bluuebunny/crossref_metadata_2025 huggingface dataset:
Pairing functional connectivity with population dynamics to prioritize corridors for Southern California spotted owls
Authors: Conlisk Erin , Haeuser Emily , Flint Alan , Lewison Rebecca L. , Jennings Megan K.
Published: February 2021

Aim

Land use change, climate change, and shifts to disturbance regimes make successful wildlife management challenging, particularly when ongoing urbanization constrains habitat and movement. Preserving and maintaining landscape connectivity is a potential strategy to support wildlife responding to these stressors. Using a novel model framework, we determined the population‐level benefit of a set of identified potential corridors for spotted owl population viability.

Location

Southern California, United States.

Methods

Combining habitat suitability and dynamic metapopulation models, we compared the benefit of corridors to the Southern California spotted owl population, measured as the increase in the expected minimum abundance, both now and under a future climate. Our approach considered key corridor characteristics important to conservation decisions, namely corridor irreplaceability and local population network benefit.

Results

We identified two corridors likely to increase Southern California spotted owl expected minimum abundance under current climate conditions. At the regional scale, of the 27 corridors evaluated, one corridor was irreplaceable (i.e., no other corridors in the network could provide a similar increase in abundance when the irreplaceable corridor was removed) and one corridor was identified as redundant (i.e., remaining corridors in the network can provide some of the increases in abundance offered by the removed corridor). Both putative corridors connected two large, populous and similarly sized patches. Additionally, we identified two more corridors at the local scale. We found that, under climate change, population declines may limit the benefit of connectivity for a range‐restricted species like the spotted owl.

Main conclusions

Our analytical approach highlights important criteria for corridor identification and prioritization, namely irreplaceability versus redundancy, local versus regional benefit, and corridor impact in a changing landscape. With the capability of incorporating estimated functional connectivity into population dynamics, our modelling framework advances connectivity decision‐making for other species of conservation concern and archetypal taxa within ecological communities.
Cerebral palsy in twins and higher multiple births: a Europe‐Australia population‐based study
Authors: Sellier Elodie , Goldsmith Shona , McIntyre Sarah , Perra Oliver , Rackauskaite Gija , Badawi Nadia , Fares Asma , Smithers‐Sheedy Hayley ,   The Surveillance Of Cerebral Palsy Europe Group And The Australian Cerebral Palsy Register Group
Published: February 2021

Aim

To describe the birth prevalence, temporal trends, and clinical outcomes of twins, triplets, or quadruplets with cerebral palsy (CP).

Method

This was a cross‐sectional study using data for twins, triplets, and quadruplets with prenatally or perinatally acquired CP and pooled from the Surveillance of Cerebral Palsy in Europe network (born 1992–2009) and Australian Cerebral Palsy Register (born 1993–2009). Children were at least 4 years old at time of registration. Children born in regions with population ascertainment and available denominator data were included in prevalence calculations (n=1033 twins, 81 triplets, and 11 quadruplets). Clinical data from children registered in all participating registers were described, including 2163 twins (56% male), 187 triplets (59% male), and 20 quadruplets (45% male).

Results

The birth prevalence of CP was higher with increasing plurality (twins 6.5 per 1000 live births [95% confidence interval {CI} 6.1–6.9], triplets 17.1 [95% CI 13.6–21.2], quadruplets 50.7 [95% CI 25.6–88.9]); however, prevalence by gestational age was similar across all pluralities. Between 1992–1994 and 2007–2009, prevalence of CP among twins declined (p=0.001) but prevalence of CP among triplets did not change significantly over time (p=0.55). The distributions of Gross Motor Function Classification System, epilepsy, and impairments of intellect, vision, and hearing were similar regardless of plurality.

Interpretation

The data combined from two CP register networks indicated that triplets and quadruplets had increased risk of CP compared to twins. The higher prevalence of CP in triplets and quadruplets is due to their higher risk of preterm birth. Prevalence of CP among twins significantly declined in Europe and Australia. Clinical outcomes were similar for all multiple births.

What this study adds

The overall prevalence of cerebral palsy (CP) was greater in triplets and quadruplets than twins.

The higher prevalence of CP among triplets and quadruplets was due to their higher risk of preterm birth.

Higher‐order multiples did not have more severe clinical outcomes than twins.

The prevalence of CP among twins decreased over time.
Use of dipeptidyl peptidase‐4 inhibitors and prognosis of COVID‐19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study
Authors: Roussel Ronan , Darmon Patrice , Pichelin Matthieu , Goronflot Thomas , Abouleka Yawa , Ait Bachir Leila , Allix Ingrid , Ancelle Deborah , Barraud Sara , Bordier Lyse , Carlier Aurélie , Chevalier Nicolas , Coffin‐Boutreux Christine , Cosson Emmanuel , Dorange Anne , Dupuy Olivier , Fontaine Pierre , Fremy Bénédicte , Galtier Florence , Germain Natacha , Guedj Anne‐Marie , Larger Etienne , Laugier‐Robiolle Stéphanie , Laviolle Bruno , Ludwig Lisa , Monier Arnaud , Montanier Nathanaëlle , Moulin Philippe , Moura Isabelle , Prevost Gaëtan , Reznik Yves , Sabbah Nadia , Saulnier Pierre‐Jean , Serusclat Pierre , Vatier Camille , Wargny Matthieu , Hadjadj Samy , Gourdy Pierre , Cariou Bertrand ,   for the CORONADO investigators
Published: February 2021

Aim

To investigate the association between routine use of dipeptidyl peptidase‐4 (DPP‐4) inhibitors and the severity of coronavirus disease 2019 (COVID‐19) infection in patient with type 2 diabetes in a large multicentric study.

Materials and Methods

This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID‐19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP‐4 inhibitors users vs. non‐users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW).

Results

Five hundred and ninety‐six participants were under DPP‐4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non‐users of DPP‐4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW‐adjusted models showed no significant association between the use of DPP‐4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77–1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78–1.17]). Similar neutral findings were found between use of DPP‐4 inhibitors and the risk of tracheal intubation and death.

Conclusions

These data support the safety of DPP‐4 inhibitors for diabetes management during the COVID‐19 pandemic and they should not be discontinued.
Frequency, clinical features, inflammatory cytokines and genetic background of latent autoimmune diabetes in youth in youth‐onset type 2 diabetes: Results from a nationwide, multicentre, clinic‐based, cross‐sectional study (LADA China)
Authors: Xiang Yufei , Liu Bingwen , Yun Chuan , Zhou Pengcheng , Li Xiaojue , Luo Shuoming , Xie Zhiguo , Che Zhihong , Lin Jian , Yang Lin , Li Xia , Huang Gan , Xu Aimin , Zhou Zhiguang
Published: February 2021

Aim

To investigate the frequency, clinical phenotype, inflammatory cytokine levels and genetics of glutamic acid decarboxylase autoantibody (GADA)‐positive phenotypic youth‐onset type 2 diabetes.

Materials and Methods

This nationwide, multicentre, cross‐sectional study included 5324 newly diagnosed subjects with phenotypic type 2 diabetes aged 15 years or older enrolled in the LADA China study. GADA was screened in 248 subjects with youth‐onset type 2 diabetes aged 15–29 years. Subjects who presented as GADA‐positive were defined as having latent autoimmune diabetes in youth (LADY). We added subjects with LADY, type 1 diabetes, type 2 diabetes and controls from the Diabetes Center of Central South University, and measured serum concentrations of interleukin‐6, lipocalin 2, high‐sensitivity C‐reactive protein, adiponectin and human leukocyte antigen (HLA) genotyping in subjects with LADY, age‐ and sex‐matched GADA‐negative type 2 diabetes, type 1 diabetes and controls.

Results

Twenty‐nine of the 248 subjects (11.7%) were GADA positive. Compared with subjects with type 2 diabetes, subjects with LADY were less probable to have metabolic syndrome (27.6% vs. 59.4%; p = .001). The fasting C‐peptide levels tended to be lower in subjects with LADY than in subjects with type 2 diabetes, but the difference was not statistically significant (LADY vs. type 2 diabetes: 0.21 [0.17–0.64] vs. 0.47 [0.29–0.77] nmol/L; p = .11). The cytokine levels of subjects with LADY were indistinguishable from subjects with type 1 diabetes, but subjects with LADY presented increased adiponectin levels compared with subjects with type 2 diabetes after adjusting for age, sex and body mass index (7.19 [4.05–11.66] vs. 3.42 [2.35–5.74] μg/mL; p < .05). The frequency of total susceptible HLA genotypes (DR3/3, −3/9 and −9/9) in subjects with LADY and type 1 diabetes were similarly higher than controls (LADY and type 1 diabetes vs. controls: 21.4% and 30.8% vs. 2.6%, respectively; p < .001).

Conclusions

A high GADA positivity was observed in youth‐onset type 2 diabetes subjects in China. As subjects with LADY had an increased susceptible HLA genetic load and different cytokine levels compared with subjects with type 2 diabetes, differentiating LADY from phenotypic type 2 diabetes subjects is important.
The comparative effects of intensive glucose lowering in diabetes patients aged below or above 65 years: Results from the ADVANCE trial
Authors: Ohkuma Toshiaki , Chalmers John , Cooper Mark , Hamet Pavel , Harrap Stephen , Marre Michel , Mancia Giuseppe , Poulter Neil , Woodward Mark
Published: February 2021

Aims

For relatively old patients with diabetes, current guidelines recommend adjustment of glycaemic goals based on patients' cognitive function, or coexisting chronic illnesses. However, the evidence which supports the efficacy and safety of intensive glucose lowering in older patients with diabetes is scarce. The objective of the present study was to compare the efficacy and safety of intensive glucose lowering in patients with type 2 diabetes stratified by age (<65 and ≥ 65 years), and examine whether the effects differ according to patients’ characteristics in the older patient group.

Materials and Methods

The effects of intensive glucose lowering (to a target glycated haemoglobin [HbA1c] concentration of ≤48 mmol/mol [6.5%]) on major clinical outcomes were evaluated by Cox regression models according to subgroups defined by baseline age of <65 or ≥ 65 years in the ADVANCE trial (n = 11 140).

Results

Over a median follow‐up of 5 years, intensive glucose lowering significantly decreased the risk of the composite of major macrovascular and microvascular events (hazard ratio 0.90, 95% confidence interval 0.82‐0.98), with no heterogeneity in the effects across age subgroups (p for heterogeneity = 0.44). Relative effects on all‐cause death, cardiovascular death, and components of major vascular events were also similar (P for heterogeneity ≥0.06), except for severe hypoglycaemia, which was of greater risk for patients aged <65 years. Absolute benefits and harms were broadly consistent across subgroups. Among patients aged ≥65 years, randomized treatment effects did not differ significantly across different levels of cognitive function or coexisting chronic illnesses.

Conclusions

Our results suggest that an intensive glycaemic control strategy to reduce HbA1c to 48 mmol/mol (6.5%) provided broadly similar benefits and harms and may be recommended for older, as well as younger, patients.
Rates and estimated cost of primary care consultations in people diagnosed with type 2 diabetes and comorbidities: A retrospective analysis of 8.9 million consultations
Authors: Coles Briana , Zaccardi Francesco , Seidu Sam , Gillies Clare L. , Davies Melanie J. , Hvid Christian , Khunti Kamlesh
Published: February 2021

Aims

To determine whether telephone and face‐to‐face primary care consultation rates, costs, and temporal trends during 2000 to 2018 differed by the number of comorbidities in people with type 2 diabetes (T2DM).

Methods

A total of 120 409 adults with newly diagnosed T2DM between 2000 and 2018 were classified by the number of prevalent and incident comorbidities. Data on face‐to‐face and telephone primary care consultations with a nurse or physician were obtained. Crude and sex‐ and age‐adjusted annual consultation rates and associated costs were calculated based on the number of comorbidities at the time of consultation.

Results

The crude rate of face‐to‐face primary care consultations for patients without comorbidities was 10.3 (95% confidence interval [CI] 10.3‐10.4) per person‐year, 12.7 (95% CI 12.7‐12.7) for patients with one comorbidity, 15.1 (95% CI 15.1‐15.2) for those with two comorbidities, and 18.7 (95% CI 18.7‐18.8) for those with three or more comorbidities. The mean annual inflation‐adjusted cost for face‐to‐face consultations was £412.70 per patient without comorbidities, £516.80 for one comorbidity, £620.75 for two comorbidities, and £778.83 for three or more comorbidities. The age‐ and sex‐adjusted face‐to‐face consultation rate changed by an average of −3.3% (95% CI −4.4 to −2.3) per year from 2000 to 2018 for patients without comorbidities, −2.7% (95% CI −4.0 to −1.3) for those with one comorbidity, −2.2% (95% CI −3.3 to −1.2) for those with two comorbidities, and −4.3% (95% CI −8.7 to +0.3) for those with three or more comorbidities.

Conclusions

Although consultation rates for all patients decreased from 2000 to 2018, there was a significant disparity between the rate for patients with and without comorbidities. Patients with T2DM and comorbidities may require different models of service delivery.
Poverty volatility and poverty in developing countries
Authors: Gnangnon Sena Kimm
Published: February 2021

This article examines the effect of poverty volatility on poverty in developing countries. Poverty volatility refers to the amplitude of the change in poverty rates over a given period of time. Variations in poverty rates can potentially arise from countries' vulnerability to a variety of shocks that induce greater macroeconomic volatility, including economic growth volatility. The empirical analysis shows that poverty volatility consistently induces a rise in poverty rates, and this positive poverty effect of poverty volatility increases as the degree of poverty volatility rises. Policies that help reduce poverty volatility (including by dampening economic growth volatility) would contribute to poverty reduction.
Do enlarged fiscal deficits cause inflation? The historical record
Authors: Bordo Michael D. , Levy Mickey D.
Published: February 2021

We survey the historical record for two centuries on the connection between expansionary fiscal policy and inflation. The relationship holds in wartime when fiscally stressed governments resorted to the inflation tax. In two peacetime episodes in the early twentieth century, bond‐financed fiscal deficits, unbacked by future taxes, may have contributed to inflation. Fiscal influence on monetary policy was important in the Great Inflation 1965–1983. Expansionary monetary and fiscal policy did not lead to inflation in the Global Financial Crisis of 2007–08 but, by contrast, the fiscal and monetary response to the COVID‐19 pandemic may involve risks of fiscal dominance and future inflation.
International free riding on institutions
Authors: Gmeiner Robert
Published: February 2021

Economic institutions are linked to economic growth because they create conditions favourable for production and exchange. Institutions can give a country comparative advantage in producing some goods. If its trading partners lack such institutions, it can still enjoy their benefits by importing these goods. Some institutions, such as intellectual property rights, have non‐excludable benefits because the resulting production is intangible, non‐rival, and often publicly disclosed. The profits, or surplus, that result, however, is rival. Foreign countries can ‘free ride’ on this benefit by misappropriating rival surplus through infringement. This article develops a theory of institutional free riding in which firms in one country free ride on the benefit of foreign institutions to the detriment of their competitor firms and their countries' institutions. It evaluates the incentives of firms and governments for this free riding, its effects, and potential responses to mitigate these effects.
Impact of the Affordable Care Act on diabetes diagnoses in the United States: A county‐level analysis
Authors: Palanki Rupa , Chamarthy Siva , Palanki Srinivas
Published: February 2021

Our research examines whether there is a causal effect between expanding health insurance and diabetes incidence. Comprehensive county‐level data from the United States is used to study the effect of Medicaid expansion on diabetes rates. The analysis is based on cross‐county variation according to Affordable Care Act health care reforms, along with county share‐eligibility variation. Difference‐in‐difference and triple‐difference statistical regression specifications are employed to control for confounding variables. The results suggest a slight negative relationship between expanding health insurance and diabetes diagnoses.
Population structure of whitefly (Bemisia tabaci) and the link between vector dynamics and seasonal incidence of yellow mosaic disease in blackgram (Vigna mungo)
Authors: Kamesh Krishnamoorthy Kalyankumar , Malathi Varagur Ganesan , Renukadevi Perumal , Mohan Kumar Subbarayalu , Raveendran Muthurajan , Manivannan Narayana , Rajendran Lingan , Karthikeyan Gandhi
Published: February 2021

The hemipteran pest silverleaf whitefly, Bemisia tabaci (Gennadius) (Aleyrodidae), is of high economic importance, as it infests a wide range of agricultural and horticultural crops. The pest is regarded as a cryptic species complex. In the present study, the cryptic species composition and viruliferous status of B. tabaci in association with yellow mosaic disease (YMD), caused by Mungbean yellow mosaic virus (MYMV), in blackgram [Vigna mungo (L.) Hepper (Fabaceae)], were assessed over three cropping seasons, viz., Rabi, summer, and Kharif, at three locations in Tamil Nadu, India. This study identified three cryptic B. tabaci species: (1) Asia I, (2) Asia II‐5, and (3) Asia II‐8. Asia II‐8 was the dominant species in all three seasons across locations. Despite the absence of YMD symptoms in many plants, up to 73% of whiteflies sampled from YMD‐resistant and susceptible blackgram cultivars were MYMV‐viruliferous. This suggests that the YMD incidence of blackgram does not directly associate with viruliferous whitefly populations in the field.
Greater preference for eveningness is associated with negative symptoms in an ultra‐high risk for psychosis sample
Authors: Shetty Jashmina J. , Nicholas Christian , Nelson Barnaby , McGorry Patrick D. , Lavoie Suzie , Markulev Connie , Schäfer Miriam R. , Thompson Andrew , Yuen Hok Pan , Yung Alison R. , Nieman Dorien H. , de Haan Lieuwe , Amminger G. Paul , Hartmann Jessica A.
Published: February 2021

Aim

Investigating biological processes in at‐risk individuals may help elucidate the aetiological mechanisms underlying psychosis development, refine prediction models and improve intervention strategies. This study examined the associations between sleep disturbances, chronotype, depressive and psychotic symptoms in individuals at ultra‐high risk for psychosis.

Methods

A sample of 81 ultra‐high risk patients completed clinical interviews and self‐report assessments of chronotype and sleep during the Neurapro clinical trial. Mixed regression was used to investigate the cross‐sectional associations between symptoms and sleep disturbances/chronotype.

Results

Sleep disturbances were significantly associated with increased depressive and attenuated positive psychotic symptoms. Greater preference for eveningness was significantly associated with increased negative symptoms, but not with depressive or attenuated positive psychotic symptoms.

Conclusion

Sleep disturbances and chronotype may impact the emerging psychopathology experienced by ultra‐high risk individuals. Further, the preliminary relationship observed between greater preference for eveningness and negative symptoms offers a unique opportunity to treat negative symptoms through chronobiological approaches.
Forced swim stressor: Trends in usage and mechanistic consideration
Authors: Molendijk Marc L. , de Kloet E. Ronald
Published: February 2021

The acquired immobility response during the “forced swim test (FST)” is not a rodent model of depression, but the test has some validity in predicting a compound's antidepressant potential. Nevertheless, 60% of the about 600 papers that were published annually the past 2 years label the rodent's immobility response as depression‐like behaviour, but the relative contribution per country is changing. When the Editors‐in‐Chief of 5 journals publishing most FST papers were asked for their point of view on labelling immobility as depression‐like behaviour and despair, they responded that they primarily rely on the reviewers regarding scientific merit of the submission. One Editor informs authors of the recent NIMH notice (https://grants.nih.gov/grants/guide/notice‐files/NOT‐MH‐19‐053.html) which encourages investigators to use animal models “for” addressing neurobiological questions rather than as model “of” specific mental disorders. The neurobiological questions raised by use of the FST fall in two categories. First, research on the role of endocrine and metabolic factors, with roots in the 1980s, and with focus on the bottom‐up action of glucocorticoids on circuits processing salient information, executive control and memory consolidation. Second, recent findings using novel technological and computational advances that have allowed great progress in charting top‐down control in the switch from active to passive coping with the inescapable stressor executed by neuronal ensembles of the medial prefrontal cortex via the peri‐aquaductal grey. It is expected that combining neural top‐down and endocrine bottom‐up approaches will provide new insights in the role of stress‐coping and adaptation in pathogenesis of mental disorders.
Primary motor cortex excitability as a marker of plasticity in a stimulation protocol combining action observation and kinesthetic illusion of movement
Authors: Bisio Ambra , Biggio Monica , Canepa Patrizio , Faelli Emanuela , Ruggeri Piero , Avanzino Laura , Bove Marco
Published: February 2021

Action observation combined with proprioceptive stimulation able to induce a kinesthetic illusion of movement (AO‐KI) was shown to elicit a plastic increase in primary motor cortex (M1) excitability, with promising applications in rehabilitative interventions. Nevertheless, the known individual variability in response to combined stimulation protocols limits its application. The aim of this study was to examine whether a relationship exists between changes in M1 excitability during AO‐KI and the long‐lasting changes in M1 induced by AO‐KI. Fifteen volunteers received a conditioning protocol consisting in watching a video showing a thumb‐opposition movement and a simultaneous proprioceptive stimulation that evoked an illusory kinesthetic experience of their thumbs closing. M1 excitability was evaluated by means of single‐pulse transcranial magnetic stimulation before, DURING the conditioning protocol, and up to 60 min AFTER it was administered. M1 excitability significantly increased during AO‐KI with respect to a rest condition. Furthermore, AO‐KI induced a long‐lasting increase in M1 excitability up to 60 min after administration. Finally, a significant positive correlation appeared between M1 excitability changes during and after AO‐KI; that is, participants who were more responsive during AO‐KI showed greater motor cortical activity changes after it. These findings suggest that M1 response during AO‐KI can be considered a neurophysiological marker of individual responsiveness to the combined stimulation since it was predictive of its efficacy in inducing long‐lasting M1 increase excitability. This information would allow knowing in advance whether an individual will be a responder to AO‐KI.
Relative efficacy and stability of biological and synthetic nitrification inhibitors in a highly nitrifying soil: Evidence of apparent nitrification inhibition by linoleic acid and linolenic acid
Authors: Ma Yan , Jones Davey L. , Wang Jinyang , Cardenas Laura M. , Chadwick David R.
Published: February 2021

Biological nitrification inhibition is a plant‐mediated rhizosphere process where natural nitrification inhibitors can be produced and released by roots to suppress nitrifier activity in soil. Nitrification is one of the critical soil processes in the nitrogen (N) cycle, but unrestricted and rapid nitrification in agricultural systems can result in major losses of N from the plant–soil system (i.e., by NO3− leaching and gaseous N emissions). In this study, we explored the potential efficacy of biological nitrification inhibitors (linoleic acid [LA] and linolenic acid [LN]) and a proven efficient synthetic (dicyandiamide [DCD]) nitrification inhibitor on N dynamics, nitrous oxide (N2O) and carbon dioxide (CO2) emissions in a highly nitrifying soil. 14C‐labelled LA, LN and DCD mineralization was determined in a parallel experiment to explore the fate of inhibitors after application. We found that LA and LN had no effect on soil NH4+ concentrations, but significantly decreased NO3− concentrations. Soil that received DCD had lower NO3− and higher NH4+ concentrations than the control (soil without nitrification inhibitors). LA and LN increased the cumulative N2O and CO2 emissions when they were applied at high concentrations (635 or 1,270 mg kg−1 dry soil). LA and LN had a much greater mineralization rate than that of DCD: 47–56%, 37–61% and 2.7–5.5%, respectively, after 38 days incubation. We conclude that in contrast to the direct inhibition of nitrification caused by DCD, addition of LA and LN may cause apparent nitrification inhibition by promoting microbial immobilization of soil NH4+ and/or NO3−. Future studies on nitrification inhibitors need to clearly differentiate between the direct and indirect effects that result from addition of these compounds to soil.

Highlights

The efficacy and stability of nitrification inhibitors in a highly nitrifying soil were explored.

This study supports efforts to mitigate N losses and improve nitrogen use efficiency of inputs.

Addition of LA, LN and DCD can decrease NO3− concentration, but their modes of action may be different.

The apparent effect of LA and LN on soil NO3− concentration could be indirect.
Can Big Data guide prognosis and clinical decisions in epilepsy?
Authors: Li Xiaojin , Cui Licong , Zhang Guo‐Qiang , Lhatoo Samden D.
Published: February 2021

Big Data is no longer a novel concept in health care. Its promise of positive impact is not only undiminished, but daily enhanced by seemingly endless possibilities. Epilepsy is a disorder with wide heterogeneity in both clinical and research domains, and thus lends itself to Big Data concepts and techniques. It is therefore inevitable that Big Data will enable multimodal research, integrating various aspects of “‐omics” domains, such as phenome, genome, microbiome, metabolome, and proteome. This scope and granularity have the potential to change our understanding of prognosis and mortality in epilepsy. The scale of new discovery is unprecedented due to the possibilities promised by advances in machine learning, in particular deep learning. The subsequent possibilities of personalized patient care through clinical decision support systems that are evidence‐based, adaptive, and iterative seem to be within reach. A major objective is not only to inform decision‐making, but also to reduce uncertainty in outcomes. Although the adoption of electronic health record (EHR) systems is near universal in the United States, for example, advanced clinical decision support in or ancillary to EHRs remains sporadic. In this review, we discuss the role of Big Data in the development of clinical decision support systems for epilepsy care, prognostication, and discovery.
Everolimus in adult tuberous sclerosis complex patients with epilepsy: Too late for success? A retrospective study
Authors: Stockinger Jakob , Strzelczyk Adam , Nemecek Andrea , Cicanic Michal , Bösebeck Frank , Brandt Christian , Hamer Hajo , Intravooth Tassanai , Steinhoff Bernhard J.
Published: February 2021

Objective

There is evidence that everolimus (EVE) significantly reduces seizure frequency in epilepsy patients with tuberous sclerosis complex (TSC). Given that TSC‐related proliferative processes are more dynamic during brain development, seizure outcomes of patients treated with EVE may be age‐related and may be less convincing in adult patients. The aim of this study was to assess the effectiveness and the safety profile of EVE in adults in clinical practice.

Methods

We performed a multicenter retrospective chart review of TSC subjects with active epilepsy who started EVE in adulthood (≥18 years of age) at seven German epilepsy centers. The primary endpoint was the retention rate after 6 months.

Results

A total of 45 subjects with a mean age of 31.6 ± 11.1 years at EVE start fulfilled the inclusion criteria. Retention rate after 6 months was 98% (43/44 evaluable subjects). Response rate (seizure reduction ≥ 50%) was 33% (14/43 evaluable subjects; four completely seizure‐free). We did not find a significant relationship between epilepsy outcome parameters and patient age at EVE start. Adverse events were reported in 19 subjects and were judged to be serious in six patients. Three patients died during the observation period.

Significance

Evidence suggests that EVE is an effective add‐on treatment for epilepsy in adult TSC patients, surprisingly without any age limit to individual benefit. A strong age‐dependent effect within the period of adulthood seems unlikely. Even if there was no proof of a causal relationship between deaths and EVE intake, patients with EVE should be carefully monitored, especially for infections and stomatitis.
Phenobarbital, midazolam, bumetanide, and neonatal seizures: The devil is in the details
Authors: Ben‐Ari Yehezkel , Delpire Eric
Published: February 2021

Kaila, Löscher, and colleagues report that phenobarbital (PHB) and midazolam (MDZ) attenuate neonatal seizures following birth asphyxia, but the former only when applied before asphyxia and the latter before or after the triggering insult. In contrast, the NKCC1 chloride importer antagonist bumetanide (BUM) had no effect whether applied alone or with PHB. The observations are compelling and in accord with earlier studies. However, there are several general issues that deserve discussion. What is the clinical relevance of these data and the validity of animal models of encephalopathic seizures? Why is it that although they act on similar targets, these agents have different efficacy? Are both PHB and MDZ actions restricted to γ‐aminobutyric acidergic (GABAergic) mechanisms? Why is BUM inefficient in attenuating seizures but capable of reducing the severity of other brain disorders? We suggest that the relative failure of antiepileptic drugs (AEDs) to treat this severe life‐threatening condition is in part explicable by the recurrent seizures that shift the polarity of GABA, thereby counteracting their effects on their target. AEDs might be efficient after a few seizures but not recurrent ones. In addition, PHB and MDZ actions are not limited to GABA signals. BUM efficiently attenuates autism symptomatology notably in patients with tuberous sclerosis but does not reduce the recurrent seizures, illustrating the uniqueness of epilepsies. Therefore, the efficacy of AEDs to treat babies with encephalopathic seizures will depend on the history and severity of the seizures prior to their administration, challenging a universal common underlying mechanism.
Big data analytics on patents for innovation public policies
Authors: Sousa Maria José , Jamil George , Walter Cicero Eduardo , Au‐Yong‐Oliveira Manuel , Moreira Fernando
Published: February 2021

This study seeks to answer the following research question: “What factors can explain the number of patent filing requests made by residents in Brazil at patent offices in Brazil, the United States, Europe, and triadic patent families?”. The methods used in this research are quantitative, using big data from private and public investments in Science and Technology, and about patent deposit numbers in Brazil from 2000 to 2017. A model of linear regression was performed and explains how these investments in Science and Technology influence patent deposit numbers. The results of this research study point towards the importance of universities, up and beyond the traditional training and education aspect of university activity. The importance of public and private innovation investments is also shown to be important. This study shows that the patent registrations in the different regions under analysis are affected by different factors. There is thus no single formula towards the creation of innovation output and governments would do well to continue to invest in higher education while also investing in public research and development activities. Additionally, and not least important, private entities should be continually encouraged to make innovation investments and favourable government policies need to thus exist for this to happen. Finally, the low numbers regarding patent filings in Brazil may be linked to institutional deficiencies in the country. Patent breaches may be difficult to punish, and the judicial system may be slow and untrustworthy, compared to the United States and to Europe—leading to diminished patent registrations in Brazil. A set of implications and recommendations for policy derived from this study and will be strategic for policymakers.
How do charity regulators build public trust?
Authors: Yang Cherrie , Northcott Deryl
Published: February 2021

Public trust serves as an important foundation for the charity sector, but has been diminishing in many countries. Charity regulation exists to promote public trust in charities, but we know little about how it is implemented by regulators to build public trust. This research examines regulators’ efforts to build public trust in charities by promoting and implementing regulation that increases accountability and transparency requirements. A legal perspective on regulation and trust (Colombo, 2010) is combined with institutional work theory (Lawrence & Suddaby, 2006) to analyse interviews with New Zealand charity regulators and standard setters. The findings detail regulators’ reflexive trust‐building processes and practices and reveal a complex and challenging trust‐building dynamic among regulators, charities and the general public. Regulators’ efforts are revealed to demonstrate a ‘hybrid’ approach to regulation as they expand beyond policing charities’ regulatory compliance, educating charities on how to improve their public accountability and investigating public concerns about charity wrongdoing to also engage in proactive modes of trust‐building that directly target the public. Based on these findings, implications are suggested for regulators in other jurisdictions who seek to build public trust in charities.
Living Under the Shadows: Experiences of Latino Immigrant Families at Risk for Deportation
Authors: Rayburn Allison D. , McWey Lenore M. , Gonzales‐Backen Melinda A.
Published: February 2021

Objective

The aim of this study was to examine the experiences of Latino youth and their parents who are at risk for detainment or deportation to gain an in‐depth understanding of the impact of the risk for parental deportation on psychosocial well‐being.

Background

Children born in the United States to foreign‐born parents comprise approximately 27% of the U.S. population. Approximately 5.7 million U.S.‐born children live with parents without legal residency documentation, and nearly 500,000 children had at least one parent detained or deported over a 2‐year period. There is a high risk for negative child and family outcomes associated with parental deportation.

Method

A constructivist grounded theory design was used to complete semistructured interviews with families (N = 16) at risk for parental deportation. A quantitative trauma assessment was used to triangulate qualitative findings.

Results

Results indicated four core themes: (a) parents and youth experience emotional distress associated with the risk of deportation, (b) parents and youth experience injustices associated with the threat of deportation, (c) children experience their freedoms as conditional, and (d) children suffer.

Conclusions

Concepts from ambiguous loss and developmental trauma may aid our understanding of family emotional distress associated with the risk for deportation and improve family services aimed to promote family well‐being.

Implications

Family scholar‐advocate and scholar‐activist approaches, in which we use our positions of privilege to educate others about the needs of underserved families, may be helpful for families at‐risk for deportation.
Parenting Practices and Child Conduct Problems in a Norwegian Subclinical Sample: Variable and Person‐Centered Approaches
Authors: Hukkelberg Silje S. , Ogden Terje
Published: February 2021

Objective

The aims of this study were (a) to examine how different parenting practices connect to each other and to child conduct problems (variable‐centered approach) and (b) to identify groups of parents who share the same parenting style and identify how these relate to child conduct problems (person‐centered approach).

Background

Substantial evidence indicates that positive parenting practices are associated with lower levels of child conduct problems, whereas negative practices are associated with higher levels of child problem behavior. Research is limited when it comes to examining parenting practices at intake to parent management training in clinical Scandinavian samples.

Method

Participants were 551 Norwegian parents and their children (aged 3–12 years) with moderate to high levels of conduct problems. Parents reported on child conduct problems and parenting practices. Associations between different parenting practices and child conduct problems were examined using network and latent profile analyses.

Results

Three latent profiles of parenting were identified, each related to different levels of child conduct problems. The network of practices showed that parental mental distress and harsh discipline were directly associated with higher levels of child conduct problems. The majority of parents were characterized as permissive and displayed a mix of positive and harsh parenting.

Conclusion

Harsh parenting was related to higher levels of child conduct problems. Discipline skills appeared as especially important in the network analyses.

Implications

Parent training should address harsh discipline practices and parental mental distress, given that these are associated with more child conduct problems. Discipline skills appeared as the most important targets for changing overall parenting practices.
Clinical advances in targeting epigenetics for cancer therapy
Authors: Feng Shengrui , De Carvalho Daniel D.
Published: February 2021

The appropriate coordination between epigenetic regulators is essential for spatial and temporal regulation of gene expression and maintenance of cell identity. Cancer is a disease driven by both genetic and epigenetic alterations. The widespread dysregulation and reversible nature of epigenetic alterations confer cancer cells with vulnerabilities for therapeutic interventions. Over the past decades, remarkable progress has been made in developing drugs that target epigenetic regulators, with many drugs under evaluation in clinical trials. Here, we summarize the epigenetic drugs currently in clinical investigations and highlight the potentials and challenges in their implication to treat cancer. We also discuss the preclinical and clinical results of combination therapies with epigenetic drugs and other therapies such as targeted and immune‐based therapies.
A glaucoma‐ and ALS‐associated mutant of OPTN induces neuronal cell death dependent on Tbk1 activity, autophagy and ER stress
Authors: Medchalmi Swetha , Tare Priyanka , Sayyad Zuberwasim , Swarup Ghanshyam
Published: February 2021

Mutations in OPTN are associated with glaucoma, an eye disease, and also with amyotrophic lateral sclerosis (ALS), a motor neuron disease. A 2‐bp insertion in OPTN (691_692insAG or 2bpIns‐OPTN) is associated with both glaucoma and ALS. This mutation results in frame shift after 127 amino acids, giving rise to a protein with C‐terminal aberrant sequence. We have explored the mechanism of induction of cell death by this mutant in a motor neuron cell line, NSC‐34, and also in a retinal cell line, 661W. Compared to wild‐type OPTN, this mutant induced more cell death in NSC‐34 and 661W cells. This mutant localizes predominantly in the nucleus whereas normal OPTN localizes in the cytoplasm. Deletion analysis of 2bpIns‐OPTN showed that the aberrant sequence was not essential for cell death induction. This mutant interacts with TANK‐binding kinase 1 (Tbk1) but not with OPTN and activates Tbk1. This mutant induced ER stress in NSC‐34 cells as seen by induction of C/EBP homologous protein (CHOP) and some other genes. Induction of CHOP, autophagosomal protein LC3‐II and cell death by this mutant were abrogated by Tbk1 knockdown and also by 4‐phenylbutyric acid, that inhibits ER stress. Induction of CHOP and cell death by 2bpIns‐OPTN was autophagy dependent as shown by the effect of Atg5 knockdown. This mutant caused increased formation of LC3‐positive aggregates. Treatment of cells with autophagy inducer rapamycin reduced LC3‐positive aggregates, CHOP and cell death induced by 2bpIns‐OPTN. These results suggest that constitutive activation of Tbk1 by 2bpIns‐OPTN leads to impaired autophagy that results in ER stress and cell death.
Fatigue of X65 steel in the sour corrosive environment—A novel experimentation and analysis method for predicting fatigue crack initiation life from corrosion pits
Authors: Farhad Farnoosh , Smyth‐Boyle David , Zhang Xiang
Published: February 2021

Oil and gas pipelines manufactured from API‐5L Grade X65 steel are generally subjected to cyclic loading and their internal surfaces are frequently exposed to corrosive sour fluids. Exposure of pipelines to these environments often leads to localized corrosion (pitting) and decreased fatigue life. Corrosion pits are geometrical discontinuities that may promote fatigue cracking by acting as stress raisers. In order to optimize asset inspection and repair scheduling, it is important to understand the fatigue behavior of X65 steel and in particular, the ability to predict the crack initiation from corrosion pit. To achieve this level of understanding, conducting fatigue tests in an environmental condition replicating the field environment is important. This paper presents the test protocol and results of environmental fatigue testing using bespoke laboratory apparatus to undertake in situ corrosion fatigue tests in a sour corrosive environment under uniaxial loading. The environment selected represent processes that are likely to occur at internal surfaces of oil and gas pipelines exposed to production fluids. The tests were carried out on smooth samples to obtain S‐N curve in this specific environment as well as on pre‐pitted samples. An electrochemical method is used to create corrosion pits on the samples. Also, a model is proposed to predict the crack initiation life from corrosion pit, using a local stress‐based technique, which has been validated by experimental test results. Post‐test fractography was carried out by scanning electron microscopy (SEM). The performance of our approach is demonstrated. The innovation is anticipated to encourage other workers to employ similar small‐scale tests requiring toxic and challenging test environments.
Fatigue of short‐natural‐fiber‐reinforced high‐density polyethylene: Stochastic modeling of single‐gear‐tooth bending
Authors: Blais Philippe , Toubal Lotfi
Published: February 2021

A Markov chain model was compared to experimental data in the testing of a natural‐fiber‐reinforced composite material proposed for low‐torque gearing applications. The material is tested on a single gear tooth bench to assess multiple damage measurement methods. The model was coupled to three indices of single gear tooth damage: cracking monitored with a high resolution camera, residual load measured with the fatigue machine load cell, and acoustic emission detected by piezoelectric sensors. The model has predictive skill and contributed to better understanding of how damage to the material evolved during the fatigue tests.
Adaptive responses of free‐living and symbiotic microalgae to simulated future ocean conditions
Authors: Chan Wing Yan , Oakeshott John G. , Buerger Patrick , Edwards Owain R. , van Oppen Madeleine J. H.
Published: February 2021

Marine microalgae are a diverse group of microscopic eukaryotic and prokaryotic organisms capable of photosynthesis. They are important primary producers and carbon sinks but their physiology and persistence are severely affected by global climate change. Powerful experimental evolution technologies are being used to examine the potential of microalgae to respond adaptively to current and predicted future conditions, as well as to develop resources to facilitate species conservation and restoration of ecosystem functions. This review synthesizes findings and insights from experimental evolution studies of marine microalgae in response to elevated temperature and/or pCO2. Adaptation to these environmental conditions has been observed in many studies of marine dinoflagellates, diatoms and coccolithophores. An enhancement in traits such as growth and photo‐physiological performance and an increase in upper thermal limit have been shown to be possible, although the extent and rate of change differ between microalgal taxa. Studies employing multiple monoclonal replicates showed variation in responses among replicates and revealed the stochasticity of mutations. The work to date is already providing valuable information on species’ climate sensitivity or resilience to managers and policymakers but extrapolating these insights to ecosystem‐ and community‐level impacts continues to be a challenge. We recommend future work should include in situ experiments, diurnal and seasonal fluctuations, multiple drivers and multiple starting genotypes. Fitness trade‐offs, stable versus plastic responses and the genetic bases of the changes also need investigating, and the incorporation of genome resequencing into experimental designs will be invaluable.