bluuebunny/crossref_metadata_2025 huggingface dataset:
Migrants’ remittances and economic growth in Egypt: an empirical analysis from 1980 to 2017
Authors: Qutb Rasha
Published: March 2021

Purpose

Migrants’ remittances to Egypt have increased considerably in both size and importance over the past 40 years. This increase has made Egypt one of the top remittance recipients in the world and the leading recipient country in the Middle East. As migrant remittances are one of Egypt's main sources of foreign capital, this study aims to identify the impact of these remittances on economic growth.

Design/methodology/approach

The study collects annual data on migrant remittances sent to Egypt during the period 1980–2017. The study uses the Augmented Dickey–Fuller test and Johnsen's Co-integration test to establish long-run relationships between variables. Then, a vector error correction model (VECM) is used to combine long-run and short-run dynamics, and a Granger causality test is performed. Finally, diagnostic tests of the VECM are conducted.

Findings

Results reveal that migrants’ remittances to Egypt are countercyclical in the sense that they have a long-term negative impact on economic growth. These results are determined by the Granger causality between migrants' remittances, inflation rate and imports.

Practical implications

The study can help policymakers to develop appropriate policies to turn migrants' remittances into a reliable source of capital that could result in a stable economic growth.

Originality/value

Although various empirical studies have examined the growth effect of remittances, most of them are based on cross-country data. This study contributes to the field by attempting to close a gap in the literature by empirically analyzing the impact of remittances on a single country over a long period.
Analytical models to estimate the structural behaviour of fused deposition modelling components
Authors: Cerda-Avila Steffany N. , Medellín-Castillo Hugo I. , Lim Theodore
Published: March 2021

Purpose

The purpose of this study is to evaluate the capability and performance of analytical models to predict the structural mechanical behaviour of parts fabricated by fused deposition modelling (FDM).

Design/methodology/approach

A total of eight existing and newly proposed analytical models, tailored to satisfy the structural behaviour of FDM parts, are evaluated in terms of their capability to predict the ultimate tensile stress (UTS) and the elastic modulus (E) of parts made of polylactic acid (PLA) by the FDM process. This evaluation is made by comparing the structural properties predicted by these models with the experimental results obtained from tensile tests on FDM specimens fabricated with variable infill percentage, perimeter layers and build orientation.

Findings

Some analytical models are able to predict with high accuracy (prediction errors smaller than 5%) the structural behaviour of FDM and categories of similar additive manufactured parts. The most accurate model is Gibson’s and Ashby, followed by the efficiency model and the two new proposed exponential and variant Duckworth models.

Research limitations/implications

The study has been limited to uniaxial loading conditions along three different build orientations.

Practical implications

The structural properties of FDM parts can be predicted by analytical models based on the process parameters and material properties. Product engineers can use these models during the design for the additive manufacturing process.

Originality/value

Existing methods to estimate the structural properties of FDM parts are based on experimental tests; however, such methods are time-consuming and costly. In this work, the use of analytical models to predict the structural properties of FDM parts is proposed and evaluated.
Invertebrate functional traits and terrestrial nutrient cycling: Insights from a global meta‐analysis
Authors: McCary Matthew A. , Schmitz Oswald J.
Published: March 2021

Functional traits are useful for characterizing variation in community and ecosystem dynamics. Most advances in trait‐based ecology to date centre on plant functional traits, although there is an increasing recognition that animal traits are also key contributors to processes operating at the community or ecosystem scale.

Terrestrial invertebrates are incredibly diverse and ubiquitous animals with important roles in nutrient cycling. Despite their widespread influence on ecosystem processes, we currently lack a synthetic understanding of how invertebrate functional traits affect terrestrial nutrient cycling.

We present a meta‐analysis of 511 paired observations from 122 papers that examined how invertebrate functional traits affected litter decomposition rates, nitrogen pools and litter C:N ratios. Based on the available data, we specifically assessed the effects of feeding mode (bioturbation, detritus shredding, detritus grazing, leaf chewing, leaf piercing, ambush predators, active hunting predators) and body size (macro‐ and micro‐invertebrates) on nutrient cycling.

The effects of invertebrates on terrestrial nutrient cycling varied according to functional trait. The inclusion of both macro‐ (≥2 mm) and micro‐invertebrates (<2 mm) increased litter decomposition by 20% and 19%, respectively. All detritivorous feeding modes enhanced litter decomposition rates, with bioturbators, detritus shredders and detritus grazers increasing decomposition by 28%, 22% and 15%, respectively. Neither herbivore feeding mode (e.g. leaf chewers and leaf piercers) nor predator hunting mode (ambush and active hunting) affected decomposition. We also revealed that bioturbators and detritus grazers increased soil nitrogen availability by 99% and 70%, respectively, and that leaf‐chewing herbivores had a weak effect on litterfall stoichiometry via reducing C:N ratios by 11%.

Although functional traits might be useful predictors of ecosystem processes, our findings suggest context‐dependent effects of invertebrate traits on terrestrial nutrient cycling. Detritivore functional traits (i.e. bioturbators, detritus shredders and detritus grazers) are more consistent with increased rates of nutrient cycling, whereas our currently characterized predator and herbivore traits are less predictive. Future research is needed to identify, standardize and deliberately study the impacts of invertebrate functional traits on nutrient cycling in hopes of revealing the key functional traits governing ecosystem functioning worldwide.
Online and face‐to‐face learning: Evidence from students’ performance during the Covid‐19 pandemic
Authors: Chisadza Carolyn , Clance Matthew , Mthembu Thulani , Nicholls Nicky , Yitbarek Eleni
Published: March 2021

This study investigates the factors that predict students' performance after transitioning from face‐to‐face to online learning as a result of the Covid‐19 pandemic. It uses students' responses from survey questions and the difference in the average assessment grades between pre‐lockdown and post‐lockdown at a South African university. We find that students' performance was positively associated with good wifi access, relative to using mobile internet data. We also observe lower academic performance for students who found transitioning to online difficult and who expressed a preference for self‐study (i.e. reading through class slides and notes) over assisted study (i.e. joining live lectures or watching recorded lectures). The findings suggest that improving digital infrastructure and reducing the cost of internet access may be necessary for mitigating the impact of the Covid‐19 pandemic on education outcomes.
The Commercial Determinants of Three Contemporary National Crises: How Corporate Practices Intersect With the COVID‐19 Pandemic, Economic Downturn, and Racial Inequity
Authors: MAANI NASON , VAN SCHALKWYK MAY CI , PETTICREW MARK , GALEA SANDRO
Published: March 2021

Policy Points

 The United States finds itself in the middle of an unprecedented combination of crises: a global pandemic, economic crisis, and unprecedented civic responses to structural racism.

 While public sector responses to these crises have faced much justified criticism, the commercial determinants of these crises have not been sufficiently examined.

 In this commentary we examine the nature of the contributions of such actors to the conditions that underpin these crises in the United States through their market and nonmarket activities.

 On the basis of this analysis, we make recommendations on the role of governance and civil society in relation to such commercial actors in a post‐COVID‐19 world.
Reducing administrative costs in US health care: Assessing single payer and its alternatives
Authors: Scheinker David , Richman Barak D. , Milstein Arnold , Schulman Kevin A.
Published: March 2021

Objective

Excess administrative costs in the US health care system are routinely referenced as a justification for comprehensive reform. While there is agreement that these costs are too high, there is little understanding of what generates administrative costs and what policy options might mitigate them.

Data Sources

Literature review and national utilization and expenditure data.

Study Design

We developed a simulation model of physician billing and insurance‐related (BIR) costs to estimate how certain policy reforms would generate savings. Our model is based on structural elements of the payment process in the United States and considers each provider's number of health plan contracts, the number of features in each health plan, the clinical and nonclinical processes required to submit a bill for payment, and the compliance costs associated with medical billing.

Data Extraction

For several types of visits, we estimated fixed and variable costs of the billing process. We used the model to estimate the BIR costs at a national level under a variety of policy scenarios, including variations of a single payer “Medicare‐for‐All” model that extends fee‐for‐service Medicare to the entire population and policy efforts to reduce administrative costs in a multi‐payer model. We conducted sensitivity analyses of a wide variety of model parameters.

Principal Findings

Our model estimates that national BIR costs are reduced between 33% and 53% in Medicare‐for‐All style single‐payer models and between 27% and 63% in various multi‐payer models. Under a wide range of assumptions and sensitivity analyses, standardizing contracts generates larger savings with less variance than savings from single‐payer strategies.

Conclusion

Although moving toward a single‐payer system will reduce BIR costs, certain reforms to payer‐provider contracts could generate at least as many administrative cost savings without radically reforming the entire health system. BIR costs can be meaningfully reduced without abandoning a multi‐payer system.
Show Me the Money! Dividend Policy in Countries with Weak Institutions
Authors: ELLAHIE ATIF , KAPLAN ZACHARY
Published: March 2021

We hypothesize that, in weak‐institution countries, firms adjust the ‘timing’ of dividend payments by committing to distribute a percentage of current earnings as dividends, revealing the extent of firm‐level agency conflicts to future investors and facilitating the raising of external capital. Consistent with this hypothesis, we find that, on average, firms in weak‐institution countries have a higher speed of adjustment (SOA) to their target payout ratio, pay dividends earlier in the life cycle, and are more likely to disclose a dividend policy committing to pay a minimum percentage of earnings. Within‐country tests show that, in weak‐institution countries, the firms with the highest SOA dividend policies have fewer agency problems and an increased ability to raise external capital. Finally, returns tests around earnings announcements show that high‐SOA dividend policies are associated with larger market reactions to earnings in weak‐institution countries. Collectively, our findings suggest that dividend policy helps to alleviate agency conflicts in weak‐institution countries between firms and (future) investors.
Petrology and Geochemistry of Some Ophiolitic Metaperidotites from the Eastern Desert of Egypt: Insights into Geodynamic Evolution and Metasomatic Processes
Authors: ABDEL‐KARIM Abdel‐Aal M. , AZER Mokhles K. , EL‐SHAFEI Shaimaa A.
Published: March 2021

Ophiolitic peridotites exposed in the Eastern Desert (ED) of Egypt record multiple stages of evolution, including different degrees of partial melting and melt extraction, serpentinization, carbonatization and metamorphism. The present study deals with metaperidotites at two selected localities in the central and southern ED, namely Wadi El‐Nabá and Wadi Ghadir, respectively. They represent residual mantle sections of a Neoproterozoic dismembered ophiolite that tectonically emplaced over a volcano‐sedimentary succession that represents island–arc assemblages. The studied metaperidotites are serpentinized, with the development of talc‐carbonate and quartz‐carbonate rocks, especially along shear and fault planes. Fresh relics of primary minerals (olivine, orthopyroxene and Cr‐spinel) are preserved in a few samples of partially‐serpentinized peridotite. Most of the Cr‐spinel crystals have fresh cores followed by outer zones of ferritchromite and Cr‐magnetite, which indicates that melt extraction from the mantle protolith took place under oxidizing conditions. The protoliths of the studied metaperidotites were dominated by harzburgites, which is supported by the abundance of mesh and bastite textures in addition to some evidence from mineral and whole‐rock chemical compositions. The high Cr#(0.62–0.69; Av. 0.66) and low TiO2(<0.3 wt%) contents of the fresh Cr‐spinels, the higher Fo (89–92; Av. 91) and NiO (0.24–0.54 wt%, Av. 0.40) contents of the primary olivine relics, together with the high Mg#(0.91–0.93; Av. 91) and low CaO, Al2O3and TiO2of the orthopyroxene relics, are all comparable with depleted to highly depleted forearc harzburgite from a suprasubduction zone setting. The investigated peridotites have suffered subsequent phases of metasomatism, from ocean‐floor hydrothermal alteration (serpentinization) to magmatic hydrothermal alteration. The enrichment of the studied samples in light rare earth elements (LREEs) relative to the heavy ones (HREEs) is attributed to most probably be due to the contamination of their mantle source with granitic source hydrothermal fluids after the obduction of the ophiolite assemblage onto the continental crust. The examined rocks represent mantle residue that experienced different degrees of partial melting (∼10% to 25% for W. El‐Nabá rocks and ∼5% to 23% for W. Ghadir rocks). Variable degrees of partial melting among the two investigated areas suggest mantle heterogeneity beneath the Arabian‐Nubian Shield (ANS).
A Rapid Marine Regression in the Southwestern Tarim Basin in the Latest Cretaceous: Comparison of Two Different Evaporitic Sequences in the Yarkand Basin, Xinjiang Province, China
Authors: CAO Yangtong , ZENG Changmin , ZHANG Liang , ZHU Lichun
Published: March 2021

Two different evaporitic sequences occurred in the latest Cretaceous–Early Paleocene in Yarkand Basin, southwestern Tarim Basin, Xinjiang Province, China: one is characterized by poor gypsum and some small, lenticular‐shaped halite layers in the Tuyiluoke Formation of the latest Cretaceous, the other is characterized by very thick gypsum and halite layers in the Aertashen Formation of the early Paleocene. In the early developmental stage of the Tuyiluoke Formation, the Yarkand ancient saline lake was a long, strip‐shaped depression, NW–SE oriented, along the West Kunlun piedmont, with its eastern boundary to the line along bores Ys1‐T1‐Ks101, the concentrated center located in the area of borehole S1. In the later developmental stage, the depositional scope was shifted inch by inch to the NW of this saline lake, forming a triangular depositional area, with apices at boreholes Wx1, Ak2 and S1, the concentrated center of the saline lake gradually migrating from borehole S1 region to the northwestern area of the lake, developing four small, evaporated‐concentrated sub‐depressions, depositing lenticular‐shaped halite. In the early Paleocene, the ancient saline lake was stretched from the West Kunlun piedmont in the west, to the Markit slope in the east, from the South Tianshan piedmont in the north, to the Hotan area in the south, accompanied by giant thicknesses of halite and large‐scale gypsum layers, mainly interbedded with limestone in the Aertashen Formation. The evaporites in the latest Cretaceous‐early Paleocene were controlled by the marine transgression‐regression geological background in the Yarkand Basin. Generally, integrated evaporitic depositional sequences, such as clasolite‐gypsum‐halite‐potash, usually occur in the presence of persistent seawater through evaporation, but this is not the case in the Tuyiluoke Formation. In contrast, very thick gypsum layers are common in the early Paleocene. Typically, adequate mineral sources for evaporites are found within seawater, such as in large basins undergoing long‐term marine transgression‐regression cycles, where adequate seawater remains, even though the basin was going through a marine regression stage. In the latest Cretaceous, thin gypsum layers indicate a lack of mineral sources. In contrast, the early Paleocene has far larger evaporites, both in width and thickness. This suggests a short‐term marine regression stage must have occurred during the spatiotemporal evolution of the evaporites in the latest Cretaceous–Early Paleocene in the basin, meaning that a rapid marine regressive episode has been identified at the end of the Cretaceous.
Biodiversity Soup II: A bulk‐sample metabarcoding pipeline emphasizing error reduction
Authors: Yang Chunyan , Bohmann Kristine , Wang Xiaoyang , Cai Wang , Wales Nathan , Ding Zhaoli , Gopalakrishnan Shyam , Yu Douglas W.
Published: March 2021

Despite widespread recognition of its great promise to aid decision‐making in environmental management, the applied use of metabarcoding requires improvements to reduce the multiple errors that arise during PCR amplification, sequencing and library generation. We present a co‐designed wet‐lab and bioinformatic workflow for metabarcoding bulk samples that removes both false‐positive (tag jumps, chimeras, erroneous sequences) and false‐negative (‘dropout’) errors. However, we find that it is not possible to recover relative‐abundance information from amplicon data, due to persistent species‐specific biases.

To present and validate our workflow, we created eight mock arthropod soups, all containing the same 248 arthropod morphospecies but differing in absolute and relative DNA concentrations, and we ran them under five different PCR conditions. Our pipeline includes qPCR‐optimized PCR annealing temperature and cycle number, twin‐tagging, multiple independent PCR replicates per sample, and negative and positive controls. In the bioinformatic portion, we introduce Begum, which is a new version of DAMe (Zepeda‐Mendoza et al., 2016. BMC Res. Notes 9:255) that ignores heterogeneity spacers, allows primer mismatches when demultiplexing samples and is more efficient. Like DAMe, Begum removes tag‐jumped reads and removes sequence errors by keeping only sequences that appear in more than one PCR above a minimum copy number per PCR. The filtering thresholds are user‐configurable.

We report that OTU dropout frequency and taxonomic amplification bias are both reduced by using a PCR annealing temperature and cycle number on the low ends of the ranges currently used for the Leray‐FolDegenRev primers. We also report that tag jumps and erroneous sequences can be nearly eliminated with Begum filtering, at the cost of only a small rise in dropouts. We replicate published findings that uneven size distribution of input biomasses leads to greater dropout frequency and that OTU size is a poor predictor of species input biomass. Finally, we find no evidence for ‘tag‐biased’ PCR amplification.

To aid learning, reproducibility, and the design and testing of alternative metabarcoding pipelines, we provide our Illumina and input‐species sequence datasets, scripts, a spreadsheet for designing primer tags and a tutorial.
Differential price‐responsiveness of smoking behaviors among non‐Hispanic African Americans and non‐Hispanic whites in the United States
Authors: Wang Yingning , Max Wendy , Yao Tingting , Keeler Courtney , Sung Hai‐Yen
Published: March 2021

Background and aims

Non‐Hispanic African Americans (African Americans) smoke fewer cigarettes per day (CPD) and are more likely to be non‐daily smokers than non‐Hispanic whites (whites). Little is known about how changes in cigarette prices might contribute to these differences. This study aimed to measure the price‐responsiveness of smoking participation, non‐daily smoking among current smokers and smoking intensity among daily or non‐daily smokers for African Americans and compare the price‐responsiveness estimates with those for whites.

Design

Analysis of data from the 2009–14 National Adult Tobacco Surveys and cigarette price data from the Tax Burden on Tobacco report.

Setting

United States.

Participants

A total of 19 232 African American and 197 939 white adults aged 18+.

Measurements

We used a three‐part econometric model of cigarette demand to estimate the price‐responsiveness of smoking participation, daily versus non‐daily smoking and smoking intensity. The model controlled for secular variation, state‐level anti‐smoking sentiment and smoke‐free air laws and socio‐demographics.

Findings

In 2009–14, 20.2% of African Americans and 17.7% of whites identified as current smokers; 70.2% of African American smokers and 81.4% of white smokers smoked daily. The price elasticity of smoking participation was significant for whites at −0.16 [95% confidence interval (CI) = –0.23, –0.09], indicating that a 10% increase in prices would reduce smoking participation by 1.6%, but not statistically significant for African Americans, and this racial/ethnic differential price responsiveness was not statistically significant. The price elasticity of smoking intensity was statistically significant for African American daily smokers at −0.29 (95% CI = −0.42, –0.16), but not statistically significant for white daily smokers, and this racial/ethnic differential price‐responsiveness was statistically significant. The price elasticity of daily versus non‐daily smoking among current smokers, and the price elasticity of smoking intensity among non‐daily smokers were not statistically significant for either racial/ethnic group.

Conclusion

In the United States, cigarette price increases may have stronger effects on decreasing daily smokers’ consumption among African Americans than among non‐Hispanic whites.
Development of a scale assessing retired older adults’ attitudes to volunteering
Authors: Dana Liyuwork Mitiku , Jongenelis Michelle I. , Jackson Ben , Newton Robert U. , Pettigrew Simone
Published: March 2021

Objective

Given positive attitudes to volunteering are likely to be associated with support for volunteering and individual participation, this study aimed to develop and test a 10‐item ‘attitudes to formal volunteering’ scale for retired older adults that could be used to inform intervention efforts.

Method

A sample of 801 Australian retirees (62% female; mean age: 71.9 years) completed a survey that included the attitude scale, demographic items and questions assessing engagement in volunteering.

Results

A principal component analysis identified two factors (general attitude to volunteering and attitude to participating in volunteering) that together accounted for 64% of the variance in attitude scores. A confirmatory factor analysis indicated the two‐factor model was an excellent fit to the data. Cronbach's alphas for both factors were >0.80, and both were positively associated with volunteering engagement.

Conclusion

The proposed scale is a potentially useful instrument for measuring attitudes to volunteering among retired older adults.
Loneliness in older age: What is it, why is it happening and what should we do about it in Australia?
Authors: Ogrin Rajna , Cyarto Elizabeth V. , Harrington Karra D. , Haslam Catherine , Lim Michelle H. , Golenko Xanthe , Bush Matiu , Vadasz Danny , Johnstone Georgina , Lowthian Judy A.
Published: March 2021

Loneliness is an important health issue facing older people due to its association with poor quality of life and poor health outcomes. This paper aimed to clarify key issues around loneliness among older adults and draw attention to innovative programs and the translation of emerging research into practice. Loneliness is a mismatch between a person's actual and desired social connections, experienced as negative emotions. Older adults are vulnerable to loneliness because of changes associated with ageing. As such, identifying as older is often seen as a burden, negatively impacting self‐esteem, sense of purpose and relevance, culminating in loneliness. Interventions combatting loneliness can target individuals, relationships, communities or societies. We advocate for an intersectoral approach to support healthy ageing and reduce loneliness. This will require further research to evaluate new approaches with loneliness as the primary outcome, and additional funding to translate evidence into an integrated multi‐level approach to addressing loneliness.
Neoliberalism and the Crisis in Higher Education: The Cost of Ideology
Authors: Mintz Beth
Published: March 2021

A number of factors have contributed to the crisis in higher education, including the long‐term transformation in funding. In this article, I argue that neoliberalism can explain many of the processes leading to our changing commitment to colleges and universities and the cost increases that this change has produced. A number of neoliberal assumptions firmly rooted in conventional wisdom have contributed to a “student‐as‐customer” phenomenon, which is, itself, a cost driver. I look at the development of the student as customer as a vehicle for exploring tuition increases. I also examine the tension between education as a public and a private good and the marketization of higher education as crucial drivers of these transformations. In doing so, I emphasize that the student as customer has been created by the changes in the way we think about, organize, and fund education, rather than any fundamental change in young people.
Nanoarchitectures for efficient IgE cross‐linking on effector cells to study amoxicillin allergy
Authors: Tesfaye Amene , Rodríguez‐Nogales Alba , Benedé Sara , Fernández Tahía D. , Paris Juan L. , Rodriguez Maria J. , Jiménez‐Sánchez Isabel M. , Bogas Gador , Mayorga Cristobalina , Torres María J. , Montañez María I.
Published: March 2021

Background

Amoxicillin (AX) is nowadays the β‐lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo tests and non‐optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic. Knowing adduct structural features for promoting effector cell activation would help to improve in vitro tests. We aimed to identify the optimal structural requirement in specific cellular degranulation to AX using well‐precised nanoarchitectures of different lengths.

Method

We constructed eight Bidendron Antigens (BiAns) based on polyethylene glycol (PEG) linkers of different lengths (600–12,000 Da), end‐coupled with polyamidoamine dendrons that were terminally multi‐functionalized with amoxicilloyl (AXO). In vitro IgE recognition was studied by competitive radioallergosorbent test (RAST) and antibody–nanoarchitecture complexes by transmission electron microscopy (TEM). Their allergenic activity was evaluated using bone marrow‐derived mast cells (MCs) passively sensitized with mouse monoclonal IgE against AX and humanized RBL‐2H3 cells sensitized with polyclonal antibodies from sera of AX‐allergic patients.

Results

All BiAns were recognized by AX‐sIgE. Dose‐dependent activation responses were observed in both cellular assays, only with longer structures, containing spacers in the range of PEG 6000–12,000 Da. Consistently, greater proportion of immunocomplexes and number of antibodies per complex for longer BiAns were visualized by TEM.

Conclusions

BiAns are valuable platforms to study the mechanism of effector cell activation. These nanomolecular tools have demonstrated the importance of the adduct size to promote effector cell activation in AX allergy, which will impact for improving in vitro diagnostics.
Hypertension affects the treatment of wet age‐related macular degeneration
Authors: Wang Ting , Xia Jun , Yuan Meng , Wu Xiaohang , Zhu Yi , Chen Chuan , Bergunder Sean J. , Liu Zhenzhen , Chen Wenben , Huang Kai , Lin Haotian
Published: March 2021

Purpose

Due to population ageing as well as the high prevalence of hypertension and age‐related macular degeneration (AMD) in elderly individuals, and the relationship between hypertension and AMD is unclear. Our research aimed to investigate the association between hypertension, wet AMD (wAMD) and the treatment strategy of wAMD patients affected by hypertension.

Methods

Data of wAMD patients at Zhongshan Ophthalmic Center, Sun Yat‐sen University, between 1 January 2002 and 30 June 2019, were extracted from the electronic healthcare information system. wAMD patients were divided into subgroups by hypertension status, age, sex, the need for vitrectomy surgery and the number of anti‐VEGF drug intravitreal injections that these were divided in 1–3 vs. >3 (available time from 1 January 2012 to 30 June 2019).

Results

A total of 3096 wAMD patients (41.7% female, 58.3% male) with an age range of 50–96 years (68.7 (SD 9.42) years) were included. wAMD was significantly associated with hypertension (p < 0.001). After adjustment for sex and age, Cox regression model showed a significant association between hypertension in wAMD patients and the number of injections (RR = 1.31, 95% CI: 1.13–1.50, p < 0.001). There was no significant association between hypertension and the need for vitrectomy (p = 0.82).

Conclusions

wet AMD was associated with hypertension status, and after the regular series of three injections, wAMD patients with hypertension were more likely to receive anti‐VEGF drug intravitreal injections than those without hypertension. These results may facilitate prospective research on the prevention of wAMD and contribute to the management of wAMD patients.
Antithyroid drug use during pregnancy and the risk of birth defects in offspring: systematic review and meta‐analysis of observational studies with methodological considerations
Authors: Morales Daniel R. , Fonkwen Lionel , Nordeng Hedvig M. E.
Published: March 2021

Aims

Maternal antithyroid drug (ATD) use during pregnancy has been associated with an increased risk of birth defects in offspring. Uncertainty remains on the size of this risk and how it compares to untreated hyperthyroidism due to methodological limitations of previous studies.

Methods

Systematic review of MEDLINE and EMBASE identifying observational studies examining ATD use during pregnancy and risk of birth defects by 28 August 2020. Data were extracted on study characteristics, effect estimates and comparator groups. Adjusted effect estimates were pooled using a random‐effects generic inverse variance method and absolute risk calculated.

Results

Seven cohort studies and 1 case–control study involving 6 212 322 pregnancies and 388 976 birth defects were identified reporting regression effect estimates. Compared to an unexposed population comparison, the association between ATD use during pregnancy and birth defects in offspring was: adjusted risk ratio (aRR) 1.16 95% confidence interval (CI) 1.08–1.25 for propylthiouracil (PTU); aRR 1.28 95%CI 1.06–1.54 for methimazole/carbimazole (MMI/CMZ); aRR 1.51, 95%CI 1.16–1.97 for both MMI/CMZ and PTU; and aRR 1.15 95%CI 1.02–1.29 for untreated hyperthyroidism. The excess risk of any and major birth defects per 1000, respectively, was: 10.2 and 1.3 for PTU; 17.8 and 2.3 for MMI/CMZ; 32.5 and 4.1 for both MMI/CMZ and PTU; and 9.6 and 1.2 for untreated hyperthyroidism.

Conclusions

When appropriately analysed the risk of birth defects associated with ATD use in pregnancy is attenuated. Although still elevated, the risk of birth defects is smallest with PTU compared to MMI/CMZ and may be similar to that of untreated hyperthyroidism.
Population pharmacokinetics and genetics of oral meltdose tacrolimus (Envarsus) in stable adult liver transplant recipients
Authors: Martial Lisa C. , Biewenga Maaike , Ruijter Bastian N. , Keizer Ron , Swen Jesse J. , van Hoek Bart , Moes Dirk Jan A. R.
Published: March 2021

Aims

Meltdose tacrolimus (Envarsus) is marketed as a formulation with a more consistent exposure. Due to the narrow therapeutic window, therapeutic drug monitoring is essential to maintain adequate exposure. The primary objective of this study was to develop a population pharmacokinetic (PK) model of Envarsus among liver transplant patients and select a limited sampling strategy (LSS) for AUC estimation. The secondary objective was to investigate potential covariates including CYP3A/IL genotype suitable for initial dose optimization when converting to Envarsus.

Methods

Adult liver transplant patients were converted from prolonged release tacrolimus (Advagraf) to Envarsus and blood samples were obtained using whole blood and dried blood spot sampling. Subsequently the population PK parameters were estimated using nonlinear‐mixed effect modelling. Demographic factors, and recipient and donor CYP3A4, CYP3A5, IL‐6, ‐10 and ‐18 genotype were tested as potential covariates to explain interindividual variability.

Results

Fifty‐five patients were included. A 2‐compartment model with delayed absorption was the most suitable to describe population PK parameters. The population PK parameters were as follows: clearance, 3.27 L/h; intercompartmental clearance, 9.6 L/h; volume of distribution of compartments 1 and 2, 95 and 500 L, respectively. No covariates were found to significantly decrease interindividual variability. The best 3‐point LSS was t = 0,4,8 with a median bias of 1.8% (−12.5–12.5).

Conclusions

The LSS can be used to adequately predict the AUC. No clinically relevant covariates known to influence the PK of Envarsus, including CYP3A status, were identified and therefore do not seem useful for initial dose optimization.
A transformation‐free linear regression for compositional outcomes and predictors
Authors: Fiksel Jacob , Zeger Scott , Datta Abhirup
Published: March 2021

Compositional data are common in many fields, both as outcomes and predictor variables. The inventory of models for the case when both the outcome and predictor variables are compositional is limited, and the existing models are often difficult to interpret in the compositional space, due to their use of complex log‐ratio transformations. We develop a transformation‐free linear regression model where the expected value of the compositional outcome is expressed as a single Markov transition from the compositional predictor. Our approach is based on estimating equations thereby not requiring complete specification of data likelihood and is robust to different data‐generating mechanisms. Our model is simple to interpret, allows for 0s and 1s in both the compositional outcome and covariates, and subsumes several interesting subcases of interest. We also develop permutation tests for linear independence and equality of effect sizes of two components of the predictor. Finally, we show that despite its simplicity, our model accurately captures the relationship between compositional data using two datasets from education and medical research.
On polygenic risk scores for complex traits prediction
Authors: Zhao Bingxin , Zou Fei
Published: March 2021

Polygenic risk scores (PRS) have gained substantial attention for complex traits prediction in genome‐wide association studies (GWAS). Motivated by the polygenic model of complex traits, we study the statistical properties of PRS under the high‐dimensional but sparsity free setting where the triplet with being the sample size, the number of assayed single‐nucleotide polymorphisms (SNPs), and the number of assayed causal SNPs, respectively. First, we derive asymptotic results on the out‐of‐sample (prediction) R‐squared for PRS. These results help understand the widespread observed gap between the in‐sample heritability (or partial R‐squared due to the genetic features) estimate and the out‐of‐sample R‐squared for most complex traits. Next, we investigate how features should be selected (e.g., by a p‐value threshold) for constructing optimal PRS. We reveal that the optimal threshold depends largely on the genetic architecture underlying the complex trait and the sample size of the training GWAS, or the ratio. For highly polygenic traits with a large ratio, it is difficult to separate causal and null SNPs and stringent feature selection in principle often leads to poor PRS prediction. We numerically illustrate the theoretical results with intensive simulation studies and real data analysis on 33 complex traits with a wide range of genetic architectures in the UK Biobank database.
External validation of International Prognostic Score for asymptomatic early stage chronic lymphocytic leukaemia and proposal of an alternative score
Authors: Smolej Lukáš , Turcsányi Peter , Kubová Zuzana , Zuchnická Jana , Mihályová Jana , Šimkovič Martin , Vodárek Pavel , Krčméryová Mária , Móciková Heidi , Brejcha Martin , Špaček Martin ,   Czech CLL Study Group
Published: March 2021

Most patients with chronic lymphocytic leukaemia (CLL) are nowadays diagnosed without any symptoms and do not require therapy. A prognostic score identifying patients within this large group who are at high risk of disease progression would be highly beneficial. The recently published International Prognostic Score for Early asymptomatic patients (IPS‐E) uses combination of absolute lymphocyte count (ALC) >15 × 109/l, palpable lymphadenopathy, and unmutated immunoglobulin heavy‐chain variable‐region (IGHV) gene to predict the time to first‐line therapy (TTFT). Patients at low, intermediate, and high risk had estimated 5‐year TTFT of 8%, 28%, and 61%. We performed an external validation of the IPS‐E score using an unselected, consecutive group of 130 Binet A patients. The 5‐year TTFT was 11%, 36%, and 78% (C‐statistic 0·74). Furthermore, we propose an alternative system (AIPS‐E) using cytogenetic aberrations instead of palpable lymphadenopathy. This system yielded 5‐year TTFT of 14%, 40%, and 72%. These results were externally validated in 388 Binet A patients from five Czech centres; the 5‐year TTFT was 16%, 37%, and 80% (C‐statistic 0·74). In conclusion, we have successfully validated the IPS‐E score for patients with early stage CLL. In addition, we propose a modified scoring system, the AIPS‐E, combining IGHV, fluorescence in situ hybridisation, and ALC.
Cardiovascular and temperature adverse actions of stimulants
Authors: Docherty James R. , Alsufyani Hadeel A.
Published: March 2021

The vast majority of illicit stimulants act at monoaminergic systems, causing both psychostimulant and adverse effects. Stimulants can interact as substrates or antagonists at the nerve terminal monoamine transporter that mediates the reuptake of monoamines across the nerve synaptic membrane and at the vesicular monoamine transporter (VMAT‐2) that mediates storage of monoamines in vesicles. Stimulants can act directly at presynaptic or postsynaptic receptors for monoamines or have indirect monoamine‐mimetic actions due to the release of monoamines. Cocaine and other stimulants can acutely increase the risk of sudden cardiac death. Stimulants, particularly MDMA, in hot conditions, such as that occurring at a “rave,” have caused fatalities from the consequences of hyperthermia, often compounding cardiac adverse actions. This review examines the pharmacology of the cardiovascular and temperature adverse actions of stimulants.
Beneficial intergenerational effects of exercise on brain and cognition: a multilevel meta‐analysis of mean and variance
Authors: Yang Yefeng , Lagisz Malgorzata , Foo Yong Zhi , Noble Daniel W. A. , Anwer Hamza , Nakagawa Shinichi
Published: March 2021

Physical exercise not only helps to improve physical health but can also enhance brain development and cognition. Recent reports on parental (both maternal and paternal) effects raise the possibility that parental exercise may provide benefits to offspring through intergenerational inheritance. However, the general magnitude and consistency of parental exercise effects on offspring is still controversial. Additionally, empirical research has long overlooked an important aspect of exercise: its effects on variability in neurodevelopmental and cognitive traits. Here, we compiled data from 52 studies involving 4786 rodents (412 effect sizes) to quantify the intergenerational transmission of exercise effects on brain and cognition. Using a multilevel meta‐analytic approach, we found that, overall, parental exercise showed a tendency for increasing their offspring's brain structure by 12.7% (albeit statistically non‐significant) probably via significantly facilitating neurogenesis (16.5%). Such changes in neural anatomy go in hand with a significant 20.8% improvement in neurobehaviour (improved learning and memory, and reduced anxiety). Moreover, we found parental exercise significantly reduces inter‐individual differences (i.e. reduced variance in the treatment group) in progeny's neurobehaviour by 10.2% (coefficient of variation ratio, lnCVR), suggesting the existence of an individual by intervention interaction. The positive effects of exercise are modulated by several covariates (i.e. moderators), such as the exercised parent's sex, offspring's sex, and age, mode of exercise, and exercise timing. In particular, parental forced exercise is more efficient than voluntary exercise at significantly improving offspring neurobehaviour (26.0%) and reducing its variability (14.2%). We observed larger effects when parental exercise started before pregnancy. However, exercising only during pregnancy also had positive effects. Mechanistically, exercise significantly upregulated brain‐derived neurotrophic factor (BDNF) by 28.9%, vascular endothelial growth factor (VEGF) by 35.8%, and significantly decreased hippocampal DNA methylation by 3.5%, suggesting that brain growth factor cascades and epigenetic modifications can moderate the transmission of parental exercise effects. Collectively, by coupling mean with variance effects, our analyses draw a more integrated picture of the benefits that parental exercise has on offspring: not only does it improve offspring brain development and cognitive performance, but it also reduces inter‐individual differences in cognition‐related traits. We advocate that meta‐analysis of variation together with the mean of a trait provides novel insights for old controversies as well as emerging new questions, opening up a new era for generating variance‐based hypotheses.
Debate: The role of inpatient units is to support community care
Authors: Stanton Josephine
Published: March 2021

In child and adolescent mental health care, the evidence base we have is for care in the community. The role of inpatient units is to support that care. Risk can be effectively managed in the context of acute psychotic illness. Some contribution can be made with suicidal adolescents, including sharing risk. Particular aspects of inpatient care can contribute to community care in many scenarios in terms of use of different sorts of assessment information, extended 24/7 contact enabling different opportunities for building rapport and shifting systems and stuck behaviour patterns. To support community teams effectively when such support is needed, inpatient units need to maintain empty beds. Self‐determination Theory provides an evidence base showing that when people experience relatedness, autonomy and competence, they experience increased well‐being, and intrinsic motivation can guide inpatient care. Interactions with patients and families, staff in the unit and community teams the unit is serving can be focussed to optimise experience of relatedness, autonomy and competence in all these groups. The potential is for every interaction to be a therapeutic interaction.
VPS33B interacts with NESG1 to suppress cell growth and cisplatin chemoresistance in ovarian cancer
Authors: Ning Yingxia , Zeng Zhaoyang , Deng Yuao , Feng Weifeng , Huang Lun , Liu Huiling , Lin Jiazhi , Zhang Chen , Fan Yue , Liu Longyang
Published: March 2021

The pathogenesis and cisplatin chemoresistance of ovarian cancer (OC) are still unclear. Vacuolar protein sorting‐associated 33B (VPS33B) has not been reported in OC to date. In this study, immunohistochemistry was used to detect VPS33B protein expression between OC and ovarian tissues. MTT, EdU, colony formation, cell cycle, in vivo tumorigenesis, western blot, ChIP, EMSA, co‐immunoprecipitation (CoIP), qRT‐PCR, and microconfocal microscopy were used to explore the function and molecular mechanisms of VPS33B in OC cells. The results of the present study demonstrated that VPS33B protein expression was obviously reduced in OC compared with that in ovarian tissues. Overexpressed VPS33B suppressed cell cycle transition, cell growth, and chemoresistance to cisplatin in vitro and in vivo. Analysis of the mechanism indicated that overexpressed VPS33B regulated the epidermal growth factor receptor (EGFR)/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop and reduced the expression of the cell cycle factor CDK4. Nasopharyngeal epithelium‐specific protein 1 (NESG1) as a tumor suppressor not only interacted with VPS33B, but was also induced by VPS33B by the attenuation of PI3K/AKT/c‐Jun‐mediated transcription inhibition. Overexpressed NESG1 further suppressed cell growth by mediating VPS33B‐modulated signals in VPS33B‐overexpressing OC cells. Finally, NESG1 induced VPS33B expression by reducing the inhibition of PI3K/AKT/c‐Jun‐mediated transcription. Our study is the first to demonstrate that VPS33B serves as a tumor suppressor, and VPS33B can interact with NESG1 to suppress cell growth and promote cisplatin sensitivity by regulating the EGFR/PI3K/AKT/c‐Myc/p53/miR‐133a‐3p feedback loop in OC cells.
Identification of cancer driver genes using Sleeping Beauty transposon mutagenesis
Authors: Takeda Haruna , Jenkins Nancy A. , Copeland Neal G.
Published: March 2021

Cancer genome sequencing studies have identified driver genes for a variety of different cancers and helped to understand the genetic landscape of human cancer. It is still challenging, however, to identify cancer driver genes with confidence simply from genetic data alone. In vivo forward genetic screens using Sleeping Beauty (SB) transposon mutagenesis provides another powerful genetic tool for identifying candidate cancer driver genes in wild‐type and sensitized mouse tumors. By comparing cancer driver genes identified in human and mouse tumors, cancer driver genes can be identified with additional confidence based upon comparative oncogenomics. This review describes how SB mutagenesis works in mice and focuses on studies that have identified cancer driver genes in the mouse gastrointestinal tract.
Examining the Effects of Changes in Classroom Quality on Within‐Child Changes in Achievement and Behavioral Outcomes
Authors: Watts Tyler W. , Nguyen Tutrang , Carr Robert C. , Vernon‐Feagans Lynne , Blair Clancy
Published: March 2021

This study examines whether changes in classroom quality predict within‐child changes in achievement and behavioral problems in elementary school (ages spanning approximately 6–11 years old). Drawing on data from a longitudinal study of children in predominantly low‐income, nonurban communities (n = 1,078), we relied on child fixed effects modeling, which controlled for stable factors that could bias the effects of classroom quality. In general, we found that changes in classroom quality had small and statistically nonsignificant effects on achievement and behavior. However, we found that moving into a high‐quality classroom, particularly those rated as high in Classroom Organization, had positive effects on achievement and behavior for children with significant exposure to poverty in early life.