Category: Statistics

Environ Int. 2021 May 30;155:106667. doi: 10.1016/j.envint.2021.106667. Online ahead of print.

ABSTRACT

INTRODUCTION: Asthma is a complex, heterogeneous disease and one of the most common chronic diseases among children. Exposure to ambient air pollution in early life and childhood may influence asthma aetiology, but it is uncertain which specific components of air pollution and exposure windows are of importance. The role of socio-economic status (SES) is also unclear. The aims of the present study are, therefore, to investigate how various exposure windows of different pollutants affect risk-induced asthma in early life and to explore the possible effect SES has on that relationship.

METHODS: The study population was constructed using register data on all singleton births in the greater Stockholm area between 2006 and 2013. Exposure to ambient black carbon (BC), fine particulate matter (PM_2.5), primary organic carbon (pOC) secondary organic aerosols (SOA), secondary inorganic aerosols, and oxidative potential at the residential address was modelled as mean values for the entire pregnancy period, the first year of life and the first three years of life. Swedish national registers were used to define the outcome: asthma diagnosis assessed at hospital during the first six years of life. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were modelled with Cox proportional hazards model with age as the underlying time-scale, adjusting for relevant potential confounding variables.

RESULTS: An increased risk for developing childhood asthma was observed in association with exposure to PM_2.5, pOC and SOA during the first three years of life. With an interquartile range increase in exposure, the HRs were 1.06 (95% CI: 1.01-1.10), 1.05 (95% CI: 1.02-1.09) and 1.02 (95% CI: 1.00-1.04), for PM_2.5, pOC and SOA, respectively, in the fully adjusted models. Exposure during foetal life or the first year of life was not associated with asthma risk, and the other pollutants were not statistically significantly associated with increased risk. Furthermore, the increase in risk associated with PM_2.5 and the components BC, pOC and SOA were stronger in areas with lower SES.

CONCLUSION: Our results suggest that exposure to air pollution during the first three years of life may increase the risk for asthma in early childhood. The findings further imply a possible increased vulnerability to air pollution-attributed asthma among low SES children.

PMID:34077855 | DOI:10.1016/j.envint.2021.106667

Oral Oncol. 2021 May 30;119:105328. doi: 10.1016/j.oraloncology.2021.105328. Online ahead of print.

ABSTRACT

OBJECTIVE: Alcohol use among survivors of head and neck cancer (HNC) negatively impacts patient outcomes and is an important risk factor for recurrent and second primary tumors. Despite recommendations from several cancer societies, alcohol consumption remains a common problem in this population.

METHODS: A cross-sectional study was performed with the Alcohol Use Disorders Identification Test (AUDIT) Self-Report questionnaire. Patients with HNC completed surveys at pre-treatment and follow-up appointments every 3-6 months for at least 2-years after treatment.

RESULTS: 796 surveys were available for analysis. Most participants were male (75.7%) and had either oropharyngeal (34.5%) or laryngeal (16.7%) cancer. The percentage of alcohol drinkers decreased from 56.1% at pre-treatment to 40.4% at 0-3 months post-treatment, but then increased and surpassed baseline levels by 24 + months post-treatment (64.4%, p = 0.0079). Concurrently, moderate drinkers (AUDIT = 1 – 3) decreased from 34.2% at pre-treatment to 25.2% at 0-3 months post-treatment, but then increased and surpassed baseline levels at 24 + months post-treatment (39.7%, p = 0.0129). Trends among heavy (AUDIT > 3), and heaviest (AUDIT > 6) drinkers were similar, but not statistically significant. At 24 + months post-therapy, we observed a statistically significant increase in female users (39.1% to 63.2%, p = 0.0213) and moderate drinkers < 55 years old (43.4% to 61.9%, p = 0.0184).

CONCLUSION: Alcohol consumption in survivors of HNC transiently decreases in the immediate months after treatment, but then increases and remains largely stable by 24 months. This pattern is particularly concerning and highlights the need for timely interventions.

PMID:34077813 | DOI:10.1016/j.oraloncology.2021.105328

J Clin Epidemiol. 2021 May 30:S0895-4356(21)00170-0. doi: 10.1016/j.jclinepi.2021.05.018. Online ahead of print.

ABSTRACT

Covid-19 research made it painfully clear that the scandal of poor medical research, as denounced by Altman in 1994, persists today. The overall quality of medical research remains poor, despite longstanding criticisms. The problems are well known, but the research community fails to properly address them. We suggest most problems stem from an underlying paradox: although methodology is undeniably the backbone of qualitative and responsible research, science consistently undervalues methodology. The focus remains more on the destination (research claims and metrics) than on the journey. Notwithstanding, research should serve society more than the reputation of those involved. While we notice that many initiatives are being established to improve components of the research cycle, these initiatives are too disjointed. The overall system is monolithic and slow to adapt. We assert that a top-down action is needed from journals, universities, funders and governments to break the cycle and put methodology first. These actions should involve the widespread adoption of registered reports, balanced research funding between innovative, incremental and methodological research projects, full recognition and demystification of peer review, mandatory statistical review of reports, adherence to reporting guidelines, and investment in methodological education and research. Currently, the scientific enterprise is doing a major disservice to patients and society.

PMID:34077797 | DOI:10.1016/j.jclinepi.2021.05.018

J Dent. 2021 May 30:103706. doi: 10.1016/j.jdent.2021.103706. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated the importance of defining the reference and the test object during 3D surface comparisons to assess the trueness of an intraoral scanner.

MATERIALS AND METHODS: A maxillary complete-arch cast with interdental spaces was digitized with a high-resolution scanner to obtain the ground truth dataset [GT]. Fifteen intraoral scanning datasets [IOS] were obtained with an intraoral scanner. The trueness of the [IOS] datasets were evaluated by two different comparison procedures using a 3D analysis software: In the first comparison [REF-GT], the [GT] dataset was set as reference object and the [IOS] dataset was defined as test object. In the second comparison [REF-IOS], the [IOS] dataset were set as reference object and the [GT] dataset was defined as test object. The mean trueness of both comparisons was calculated with absolute mean deviation, (90-10)/2 percentile, and root-mean-squared (RMS) error method. Statistical significance was analyzed using the t-test (α=.05).

RESULTS: The mean trueness values of [REF-GT] were 31.4(±6.1) µm for (90-10)/2 percentile, 77.0(±5.3) µm for absolute mean deviation, and 203.1(±4.8) µm for RMS error method. [REF-IOS] revealed 23.9(±4.8) µm, 28.3(±6.3) µm, and 39.6(±9.5) µm, respectively. The results differed significantly.

CONCLUSION: The datasets obtained from the intraoral scanner captured more adequately interproximal spaces in comparison to the [GT] dataset. Therefore, the [GT] dataset defined as reference object in the analysis software for 3D comparisons revealed misleading results.

CLINICAL SIGNIFICANCE: The selection of the reference object and of the areas to be compared have to be defined carefully regarding complete arch scanning accuracy analysis.

PMID:34077800 | DOI:10.1016/j.jdent.2021.103706

J Dent. 2021 May 30:103708. doi: 10.1016/j.jdent.2021.103708. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the effect of rapid high-intensity light-curing on the marginal integrity of four bulk-fill composites, including two materials specifically designed for high-intensity curing.

METHODS: Class V cavities were prepared on buccal surfaces of intact human molars with simulated pulpal pressure, filled in a single increment and light-cured using a conventional (10 s @ 1,340 mW/cm²) or high-intensity (3 s @ 3,440 mW/cm²) protocol. The restorations were subjected to thermo-mechanical loading (TML) comprising 1,200,000 mechanical loading cycles and 3,000 thermocycles. Quantitative margin analysis was performed before and after TML using a scanning electron microscope, and the marginal integrity was expressed as percentage of continuous margin (PCM).

RESULTS: All PCM values measured before TML were statistically similar regardless of the material and curing protocol (p>0.05). A statistically significant effect of the curing protocol (p=0.021) was identified only after TML for one material. PCM was significantly diminished by TML (p<0.001) for most combinations of material and curing protocol. The PCM values of the sculptable composites after TML were statistically similar regardless of the curing protocol (p>0.05). Compared to these values, significantly lower PCM after TML was identified for the flowable composites cured with the high-intensity protocol (p=0.001-0.045).

CONCLUSION: In most cases, high-intensity and conventional curing generally led to similar marginal integrity. Although all of the investigated composites initially performed similarly well, the flowable composites light-cured using the high-intensity protocol showed a significantly inferior marginal integrity compared to the sculptable composites after loading.

CLINICAL SIGNIFICANCE: Rapid high-intensity light-curing cannot be recommended for flowable bulk-fill composites since it may compromise the tooth-restoration interface.

PMID:34077801 | DOI:10.1016/j.jdent.2021.103708

Am J Hum Genet. 2021 May 25:S0002-9297(21)00189-0. doi: 10.1016/j.ajhg.2021.05.005. Online ahead of print.

ABSTRACT

Cupping of the optic nerve head, a highly heritable trait, is a hallmark of glaucomatous optic neuropathy. Two key parameters are vertical cup-to-disc ratio (VCDR) and vertical disc diameter (VDD). However, manual assessment often suffers from poor accuracy and is time intensive. Here, we show convolutional neural network models can accurately estimate VCDR and VDD for 282,100 images from both UK Biobank and an independent study (Canadian Longitudinal Study on Aging), enabling cross-ancestry epidemiological studies and new genetic discovery for these optic nerve head parameters. Using the AI approach, we perform a systematic comparison of the distribution of VCDR and VDD and compare these with intraocular pressure and glaucoma diagnoses across various genetically determined ancestries, which provides an explanation for the high rates of normal tension glaucoma in East Asia. We then used the large number of AI gradings to conduct a more powerful genome-wide association study (GWAS) of optic nerve head parameters. Using the AI-based gradings increased estimates of heritability by ∼50% for VCDR and VDD. Our GWAS identified more than 200 loci associated with both VCDR and VDD (double the number of loci from previous studies) and uncovered dozens of biological pathways; many of the loci we discovered also confer risk for glaucoma.

PMID:34077762 | DOI:10.1016/j.ajhg.2021.05.005

Can J Cardiol. 2021 May 30:S0828-282X(21)00285-3. doi: 10.1016/j.cjca.2021.05.009. Online ahead of print.

ABSTRACT

The COVID-19 crisis led to a flurry of clinical trials activity. The COVID-Evidence database shows 2,814 COVID-19 randomized trials registered as of February 16, 2021. Most were small (only 18% have a planned sample size >500) and the rare completed ones have not provided published results promptly (only 283 trial publications as of 2/2021). Small randomized trials and observational, non-randomized analyses have not had a successful track record and have generated misleading expectations. Different large trials on the same intervention have generally been far more efficient in producing timely and consistent evidence. The rapid generation of evidence and accelerated dissemination of results have led to new challenges for systematic reviews and meta-analyses (e.g. rapid, living, and scoping reviews). Pressure to regulatory agencies has also mounted with massive emergency authorizations, but some of them have had to be revoked. Pandemic circumstances have disrupted the way trials are conducted; therefore, new methods have been developed and adopted more widely to facilitate recruitment, consent, and overall trial conduct. Based on the COVID-19 experience and its challenges, planning of several large, efficient trials, and wider use of adaptive designs may change the future of clinical research. Pragmatism, integration in clinical care, efficient administration, promotion of collaborative structures, and enhanced integration of existing data and facilities may be several of the legacies of COVID-19 on future randomized trials.

PMID:34077789 | DOI:10.1016/j.cjca.2021.05.009

Acta Paediatr. 2021 Jun 2. doi: 10.1111/apa.15964. Online ahead of print.

ABSTRACT

AIM: Malnutrition is a major public health issue that has been associated with high susceptibility for impaired brain development and mental functioning. However, to date studies on this topic have not been collated and appraised. This systematic review and meta-analysis investigated the association between malnutrition and cognitive development.

METHODS: We searched the MEDLINE, Scopus, CINAHL, Embase PsycINFO and Cochrane Library databases in English up to 8 December 2020. All studies reporting an association between nutritional status and cognitive development were included. P values of less than 0.05 were considered statistically significant and the results are reported as standardised mean differences (SMD), 95% confidence intervals (95%) and I² statistics.

RESULTS: We included 12 studies comprising 7,607 participants aged 1 to 12 years. Children with malnutrition had worse scores than controls for the Wechsler Intelligence Scale (SMD -0.40; 95% CI -0.60 to -0.20; p<0.0001; I² 77.1%), the Raven’s Coloured Progressive Matrices (SMD -3.75; 95% CI -5.68 to -1.83; p<0.0001; I² 99.2%), visual processing (SMD -0.85; 95% CI -1.23 to -0.46; p 0.009; I² 11.0%) and short memory (SMD 0.85; 95% CI -1.21 to -0.49; p<0.0001; I² 0%) tests.

CONCLUSION: Normal cognitive development requires access to good and safe nutrition.

PMID:34077582 | DOI:10.1111/apa.15964

Plant Biotechnol J. 2021 Jun 2. doi: 10.1111/pbi.13645. Online ahead of print.

ABSTRACT

Starch is the most abundant storage carbohydrate in maize kernels and provides calories for humans and other animals as well as raw materials for various industrial applications. Decoding of the genetic basis of natural variation in kernel starch content is needed to manipulate starch quantity and quality via molecular breeding to meet future needs. Here, we identified 50 unique single quantitative trait loci (QTLs) for starch content with 18 novel QTLs via single linkage mapping, joint linkage mapping, and a genome-wide association study in a multi-parent population containing six recombinant inbred line populations. Only five QTLs explained over 10% of phenotypic variation in single populations. In addition to a few large-effect and many small-effect additive QTLs, limited pairs of epistatic QTLs also contributed to the genetic basis of the variation in kernel starch content. A regional association study identified five non-starch-pathway genes that were the causal candidate genes underlying the identified QTLs for starch content. The pathway-driven analysis identified ZmTPS9, which encodes a trehalose-6-phosphate synthase in the trehalose pathway, as the causal gene for the QTL qSTA4-2, which was detected by all three statistical analyses. Knockout of ZmTPS9 increased kernel starch content and, in turn, kernel weight in maize, suggesting potential applications for ZmTPS9 in maize starch and yield improvement. These findings extend our knowledge about the genetic basis of starch content in maize kernels and provide valuable information for maize genetic improvement of starch quantity and quality.

PMID:34077617 | DOI:10.1111/pbi.13645

Ann Bot. 2021 Jun 2:mcab065. doi: 10.1093/aob/mcab065. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Secondary metabolites are integral to multiple key plant processes: growth regulation, pollinator attraction, interactions with conspecifics, competitors and symbionts, yet their role in plant adaptation remains an underexplored area of research. Carnivorous plants use secondary metabolites to acquire nutrients from prey, but the extent of the role of secondary metabolites in plant carnivory is not known. We aimed to determine the extent of the role of secondary metabolites in facilitating carnivory of the Cape sundew, Drosera capensis.

METHODS: We conducted metabolomic analysis of 72 plants in a time-series experiment before and after simulated prey capture. We used UHPLC-MS/MS and retention time index to identify compounds in the leaf trap tissue which changed up to 72 hrs following simulated prey capture. We identified associated metabolic pathways, and cross-compared these compounds to metabolites previously known to be involved in carnivorous plants across taxa.

KEY RESULTS: For the first time in a carnivorous plant, we have profiled the whole-leaf metabolome response to prey capture. Reliance on secondary plant metabolites was higher than previously thought-2383 out of 3257 compounds in fed leaves had statistically significant concentration changes in comparison to unfed controls. Of these, ~34 compounds are also associated with carnivory in other species; 11 are unique to Nepenthales. At least 20 compounds had 10-fold changes in concentration, 12 of which had 30-fold changes and are typically associated with defence or attraction in non-carnivorous plants.

CONCLUSIONS: Secondary plant metabolites are utilised in plant carnivory to an extent greater than previously thought-we found a whole metabolome response to prey capture. Plant carnivory, at the metabolic level, likely evolved from at least two distinct functions-attraction and defence. Findings of this study support the hypothesis that secondary metabolites play an important role in plant diversification and adaptation to new environments.

PMID:34077503 | DOI:10.1093/aob/mcab065