katrantsiotis Christos , Kuosmanen Niina , Luoto Tomi P. , Salonen J. Sakari , Väliranta Minna
Published: December 2020

Few fossil‐based environmental and climate records in northern Europe are dated to Marine Isotope Stage (MIS) 5a around 80 ka BP. We here present multiple environmental and climate proxies obtained from a lake sequence of MIS 5a age in the Sokli basin (northern Finland). Pollen/spores, plant macrofossils, NPPs (e.g. green algae), bryozoa, diatoms and chironomids allowed an exceptionally detailed reconstruction of aquatic and telmatic ecosystem successions related to the development of the Sokli Ice Lake and subsequent infilling of a relatively small and shallow lake confined to the Sokli basin. A regional vegetation development typical for the early half of an interglacial is recorded by the pollen, stomata and plant macrofossil data. Reconstructions of July temperatures based on pollen assemblages suffer from a large contribution of local pollen from the lake's littoral zone. Summer temperatures reaching present‐day values, inferred for the upper part of the lake sequence, however, agree with the establishment of pine‐dominated boreal forest indicated by the plant fossil data. Habitat preferences also influence the climate record based on chironomids. Nevertheless, the climate optima of the predominant intermediate‐ to warm‐water chironomid taxa suggest July temperatures exceeding present‐day values by up to several degrees, in line with climate inferences from a variety of aquatic and wetland plant indicator species. The disequilibrium between regional vegetation development and warm, insolation‐forced summers is also reported for Early Holocene records from northern Fennoscandia. The MIS 5a sequence is the last remaining fossil‐bearing deposit in the late Quaternary basin infill at Sokli to be studied using multi‐proxy evidence. A unique detailed climate record for MIS 5 is now available for formerly glaciated northern Europe. Our studies indicate that interglacial conditions persisted into MIS 5a, in agreement with data for large parts of the European mainland, shortening the Last Glacial by some 50 ka to MIS 4‐2.
Mitochondrial DNA variants in inclusion body myositis characterized by deep sequencing
Authors: Hedberg‐Oldfors Carola , Lindgren Ulrika , Basu Swaraj , Visuttijai Kittichate , Lindberg Christopher , Falkenberg Maria , Larsson Lekholm Erik , Oldfors Anders
Published: December 2020

Muscle pathology in inclusion body myositis (IBM) typically includes inflammatory cell infiltration, muscle fibers with rimmed vacuoles and cytochrome c oxidase (COX)‐deficient fibers. Previous studies have revealed clonal expansion of large mitochondrial DNA (mtDNA) deletions in the COX‐deficient muscle fibers. Technical limitations have prevented complete investigations of the mtDNA deletions and other mtDNA variants. Detailed characterization by deep sequencing of mtDNA in muscle samples from 21 IBM patients and 10 age‐matched controls was performed after whole genome sequencing with a mean depth of mtDNA coverage of 46,000x. Multiple large mtDNA deletions and duplications were identified in all IBM and control muscle samples. In general, the IBM muscles demonstrated a larger number of deletions and duplications with a mean heteroplasmy level of 10% (range 1%‐35%) compared to controls (1%, range 0.2%‐3%). There was also a small increase in the number of somatic single nucleotide variants in IBM muscle. More than 200 rearrangements were recurrent in at least two or more IBM muscles while 26 were found in both IBM and control muscles. The deletions and duplications, with a high recurrence rate, were mainly observed in three mtDNA regions, m.534‐4429, m.6330‐13993, and m.8636‐16072, where some were flanked by repetitive sequences. The mtDNA copy number in IBM muscle was reduced to 42% of controls. Immunohistochemical and western blot analyses of IBM muscle revealed combined complex I and complex IV deficiency affecting the COX‐deficient fibers. In conclusion, deep sequencing and quantitation of mtDNA variants revealed that IBM muscles had markedly increased levels of large deletions and duplications, and there were also indications of increased somatic single nucleotide variants and reduced mtDNA copy numbers compared to age‐matched controls. The distribution and type of variants were similar in IBM muscle and controls indicating an accelerated aging process in IBM muscle, possibly associated with chronic inflammation.
Compound heterozygosity for PTPN11 variants in a subject with Noonan syndrome provides insights into the mechanism of SHP2‐related disorders
Authors: Lorca Rebeca , Pannone Luca , Cuesta‐Llavona Elías , Bocchinfuso Gianfranco , Rodríguez‐Reguero Julian , Carpentieri Giovanna , Hernando Inés , Flex Elisabetta , Tartaglia Marco , Coto Eliecer , Gómez Juan , Martinelli Simone
Published: December 2020

The RASopathies are a family of clinically related disorders caused by mutations affecting genes participating in the RAS‐MAPK signaling cascade. Among them, Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) are allelic conditions principally associated with dominant mutations in PTPN11, which encodes the nonreceptor SH2 domain‐containing protein tyrosine phosphatase SHP2. Individual PTPN11 mutations are specific to each syndrome and have opposite consequences on catalysis, but all favor SHP2's interaction with signaling partners. Here, we report on a subject with NS harboring biallelic variants in PTPN11. While the former (p.Leu261Phe) had previously been reported in NS, the latter (p.Thr357Met) is a novel change impairing catalysis. Members of the family carrying p.Thr357Met, however, did not show any obvious feature fitting NSML or within the RASopathy phenotypic spectrum. A major impact of this change on transcript processing and protein stability was excluded. These findings further support the view that NSML cannot be ascribed merely to impaired SHP2's catalytic activity and suggest that PTPN11 mutations causing this condition act through an alternative dominant mechanism.
Costs of elephant crop depredation exceed the benefits of trophy hunting in a community‐based conservation area of Namibia
Authors: Drake Michael D. , Salerno Jonathan , Langendorf Ryan E. , Cassidy Lin , Gaughan Andrea E. , Stevens Forrest R. , Pricope Narcisa G. , Hartter Joel
Published: December 2020

The Kazavango‐Zambezi Transfrontier Conservation Area is home to the largest remaining elephant population in Africa but is also the site of high levels of human‐elephant conflict through crop depredation. Offsetting the costs of coexisting with elephants in this area is critical to incentivizing elephant conservation within community‐based conservation (CBC) areas, and trophy hunting has long been touted as a method for generating revenue for communities from wildlife. However, the idea that sustainable elephant hunting can offset the costs of crop depredation remains largely untested. We combined household survey data, financial records, and elephant population data to compare the potential benefits of sustainable hunting with the costs of crop depredation in a CBC area in northeastern Namibia. We determined that sustainable trophy hunting only returns ~30% of the value of crops lost to the community and cannot alone offset the current costs of coexistence with elephants. As core institutions supporting the practice of conservation, CBC efforts must promote community management capacity to combine multiple wildlife‐based income streams and build partnerships at multiple scales of governance to address the challenges of elephant management.
Is the theory of collectivity of drinking cultures valid across educational groups?
Authors: Landberg Jonas , Trolldal Björn , Norström Thor
Published: December 2020

Introduction

To explore whether Skog's theory of collectivity of drinking cultures is valid across groups with different socioeconomic position (SEP).

Methods

Individual‐level information on alcohol consumption and SEP for the years 2004–2014 were retrieved from the Monitoring Project; a nationally representative monthly alcohol use survey. The analytical sample consisted of 162 369 respondents aged 25–79 years. SEP was measured by education level. Alcohol use was measured by yearly volume of consumption and frequency of heavy episodic drinking (HED). Respondents were divided into six SEP‐groups based on their education level and sex. Mean yearly volume consumption and prevalence of monthly HED was calculated for each group and graphically plotted against the overall mean volume of consumption.

Results

The yearly changes in overall mean consumption during the study period reflected a collective shift in drinking across groups with basic, intermediate and high education. There were also indications that changes in overall mean consumption reflected collective shifts in the prevalence of HED across the SEP‐groups. Moreover, while the magnitude of the associations for both average volume and HED differed somewhat in strength across the SEP‐groups, they were clearly in the same, positive, direction.

Discussion and Conclusions

Our findings add support for including a socioeconomic dimension to Skog's theory of collectivity of drinking cultures. Future studies should replicate our analyses on cases and periods with more tangible changes in the price and availability of alcohol.
Checks and balances: a business‐oriented lens on disaster management and warnings
Authors: Mehta Amisha M. , Murray Scott , Hammill Cindy , Dootson Paula , Langdon Rebecca R.
Published: December 2020

Small businesses are critical to community recovery from disasters. However, factors that affect outcomes (such as planning, information needs, and responses to warnings) are understudied. To address the research record's focus on policy that favours disaster mitigation rather than response, this project applied a two‐phased, mixed‐method approach. The first study comprised interviews with businesses to elucidate disaster planning approaches, knowledge and information needs, and current warning system adequacy. It revealed opportunities to build knowledge and add business‐specific content to agency‐issued warnings. The second study used an online survey to examine how disaster knowledge, planning, and experience are related to existing bushfire warnings and those modified with business‐relevant content. The findings show that planning is associated with experience and knowledge but not with business‐related protective action intentions. Modified messages were perceived as more effective and resulted in greater action intentions among those with bushfire experience. In sum, the paper highlights implications for small business‐oriented disaster risk communication.
Factors associated with potential over‐ and undertreatment of hyperglycaemia and annual measurement of HbA1c in type 2 diabetes in norwegian general practice
Authors: Tran Anh T. , Berg Tore J. , Mdala Ibrahimu , Gjelsvik Bjørn , Cooper John G. , Sandberg Sverre , Claudi Tor , Jenum Anne K.
Published: December 2020

Aims

To identify individual and general practitioner (GP) characteristics associated with potential over‐ and undertreatment of hyperglycaemia in type 2 diabetes and with HbA1c not being measured.

Methods

A cross‐sectional study that included 10233 individuals with type 2 diabetes attending 282 GPs. Individuals with an HbA1c measurement during the last 15 months were categorized as potentially overtreated if they were prescribed a sulphonylurea and/or insulin when the HbA1c was less than 53 mmol/mol (7%) when aged over 75 years or less than 48 mmol/mol (6.5%) when aged between 65 and 75 years. Potential undertreatment was defined as age less than 60 years and HbA1c > 64 mmol/mol (8.0%) or HbA1c > 69 mmol/mol (8.5%) and treated with lifestyle modification and/or monotherapy. We used multilevel binary and multinominal logistic regression models to examine associations.

Results

Overall, 4.1% were potentially overtreated, 7.8% were potentially undertreated and 11% did not have HbA1c measured. Characteristics associated with potential overtreatment were as follows: long diabetes duration, prescribed antihypertensive medication, cardiovascular disease and renal failure. Potential undertreatment was associated with male gender, non‐western origin and low educational level. Characteristics associated with not having an HbA1c measurement performed were male gender, age < 50 years and cardiovascular diseases. GP specialist status and GPs’ use of a Noklus diabetes application reduced the risk of not having an HbA1c measurement performed.

Conclusion

Potential overtreatment in elderly individuals with type 2 diabetes was relatively low. Nevertheless, appropriate de‐intensification or intensification of treatment and regular HbA1c measurement in identified subgroups is warranted.
Losing My Connection: The Dark Side of Bank–Firm Interlocking Directorates
Authors: Barone Guglielmo , Mirenda Litterio , Mocetti Sauro
Published: December 2020

The paper examines the causal impact of bank–firm interlocking directorates on a firm’s access to credit. We exploit matched bank–firm panel data containing detailed information on individual loans and on the governing bodies of both the bank and the firm. Identification hinges on the exogenous break up of connections occurring when the supervisory authority places a bank under special administration, resetting its board. For these banks, we compare the dynamics of loans to firms that lost the connection with those of the unconnected firms, chosen through propensity score matching among borrowers from the same banks. We find that the loss of connection is associated with a significant and large drop in the firms’ granted loans, and, in particular, in the credit lines that can be unilaterally modified by the lender in the short term. We also show that the advantages of the connection are due mainly to favouritism, rather than to privileged information flows.
Group therapy via videoconferencing for individuals with early psychosis: A pilot study
Authors: Lecomte Tania , Abdel‐Baki Amal , Francoeur Audrey , Cloutier Briana , Leboeuf Amélie , Abadie Pascale , Villeneuve Marie , Guay Stephane
Published: December 2020

Aim

The COVID‐19 pandemic has introduced many mental health professionals to therapy via videoconferencing. Mostly individual teletherapy has been offered and studied, although group therapy is often offered in clinics. In fact, little is known regarding group therapy's acceptability, feasibility, and potential impact when offered via videoconferencing.

Methods

This pilot study offered group cognitive‐behavioural therapy for psychosis via videoconferencing to 14 individuals with early psychosis either living in remote areas or confined during the pandemic.

Results

The rate of consenting to the study (79%) and actual participation rates were acceptable (18.5 sessions out of 24). Although some technological obstacles were encountered, solutions offered allowed the videoconferencing group to be considered feasible for most participants and therapists. Prepost results on symptoms and self‐esteem were comparable to those of other studies using the same group treatment but in‐person. Alliance scores seemed similar as well.

Conclusions

More studies are warranted on the efficacy of group therapy via videoconferencing. This pilot study does offer promising results, suggesting that a wider range of people with early psychosis can be reached and benefit from the advantages of receiving an evidence‐based group intervention.