Publications by authors named "Nathan Miller"

137 Publications

Use of Botulinum Toxin A to Treat Chemotherapy-Induced Raynaud's Phenomenon.

Cureus 2021 Jan 5;13(1):e12511. Epub 2021 Jan 5.

Division of Plastic & Reconstructive Surgery, Lehigh Valley Health Network, Allentown, USA.

Raynaud's phenomenon (RP) is a vasospastic disorder of the digital blood vessels leading to pain, paresthesias, and pallor in response to cold or stress. RP can develop secondary to a number of pathologies or factors, including the use of chemotherapy agents. Typical first-line therapies for secondary RP may be contraindicated in patients with certain comorbidities. Here, we discuss a case in which botulinum toxin A (BTX-A) was used to treat chemotherapy-induced RP in a patient with non-small cell lung cancer (NSCLC). We provide a review of the existing literature on the clinical course and treatment modalities, including the use of BTX-A, for patients with secondary RP. A 56-year-old female with NSCLC received treatment with bevacizumab and pemetrexed. Her initial symptoms included progressive discoloration and pain in her fingertips, which hastily progressed to ischemia and subsequent dry gangrene. She was diagnosed with chemotherapy-induced RP, but traditional management options were complicated by acute congestive heart failure. BTX-A injections were administered at key locations on the wrist and hand, significantly improving her symptoms and slowing the progression of the gangrenous changes. RP can develop as sequelae of chemotherapy regimens. Clinical management may be complicated by underlying pathology and/or patient symptoms. BTX-A injections are an excellent non-operative therapeutic option for patients with secondary RP in cases where mainstay therapies may be contraindicated, thus decreasing pain, improving patient quality of life, and slowing the progression of gangrenous changes.
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http://dx.doi.org/10.7759/cureus.12511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863048PMC
January 2021

Community health workers in humanitarian settings: Scoping review.

J Glob Health 2020 Dec;10(2):020602

Save the Children, Washington, D.C., USA.

Background: There is a need for greater understanding of experiences implementing community-based primary health care in humanitarian settings and of the adjustments needed to ensure continuation of essential services and utilization of services by the population, and to contribute to effective emergency response. We reviewed the evidence base on community health workers (CHWs) in humanitarian settings, with the goal of improving delivery of essential services to the most vulnerable populations.

Methods: We conducted a scoping review of published and grey literature related to health and nutrition services provided by CHWs in humanitarian settings. Extracted data from retained documents were analyzed inductively for key themes.

Results: Of 3709 documents screened, 219 were included in the review. Key findings from the literature include: 1) CHWs were often able to continue providing services during acute and protracted crises, including prolonged periods of conflict and insecurity and during population displacement. 2) CHWs carried out critical emergency response activities during acute crises. 3) Flexible funding facilitated transitions between development and humanitarian programming. 4) Communities that did not have a locally-resident CHW experienced reduced access to services when travel was limited. 5) Community selection of CHWs and engagement of respected local leaders were crucial for community trust and acceptance and high utilization of services. 6) Selection of local supervisors and use of mobile phones facilitated continued supervision. 7) Actions taken to maintain supplies included creating parallel supply chains, providing buffer stocks to CHWs, and storing commodities in decentralized locations. 8) When travel was restricted, reporting and data collection were continued using mobile phones and use of local data collectors. 9) CHWs and supervisors faced security threats and psychological trauma as a result of their work.

Conclusions: To achieve impact, policy makers and program implementers will have to address the bottlenecks to CHW service delivery common in stable low-income settings as well as the additional challenges unique to humanitarian settings. Future interventions should take into account the lessons learned from years of experience with implementation of community-based primary health care in humanitarian settings. There is also a need for rigorous assessments of community-based primary health care interventions in humanitarian settings.
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http://dx.doi.org/10.7189/jogh.10.020602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719274PMC
December 2020

The availability of global guidance for the promotion of women's, newborns', children's and adolescents' health and nutrition in conflicts.

BMJ Glob Health 2020 11;5(Suppl 1)

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland

Background: Significant global gains in sexual, reproductive, maternal, newborn, child and adolescent health and nutrition (SRMNCAH&N) will be difficult unless conflict settings are adequately addressed. We aimed to determine the amount, scope and quality of publically available guidance documents, to characterise the process by which agencies develop their guidance and to identify gaps in guidance on SRMNCAH&N promotion in conflicts.

Methods: We identified guidance documents published between 2008 and 2018 through English-language Internet sites of humanitarian response organisations, reviewed them for their scope and assessed their quality with the AGREE II (Appraisal of Guidelines for REsearch and Evaluation II) tool. Additionally, we interviewed 22 key informants on guidance development, dissemination processes, perceived guidance gaps and applicability.

Findings: We identified 105 conflict-relevant guidance documents from 75 organisations. Of these, nine were specific to conflicts, others were applicable also to other humanitarian settings. Fifteen documents were technical normative guidelines, others were operational guides (67), descriptive documents (21) or advice on legal, human rights or ethics questions (2). Nutrition was the most addressed health topic, followed by communicable diseases and violence. The documents rated high quality in their 'scope and purpose' and 'clarity of presentation' and low for 'rigour of development' and 'editorial independence'. Key informants reported end user need as the primary driver for guideline development and WHO technical guidelines as their main evidence base. Insufficient local contextualisation, lack of inter-agency coordination and lack of systematic implementation were considered problems in guideline development. Several guidance gaps were noted, including abortion care, newborn care, early child development, mental health, adolescent health beyond sexual and reproductive health and non-communicable diseases.

Interpretation: Organisations are motivated and actively producing guidance for SRMNCAH&N promotion in humanitarian settings, but few documents address conflicts specifically and there are important guidance gaps. Improved inter-organisation collaboration for guidance on SRMNCAH&N promotion in conflicts and other humanitarian settings is needed.
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http://dx.doi.org/10.1136/bmjgh-2019-002060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684670PMC
November 2020

Double Spiral Dupuytren's Disease: Case of Ulnar and Radial Spiral Cords in Shared Digit.

Plast Reconstr Surg Glob Open 2020 Oct 28;8(10):e3212. Epub 2020 Oct 28.

Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Md.

Dupuytren's disease is a benign fibroproliferative disorder resulting in progressive contraction of palmar and digital fascia. Diseased fascia of the hand condenses into tensile cords, manifesting in various anatomical combinations. The spiral cord variant is especially troublesome, as the cord travels under the digital neurovascular bundle and places it at risk during surgical resection. In severe cases, limited fasciectomy is required to release contracture and restore finger extension. Here, we present the case of a 79-year-old right-handed man with a history of severe Dupuytren's disease of both hands, who was found to have and spiral cords in his right ring finger. Diseased tissue was removed en bloc, restoring extension and function. To our knowledge, this is the first case of a digit with two spiral cords affecting both neurovascular bundles. It is important to be aware of the anatomical variations possible in Dupuytren's disease to avoid iatrogenic injury.
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http://dx.doi.org/10.1097/GOX.0000000000003212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647618PMC
October 2020

Implementing integrated community case management during conflict in Yemen.

J Glob Health 2020 Dec;10(2):020601

Save the Children Yemen, Sana'a, Yemen.

Background: The conflict in Yemen has devastated the health system, with only 51% of health facilities classified as fully functional and 19.7 million people lacking access to health care. To address the urgent need for primary health care services in rural communities, Save the Children launched an iCCM program in Lahj and Taiz Governorates. A qualitative study was conducted to document the challenges to iCCM service delivery and to aid in developing strategies for overcoming service delivery bottlenecks in conflict-affected rural areas.

Methods: Qualitative data were collected in Aden City, Lahj Governorate, and Taiz Governorate. Twenty-three IDIs and six FGDs were conducted with iCCM stakeholders at all levels.

Results: Key findings included: 1) Policy, coordination, and funding were challenged by the fact that iCCM was not integrated into the national health system and was implemented as a short-term emergency program. 2) Villages that received services from a CHW who was based in a different community experienced reduced access to services, especially during times of heightened conflict and insecurity, when CHWs could not travel. 3) Supervision, supply chain, and monitoring were all challenges that were exacerbated by difficulties in travel due to the conflict. Potential solutions to these included the use of mobile technology for supervision and data collection and pre-positioning of buffer stocks in locations closer to CHWs. 4) Travel was seen as the primary threat to the safety of CHWs and supervisors. Measures taken to reduce the risk included limiting travel during periods of heightened insecurity, safety training for CHWs, and use of mobile technology for communication.

Conclusions: CHWs were able to provide iCCM services in a challenging and insecure context. The challenges in delivery of services were related to both a weak health system and the conflict. Several adaptations to service delivery to overcome the bottlenecks have been identified and should be considered for future community health programs. The closure of the program in Taiz after only 14 months of implementation is a stark illustration of the failure of the current model of short-term humanitarian funding to address long-term needs in protracted emergencies.
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http://dx.doi.org/10.7189/jogh.10.020601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568935PMC
December 2020

The impact of direct-to-consumer wearables in pediatric electrophysiology telehealth clinics: A real-world case series.

Cardiovasc Digit Health J 2020 Nov-Dec;1(3):169-171. Epub 2020 Oct 7.

Division of Pediatric Cardiology, Washington University School of Medicine, St Louis, Missouri.

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http://dx.doi.org/10.1016/j.cvdhj.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538375PMC
October 2020

Illuminating dark fishing fleets in North Korea.

Sci Adv 2020 Jul 22;6(30):eabb1197. Epub 2020 Jul 22.

Global Fishing Watch, Washington, DC 20036, USA.

Illegal, unreported, and unregulated fishing threatens resource sustainability and equity. A major challenge with such activity is that most fishing vessels do not broadcast their positions and are "dark" in public monitoring systems. Combining four satellite technologies, we identify widespread illegal fishing by dark fleets in the waters between the Koreas, Japan, and Russia. We find >900 vessels of Chinese origin in 2017 and >700 in 2018 fished illegally in North Korean waters, catching an estimated amount of approximating that of Japan and South Korea combined (>164,000 metric tons worth >$440 million). We further find ~3000 small-scale North Korean vessels fished, mostly illegally, in Russian waters. These results can inform independent oversight of transboundary fisheries and foreshadow a new era in satellite monitoring of fisheries.
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http://dx.doi.org/10.1126/sciadv.abb1197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455503PMC
July 2020

Elevated preoperative C-reactive protein is associated with renal functional decline and non-cancer mortality in surgically treated renal cell carcinoma: analysis from the INternational Marker Consortium for Renal Cancer (INMARC).

BJU Int 2021 Mar 19;127(3):311-317. Epub 2020 Nov 19.

Department of Urology, UC San Diego School of Medicine, La Jolla, CA, USA.

Objective: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC).

Patients And Methods: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes.

Results: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m (HR 1.41, P = 0.023) and <30 mL/min/1.73 m (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001).

Conclusions: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.
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http://dx.doi.org/10.1111/bju.15200DOI Listing
March 2021

Characterizing introgression-by-environment interactions using maize near isogenic lines.

Theor Appl Genet 2020 Oct 15;133(10):2761-2773. Epub 2020 Jun 15.

Department of Agronomy and Plant Genetics, University of Minnesota, 1991 Upper Buford Circle, Saint Paul, MN, 55108, USA.

Key Message: Significant introgression-by-environment interactions are observed for traits throughout development from small introgressed segments of the genome. Relatively small genomic introgressions containing quantitative trait loci can have significant impacts on the phenotype of an individual plant. However, the magnitude of phenotypic effects for the same introgression can vary quite substantially in different environments due to introgression-by-environment interactions. To study potential patterns of introgression-by-environment interactions, fifteen near-isogenic lines (NILs) with > 90% B73 genetic background and multiple Mo17 introgressions were grown in 16 different environments. These environments included five geographical locations with multiple planting dates and multiple planting densities. The phenotypic impact of the introgressions was evaluated for up to 26 traits that span different growth stages in each environment to assess introgression-by-environment interactions. Results from this study showed that small portions of the genome can drive significant genotype-by-environment interaction across a wide range of vegetative and reproductive traits, and the magnitude of the introgression-by-environment interaction varies across traits. Some introgressed segments were more prone to introgression-by-environment interaction than others when evaluating the interaction on a whole plant basis throughout developmental time, indicating variation in phenotypic plasticity throughout the genome. Understanding the profile of introgression-by-environment interaction in NILs is useful in consideration of how small introgressions of QTL or transgene containing regions might be expected to impact traits in diverse environments.
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http://dx.doi.org/10.1007/s00122-020-03630-zDOI Listing
October 2020

Comparison of renal functional outcomes of active surveillance and partial nephrectomy in the management of oncocytoma.

World J Urol 2020 Jun 17. Epub 2020 Jun 17.

Department of Urology, UC San Diego School of Medicine, 3855 Health Sciences Drive, 0987, La Jolla, CA, 92093-0987, USA.

Purpose: To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma.

Methods: Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73m). Cox regression Multivariable analysis (MVA) was carried out for predictors of de novo CKD. Linear regression was carried out for factors associated with increasing deltaGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year CKD-free survival.

Results: 295 patients were analyzed (224 PN/71 AS, median follow-up 37.4 months). No differences were noted for clinical tumor size (AS 2.6 vs. PN 2.9 cm, p = 0.108), and baseline eGFR (AS 79.6 vs. PN 77, p = 0.9670). Median change in tumor diameter for AS was 0.42 cm. Compared to PN, AS had deltaGFR (-15.3 vs. -6.4 mL/min/1.73m, p < 0.001) and de novo CKD (28.2% vs. 12.1%, p = 0.002). AS patients who developed CKD had higher RENAL score (p = 0.005) and lower baseline eGFR (73 vs. 91.2 mL/min/1.73m, p < 0.001) than AS patients who did not. MVA demonstrated increasing age (OR = 1.03, p = 0.025), tumor size (HR = 1.26, p = 0.032) and AS (HR = 4.91, p < 0.001) to be predictive for de novo CKD. Linear regression demonstrated AS was associated with larger decrease in deltaGFR (B = -0.219, p < 0.001). KMA revealed 5-year CKD survival was higher in PN (87%) vs. AS (62%, p < 0.001).

Conclusion: AS was associated with greater functional decline than PN in oncocytoma. PN may be considered to optimalize renal functional preservation in select circumstances. Further investigation into mechanisms of functional decline in oncocytoma is requisite.
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http://dx.doi.org/10.1007/s00345-020-03299-5DOI Listing
June 2020

Clinical Validation of a Multi-Biomarker Assay for the Evaluation of Chronic Pain Patients in a Cross-Sectional, Observational Study.

Pain Ther 2020 Dec 3;9(2):511-529. Epub 2020 Jun 3.

Center for Pain Relief, 400 Court St Ste 100, Charleston, WV, 25301, USA.

Introduction: Chronic pain assessment and post-treatment evaluation continues to be challenging due to a lack of validated, objective tools to measure patient outcomes. Validation of mechanistic pain biomarkers would allow clinicians to objectively identify abnormal biochemistry contributing to painful symptoms.

Methods: We describe the clinical validation of a multi-biomarker assay with algorithmic analysis known as the Foundation Pain Index (FPI) in diverse cohorts of chronic pain patients in a prospective, cross-sectional, observational validation study. Levels of 11 urinary pain biomarkers were measured and tabulated using a proprietary algorithm to generate FPI scores for chronic pain subjects (N = 153) and age- and sex-matched pain-free controls (N = 334).

Results: FPI scores were significantly correlated with the 36-Item Short Form Health Survey (SF-36) scores among chronic pain subjects (P value < 0.015) and specific components of SF-36, including emotional well-being, limitations due to emotional problems, and general health (P value < 0.05). Area under ROC analysis (AUROC) revealed FPI to accurately distinguish biomarker profiles between pain-free and chronic pain cohorts (AUROC: 0.7490, P value < 0.0001) as well as the SF-36 scores between chronic pain subjects with low vs. high FPI scores (AUROC: 0.7715, P value < 0.01).

Conclusions: Our findings establish the validity and discriminatory power of a novel multi-biomarker test that evaluates the role of biochemistry in chronic pain and correlates with clinical assessments of patients. This test provides novel, reproducible, objective data which may pave the way for non-opioid therapeutic strategies to treat chronic pain.
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http://dx.doi.org/10.1007/s40122-020-00175-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648807PMC
December 2020

Assessing community health worker service delivery in humanitarian settings.

J Glob Health 2020 Jun;10(1):010307

Research, Evaluation, and Learning Unit, International Rescue Committee, Washington, D.C., USA.

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http://dx.doi.org/10.7189/jogh.10.010307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100867PMC
June 2020

Determining the Agreement Between an Automated Respiratory Rate Counter and a Reference Standard for Detecting Symptoms of Pneumonia in Children: Protocol for a Cross-Sectional Study in Ethiopia.

JMIR Res Protoc 2020 Apr 2;9(4):e16531. Epub 2020 Apr 2.

Malaria Consortium, London, United Kingdom.

Background: Acute respiratory infections (ARIs), primarily pneumonia, are the leading infectious cause of under-5 mortality worldwide. Manually counting respiratory rate (RR) for 60 seconds using an ARI timer is commonly practiced by community health workers to detect fast breathing, an important sign of pneumonia. However, correctly counting breaths manually and classifying the RR is challenging, often leading to inappropriate treatment. A potential solution is to introduce RR counters, which count and classify RR automatically.

Objective: This study aims to determine how the RR count of an Automated Respiratory Infection Diagnostic Aid (ARIDA) agrees with the count of an expert panel of pediatricians counting RR by reviewing a video of the child's chest for 60 seconds (reference standard), for children aged younger than 5 years with cough and/or difficult breathing.

Methods: A cross-sectional study aiming to enroll 290 children aged 0 to 59 months presenting to pediatric in- and outpatient departments at a teaching hospital in Addis Ababa, Ethiopia, was conducted. Enrollment occurred between April and May 2017. Once enrolled, children participated in at least one of three types of RR evaluations: (1) agreement-measure the RR count of an ARIDA in comparison with the reference standard, (2) consistency-measure the agreement between two ARIDA devices strapped to one child, and (3) RR fluctuation-measure RR count variability over time after ARIDA attachment as measured by a manual count. The agreement and consistency of expert clinicians (ECs) counting RR for the same child with the Mark 2 ARI timer for 60 seconds was also measured in comparison with the reference standard.

Results: Primary outcomes were (1) mean difference between the ARIDA and reference standard RR count (agreement) and (2) mean difference between RR counts obtained by two ARIDA devices started simultaneously (consistency).

Conclusions: Study strengths included the design allowing for comparison between both ARIDA and the EC with the reference standard RR count. A limitation is that exactly the same set of breaths were not compared between ARIDA and the reference standard since ARIDA can take longer than 60 seconds to count RR. Also, manual RR counting, even when aided by a video of the child's chest movements, is subject to human error and can result in low interrater reliability. Further work is needed to reach global consensus on the most appropriate reference standard and an acceptable level of agreement to provide ministries of health with evidence to make an informed decision on whether to scale up new automated RR counters.

Trial Registration: ClinicalTrials.gov NCT03067558; https://clinicaltrials.gov/ct2/show/NCT03067558.

International Registered Report Identifier (irrid): RR1-10.2196/16531.
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http://dx.doi.org/10.2196/16531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163412PMC
April 2020

Maize genomes to fields (G2F): 2014-2017 field seasons: genotype, phenotype, climatic, soil, and inbred ear image datasets.

BMC Res Notes 2020 Feb 12;13(1):71. Epub 2020 Feb 12.

University of Wisconsin, Madison, WI, 53706, USA.

Objectives: Advanced tools and resources are needed to efficiently and sustainably produce food for an increasing world population in the context of variable environmental conditions. The maize genomes to fields (G2F) initiative is a multi-institutional initiative effort that seeks to approach this challenge by developing a flexible and distributed infrastructure addressing emerging problems. G2F has generated large-scale phenotypic, genotypic, and environmental datasets using publicly available inbred lines and hybrids evaluated through a network of collaborators that are part of the G2F's genotype-by-environment (G × E) project. This report covers the public release of datasets for 2014-2017.

Data Description: Datasets include inbred genotypic information; phenotypic, climatic, and soil measurements and metadata information for each testing location across years. For a subset of inbreds in 2014 and 2015, yield component phenotypes were quantified by image analysis. Data released are accompanied by README descriptions. For genotypic and phenotypic data, both raw data and a version without outliers are reported. For climatic data, a version calibrated to the nearest airport weather station and a version without outliers are reported. The 2014 and 2015 datasets are updated versions from the previously released files [1] while 2016 and 2017 datasets are newly available to the public.
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http://dx.doi.org/10.1186/s13104-020-4922-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017475PMC
February 2020

Natal origin of Pacific bluefin tuna from the California Current Large Marine Ecosystem.

Biol Lett 2020 02 5;16(2):20190878. Epub 2020 Feb 5.

Pacific Bluefin Tuna Biology Group, Bluefin Tuna Resources Division, National Research Institute of Far Seas Fisheries, 5-7-1, Orido, Shimizu, Shizuoka 424-8633, Japan.

Natal origin of subadult (age-1) Pacific bluefin tuna (PBT, ) from the California Current Large Marine Ecosystem (CCLME) was determined using natural tracers in ear stones (otoliths). Age-0 PBT collected from the two known spawning areas in the western Pacific Ocean (East China Sea, Sea of Japan) were used to establish baseline signatures from otolith cores over 4 years (2014-2017) based on a suite of trace elements (Li, Mg, Mn, Sr, Zn and Ba). Distinct chemical signatures existed in the otolith cores of age-0 PBT collected from the two spawning areas, with overall classification accuracy ranging 73-93% by year. Subadult PBT collected in the CCLME over the following 4 years (2015-2018) were then age-class matched to baselines using mixed-stock analysis. Natal origin of trans-Pacific migrants in the CCLME ranged 43-78% from the East China Sea and 22-57% from the Sea of Japan, highlighting the importance of both spawning areas for PBT in the CCLME. This study provides the first estimates on the natal origin of subadult PBT in this ecosystem using otolith chemistry and expands upon the application of these natural tracers for population connectivity studies for this species.
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http://dx.doi.org/10.1098/rsbl.2019.0878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058956PMC
February 2020

The complex response of free and bound amino acids to water stress during the seed setting stage in Arabidopsis.

Plant J 2020 05 5;102(4):838-855. Epub 2020 Feb 5.

Division of Biological Sciences, Interdisciplinary Plant Group, Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO, 65211, USA.

Free amino acids (FAAs) and protein-bound amino acids (PBAAs) in seeds play an important role in seed desiccation, longevity, and germination. However, the effect that water stress has on these two functional pools, especially when imposed during the crucial seed setting stage is unclear. To better understand these effects, we exposed Arabidopsis plants at the seed setting stage to a range of water limitation and water deprivation conditions and then evaluated physiological, metabolic, and proteomic parameters, with special focus on FAAs and PBAAs. We found that in response to severe water limitation, seed yield decreased, while seed weight, FAA, and PBAA content per seed increased. Nevertheless, the composition of FAAs and PBAAs remained unaltered. In response to severe water deprivation, however, both seed yield and weight were reduced. In addition, major alterations were observed in both FAA and proteome compositions, which indicated that both osmotic adjustment and proteomic reprogramming occurred in these naturally desiccation-tolerant organs. However, despite the major proteomic alteration, the PBAA composition did not change, suggesting that the proteomic reprogramming was followed by a proteomic rebalancing. Proteomic rebalancing has not been observed previously in response to stress, but its occurrence under stress strongly suggests its natural function. Together, our data show that the dry seed PBAA composition plays a key role in seed fitness and therefore is rigorously maintained even under severe water stress, while the FAA composition is more plastic and adaptable to changing environments, and that both functional pools are distinctly regulated.
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http://dx.doi.org/10.1111/tpj.14668DOI Listing
May 2020

Approaches to support continued iCCM implementation during a flooding emergency in rural Bangladesh.

J Glob Health 2019 Dec;9(2):021001

Save the Children International, Dhaka, Bangladesh.

Background: More evidence is needed on how integrated community case management (iCCM) service delivery is affected and on how to maintain service availability during crises. This study documented the implementation of iCCM through two cadres of community health workers (community health care providers [CHCPs] and village doctors [VDs]) in communities that were affected by a 2015 flooding emergency in Bangladesh.

Methods: We conducted a retrospective case study to assess iCCM services provided by CHCPs and VDs during a flooding emergency that occurred from June to August 2015. We purposively selected nine unions within four sub-districts in Bhola District. In this mixed methods study, we analyzed trends in quantitative service delivery indicators over the time period from January 2015 to February 2016. Qualitative data were obtained through 28 in-depth interviews and 13 focus group discussions with policy makers, implementers, supervisors, CHCPs, VDs, community leaders, and caregivers of under-five children.

Results: All stakeholders reported disruptions in iCCM service delivery and in access to CHCPs and VDs for community members. The quantitative data showed a 30% reduction in average number of children who received treatment from both CHCPs and VDs during flooding months compared to pre-flood months (from 2273/month to 1593/month). There was also an increase in the number of children referred by CHCPs and VDs, reduced supervision, and increased stock-outs of commodities during the flooding months. CHCPs and VDs, in collaboration with community members, came up with several locally adapted initiatives to maintain iCCM services, including changing clinic hours according to the tide, organizing temporary clinics at alternative sites that were located on higher ground, use of community boats to visit clients in their homes, and use of mobile phones for communication with supervisors and community members.

Conclusion: Our study results demonstrate that iCCM services can continue during a natural disaster, albeit with significant disruptions. Ad hoc adaptations to services by local implementers and community members were key in maintaining availability of services during the emergency. In future emergencies, service delivery could be significantly strengthened by enacting key preparedness activities prior to a natural disaster such as severe flooding.
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http://dx.doi.org/10.7189/jogh.09.021001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925969PMC
December 2019

Risk Factors for Upstaging, Recurrence, and Mortality in Clinical T1-2 Renal Cell Carcinoma Patients Upstaged to pT3a Disease: An International Analysis Utilizing the 8th Edition of the Tumor-Node-Metastasis Staging Criteria.

Urology 2020 Apr 11;138:60-68. Epub 2019 Dec 11.

Department of Urology, University of California San Diego School of Medicine, La Jolla, California. Electronic address:

Objective: To investigate risk factors for and outcomes in pathological T3a-upstaging in Renal Cell Carcinoma (RCC), as Tumor-Node-Metastasis staging for T3a RCC was recently revised.

Methods: Multicenter retrospective analysis of patients with clinical T1-T2 RCC, stratified by occurrence of pathologic T3a-upstaging. Primary outcome was recurrence-free survival (RFS). Multivariable analyses (MVA) were conducted for upstaging and recurrence. Kaplan-Meier analysis (KMA) was utilized for RFS and overall survival (OS).

Results: We analyzed 2573 patients (1223 RN/1350 PN). Upstaging occurred in 360 (14.0%). On MVA, higher clinical stage was associated with increasing risk of upstaging [cT1a (referent), odds ratio for cT1b, cT2a, and cT2b was 2.6, 6.5, and 14.1, P < .001]. Higher clinical stage at presentation correlated with increasing risk of recurrence in pT3a-upstaged RCC (cT1a upstaged-pT3a [referent], hazard ratio [HR] for cT1b, cT2a, and cT2b upstaged pT3a was 1.16 [P = .729], 3.02 [P = .013], and 4.5 [P = .003]). Perirenal fat (HR 1.6, P = .038) and renal vein (HR 2.2, P = .006) invasion were associated with increased risk of recurrence; type of surgery was not (P = .157). KMA for RFS and OS in pT3a-upstaged patients demonstrated differences based on initial clinical stage (5-year PFS for cT1a/b, and cT2 upstaged was 84.5%/72.8%, and 44.7%, P < .001; 5-year OS for cT1 and cT2 upstaged was 83.8% and 63.2%, P < .001).

Conclusion: Risk of pT3a-upstaging and recurrence in pT3a-upstaged RCC correlates with clinical stage at presentation. Renal vein and perinephric fat invasion were associated with increased risk of recurrence. PN did not increase risk of recurrence and potential of pT3a-upstaging should not deter consideration of PN.
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http://dx.doi.org/10.1016/j.urology.2019.11.036DOI Listing
April 2020

Predicting Flowering Time, Yield, and Kernel Dimensions by Analyzing Aerial Images.

Front Plant Sci 2019 11;10:1251. Epub 2019 Oct 11.

Department of Botany, University of Wisconsin-Madison, Madison, WI, United States.

Image analysis methods for measuring crop phenotypes may replace traditional measurements if they more efficiently and reliably capture similar or superior information. This study used a recreational-grade unmanned aerial vehicle carrying a spectrally-modified consumer-grade camera to collect images in which each pixel value is a vegetation index based on the normalized difference between the blue and near infrared wavelength bands (BNDVI). The subjects of the study were hybrids with good yield potential grown in 4-row plots. Flights were conducted at least once per week during three successive growing seasons in south-central Wisconsin. Average BNDVI for each plot (genotype) rose steadily through June, peaked in July, and then declined as plants matured. BNDVI histograms changed shape over the season as the canopy concealed soil, became more uniformly green, then senesced. Principal Components Analysis (PCA) captured the change in histogram shape. PC1 represented canopy closure. PC2 represented the mean of the BNDVI distribution. PC3 represented the spread of the distribution. Correlation analysis showed that flowering time correlated with PC2 and PC3 best (r ≈ 0.5) a few days before the event (day in which 50% of the plants exhibited tassels). Three ears were picked from each plot to quantify kernel dimensions by image analysis before each plot was mechanically harvested to determine grain weight per plot. Correlations between this measurement of yield and PC2 were low in June but exceeded 0.4 within 10 days after flowering. Kernel length correlated similarly with PC2. The correlation between PC2 and kernel thickness displayed a similar but inverted time course. These results indicate that greater mid-season BNDVI values correlate positively with yield comprised of tall, thin kernels. Partial least squares regression performed on the BNDVI time courses predicted flowering time (r = 0.54-0.79) and yield (r = 0.4-0.69). This three-year experiment demonstrated that readily available hardware and software can create a phenotyping platform capable of predicting maize flowering time, yield, and kernel dimensions to a useful degree.
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http://dx.doi.org/10.3389/fpls.2019.01251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797588PMC
October 2019

Conservation of the genome-wide recombination rate in white-footed mice.

Heredity (Edinb) 2019 10 31;123(4):442-457. Epub 2019 Jul 31.

Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Despite being linked to the fundamental processes of chromosome segregation and offspring diversification, meiotic recombination rates vary within and between species. Recent years have seen progress in quantifying recombination rate evolution across multiple temporal and genomic scales. Nevertheless, the level of variation in recombination rate within wild populations-a key determinant of evolution in this trait-remains poorly documented on the genomic scale. To address this notable gap, we used immunofluorescent cytology to quantify genome-wide recombination rates in males from a wild population of the white-footed mouse, Peromyscus leucopus. For comparison, we measured recombination rates in a second population of male P. leucopus raised in the laboratory and in male deer mice from the subspecies Peromyscus maniculatus bairdii. Although we found differences between individuals in the genome-wide recombination rate, levels of variation were low-within populations, between populations, and between species. Quantification of synaptonemal complex length and crossover positions along chromosome 1 using a novel automated approach also revealed conservation in broad-scale crossover patterning, including strong crossover interference. We propose stabilizing selection targeting recombination or correlated processes as the explanation for these patterns.
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http://dx.doi.org/10.1038/s41437-019-0252-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781155PMC
October 2019

Outcomes of a Multicenter, Prospective, Crossover, Randomized Controlled Trial Evaluating Subperception Spinal Cord Stimulation at ≤1.2 kHz in Previously Implanted Subjects.

Neuromodulation 2020 Jan 2;23(1):102-108. Epub 2019 Jul 2.

Boston Scientific Corporation, Division of Neuromodulation, Valencia, CA, USA.

Objective: The WHISPER randomized controlled trial (RCT) evaluates safety and clinical effectiveness of subperception spinal cord stimulation (SCS) at ≤1.2 kHz in subjects previously implanted with an SCS system for treatment of chronic, neuropathic pain.

Methods: WHISPER is a prospective, multicenter RCT with a crossover design sponsored by Boston Scientific, Marlborough, MA (ClinicalTrials.gov: NCT02314000). Eligible subjects were randomized (N = 140) to receive subperception or supraperception for three months and then crossed over to receive the alternative. Upon completion of crossover period, subjects who preferred subperception were followed up to one year. Overall pain, quality-of-life, and other outcomes were collected in the study. The primary endpoint was the overall pain responder rate (≥50% improvement from baseline) with no increase in medications. Secondary endpoints consisted of pain scores, physical disability, quality of life, and treatment preference.

Results: The study met its primary endpoint and demonstrated noninferiority between supraperception and subperception in a prespecified cohort of 70 randomized subjects (Interim Analysis). Thirty-nine percent of subjects with subperception settings and 29% with supraperception settings had a greater than or equal to 50% reduction in their overall pain scores with no increase in average daily medication at three-months post-activation as compared with baseline. Further assessment of all participating study subjects (N = 140) revealed similar results. Subjects were previously implanted 3.8 ± 2 years and had a disability score (Oswestry Disability Index) of 70.2 ± 11.4 at study start. Of the randomized subjects that completed the End of Period 2 Visit, 93 (66%) preferred subperception SCS and their mean overall pain reduced from 7.3 ± 1.1 (N = 89) at baseline to 4.0 ± 2.1 (N = 80) at 12-months post-activation. Post hoc analysis also demonstrated that multiple options provide superior outcomes, as supported by a 74% increase in the responder rate when subjects could choose their most effective option (47%) compared with supraperception alone (27%).

Discussion: Subperception SCS at ≤1.2 kHz is safe and effective in subjects with extreme physical disability and previously implanted for chronic pain. Further, by providing study participants with different waveform options, increased pain relief was achieved.
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http://dx.doi.org/10.1111/ner.13015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004055PMC
January 2020

Classifying cold-stress responses of inbred maize seedlings using RGB imaging.

Plant Direct 2019 Jan 2;3(1):e00104. Epub 2019 Jan 2.

Department of Plant Pathology University of Minnesota St. Paul Minnesota.

Increasing the tolerance of maize seedlings to low-temperature episodes could mitigate the effects of increasing climate variability on yield. To aid progress toward this goal, we established a growth chamber-based system for subjecting seedlings of 40 maize inbred genotypes to a defined, temporary cold stress while collecting digital profile images over a 9-daytime course. Image analysis performed with PlantCV software quantified shoot height, shoot area, 14 other morphological traits, and necrosis identified by color analysis. Hierarchical clustering of changes in growth rates of morphological traits and quantification of leaf necrosis over two time intervals resulted in three clusters of genotypes, which are characterized by unique responses to cold stress. For any given genotype, the set of traits with similar growth rates is unique. However, the patterns among traits are different between genotypes. Cold sensitivity was not correlated with the latitude where the inbred varieties were released suggesting potential further improvement for this trait. This work will serve as the basis for future experiments investigating the genetic basis of recovery to cold stress in maize seedlings.
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http://dx.doi.org/10.1002/pld3.104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508840PMC
January 2019

A machine vision platform for measuring imbibition of maize kernels: quantification of genetic effects and correlations with germination.

Plant Methods 2018 21;14:115. Epub 2018 Dec 21.

1Department of Botany, University of Wisconsin, 430 Lincoln Drive, Madison, WI 53706 USA.

Background: Imbibition (uptake of water by a dry seed) initiates the germination process. An automated method for quantifying imbibition would enable research on the genetic elements that influence the underlying hydraulic and biochemical processes. In the case of crop research, a high throughput imbibition assay could be used to investigate seed quality topics or to improve yield by selecting varieties with superior germination characteristics.

Results: An electronic force transducer measured imbibition of single maize kernels with very high resolution but low throughput. An image analysis method was devised to achieve high throughput and sufficient resolution. A transparent fixture held 90 maize kernels in contact with water on the imaging window of a flatbed document scanner that produced an image of the kernels automatically every 10 min for 22 h. Custom image analysis software measured the area of each indexed kernel in each image to produce imbibition time courses. The ultimate change in area (ΔA) ranged from 19.3 to 23.4% in a population of 72 hybrids derived from 9 inbred parents. Kernel area as a function of time was fit well by where is the final kernel area. The swelling coefficient, , ranged from 0.098 to 0.159 h across the genotypes. The full diallel structure of the population enabled maternal genotype effects to be assessed. In a separate experiment, measurements of kernels of the same 25 inbreds produced in three different years demonstrated that production and storage variables affected imbibition much less than genotype. In a third experiment, measurements of 30 diverse inbred lines showed that varied inversely with germination time (r = - 0.7) and directly with germination percentage (r = 0.7).

Conclusions: Nonspecialized imaging hardware and custom analysis software running on public cyber infrastructure form a low-cost platform for measuring seed imbibition with high resolution and throughput. We measured imbibition of thousands of kernels to determine that genotype influenced imbibition of maize kernels much more than seed production and storage environments. In some hybrids, depended on which inbred parent was maternal. Quantitative relationships between and germination traits were discovered.
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http://dx.doi.org/10.1186/s13007-018-0383-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302439PMC
December 2018

An Automated Image Analysis Pipeline Enables Genetic Studies of Shoot and Root Morphology in Carrot ( L.).

Front Plant Sci 2018 27;9:1703. Epub 2018 Nov 27.

Department of Botany, University of Wisconsin-Madison, Madison, WI, United States.

Carrot is a globally important crop, yet efficient and accurate methods for quantifying its most important agronomic traits are lacking. To address this problem, we developed an automated image analysis platform that extracts components of size and shape for carrot shoots and roots, which are necessary to advance carrot breeding and genetics. This method reliably measured variation in shoot size and shape, petiole number, petiole length, and petiole width as evidenced by high correlations with hundreds of manual measurements. Similarly, root length and biomass were accurately measured from the images. This platform also quantified shoot and root shapes in terms of principal components, which do not have traditional, manually measurable equivalents. We applied the pipeline in a study of a six-parent diallel population and an F mapping population consisting of 316 individuals. We found high levels of repeatability within a growing environment, with low to moderate repeatability across environments. We also observed co-localization of quantitative trait loci for shoot and root characteristics on chromosomes 1, 2, and 7, suggesting these traits are controlled by genetic linkage and/or pleiotropy. By increasing the number of individuals and phenotypes that can be reliably quantified, the development of a rapid, automated image analysis pipeline to measure carrot shoot and root morphology will expand the scope and scale of breeding and genetic studies.
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http://dx.doi.org/10.3389/fpls.2018.01703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6277879PMC
November 2018

Extrapleural Superficial Solitary Fibrous Tumor on the Posterior Shoulder: A Case Report and Review of the Literature.

Eplasty 2018 11;18:e31. Epub 2018 Oct 11.

Lehigh Valley Physicians Group-Surgical Oncology, Allentown, Pa.

: Mesenchymal in origin, solitary fibrous tumors are primarily seen within the pleura of the lung or in serosal-lined body cavities. Constituting 1% to 2% of all soft-tissue tumors, solitary fibrous tumors are rare entities, especially when found in extrapleural and in superficial locations. A review of literature for superficial solitary fibrous tumors revealed 71 reports in case reports and small case series. : In this report, we describe a 74-year-old man with an extrapleural superficial solitary fibrous tumor, as well as present a review of the current published literature to date. : We present the clinical course, surgical procedure, histopathological features, and treatment options, as well as present a compilation of the published data on superficial solitary fibrous tumors. : Based on the current literature, solitary fibrous tumors are more common in middle-aged women and in the head and neck region. Diagnosis of solitary fibrous tumors requires tissue sampling and staining for immunohistochemical markers. Management of these tumors is based on wide local excision with histologically negative margins. If negative margins cannot be surgically achieved, adjuvant therapies including radiation have been described. With extrapleural manifestations of solitary fibrous tumors seldom reported in the literature, it is our hope that reporting these unusual instances will raise awareness of such disease manifestations and allow for earlier diagnosis and treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232949PMC
October 2018

Elements of time and place: manganese and barium in shark vertebrae reflect age and upwelling histories.

Proc Biol Sci 2018 11 7;285(1890). Epub 2018 Nov 7.

Department of Marine Biology, Texas A&M University at Galveston, 1001 Texas Clipper Road, Galveston, TX 77553, USA.

As upper-level predators, sharks are important for maintaining marine food web structure, but populations are threatened by fishery exploitation. Sustainable management of shark populations requires improved understanding of migration patterns and population demographics, which has traditionally been sought through physical and/or electronic tagging studies. The application of natural tags such as elemental variations in mineralized band pairs of elasmobranch vertebrae cartilage could also reveal endogenous and exogenous processes experienced by sharks throughout their life histories. Here, elemental profiles were characterized in vertebrae encompassing complete life histories (birth-to-death) of shortfin mako (), common thresher () and blue shark () of known tag and recapture locations in the eastern North Pacific Ocean. All sharks were injected with oxytetracycline at initial capture, released and subsequently recaptured, with individual liberty times ranging from 215 days to 6 years. Vertebral band pairs forming over the liberty intervals were verified by counting the number of band pairs deposited since the oxytetracycline band. Regular oscillations in vertebrae manganese (Mn) content corresponded well with the number of validated band pairs, suggesting that Mn variation could be used to age sharks. Increases in vertebrae barium concentration were correlated with times when individuals occupied areas with high coastal upwelling indices, the timing and spatial intensity of which varied from year to year. Interspecific relationships were probably influenced by behavioural differences in horizontal and vertical habitat use, feeding habits and thermoregulatory physiology. These results indicate that vertebral sclerochronology has the potential to advance our knowledge of elasmobranch life history including age and growth estimation and environmental reconstruction.
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http://dx.doi.org/10.1098/rspb.2018.1760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235039PMC
November 2018

Modulation of early maize seedling performance via priming under sub-optimal temperatures.

PLoS One 2018 5;13(11):e0206861. Epub 2018 Nov 5.

University of Florida, Horticultural Science Department, Gainesville, FL, United States of America.

Seeds planted in early spring frequently experience low temperature stress in the soil during germination and early plant growth. Seed pretreatments such as priming have been shown to ameliorate the negative effects of cold soil in some crops. However, the potential beneficial effects of priming have not been widely investigated for Zea mays (maize). To investigate seed priming effects, 24 diverse maize inbred lines were primed using a synthetic solid matrix, Micro-Cel E, and then exposed to 10°C soil conditions. Six DSLR cameras captured time lapsed images of emerging seedlings. Manual scoring was used to determine treatment effects on three seedling emergence metrics. Chilling substantially reduced total emergence for two of 24 genotypes evaluated. For these genotypes, priming provided protection allowing nearly full emergence. Priming significantly reduced mean emergence time and increased the emergence uniformity of chilling sensitive genotypes. The results suggest that the cold sensitive genotypes may benefit from priming pretreatment. Kernel density, weight, oil, protein, and starch traits, as determined by single-kernel near infrared spectroscopy, were not correlated with seedling emergence traits supporting a conclusion that early seedling performance cannot be determined from these maize kernel characteristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0206861PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218074PMC
April 2019