Defining the Middle Corona.

The middle corona, the region roughly spanning heliocentric distances from 1.5 to 6 solar radii, encompasses almost all of the influential physical transitions and processes that govern the behavior of coronal outflow into the heliosphere. The solar wind, eruptions, and flows pass through the region, and they are shaped by it. Importantly, the region also modulates inflow from above that can drive dynamic changes at lower heights in the inner corona. Consequently, the middle corona is essential for comprehensively connecting the corona to the heliosphere and for developing corresponding global models. Nonetheless, because it is challenging to observe, the region has been poorly studied by both major solar remote-sensing and in-situ missions and instruments, extending back to the Solar and Heliospheric Observatory (SOHO) era. Thanks to recent advances in instrumentation, observational processing techniques, and a realization of the importance of the region, interest in the middle corona has increased. Although the region cannot be intrinsically separated from other regions of the solar atmosphere, there has emerged a need to define the region in terms of its location and extension in the solar atmosphere, its composition, the physical transitions that it covers, and the underlying physics believed to shape the region. This article aims to define the middle corona, its physical characteristics, and give an overview of the processes that occur there.

Comparison of RT-qPCR and Digital PCR Methods for Wastewater-Based Testing of SARS-CoV-2

Wastewater-based epidemiology is an important tool for monitoring SARS-CoV-2 and other molecular targets in populations, using wastewater as a pooled sample. We compared the sensitivity, susceptibility to inhibition, and quantification of reverse transcription quantitative PCR (RT-qPCR), microfluidic well digital RT-PCR (RT-dPCR), and droplet digital RT-PCR (RT-ddPCR) measurements of SARS-CoV-2 (N1 gene target) and Pepper Mild Mottle Virus (PMMoV) RNA in 40 wastewater RNA extracts. All three methods were highly sensitive, but appeared less accurate at very low concentrations. Lower inhibition was observed for RT-ddPCR than RT-qPCR with both SARS-CoV-2 and PMMoV targets, but inhibition appeared to be mitigated by dilution of template RNA. The concentrations of N1 and PMMoV from all three methods were significantly correlated (Pearsons r=0.97-0.98 for N1 and r=0.89-0.93 for PMMoV), although RT-qPCR reported higher concentrations than digital methods. Taken together, this study provides support for the application of all three methods in wastewater-based epidemiology, with additional guidelines for the use of RT-qPCR. Impact StatementPCR-based assays are the current standard for sensitive, specific, rapid pathogen quantification in environmental samples, including wastewater. The increased availability of multiple digital PCR technologies necessitates side-by-side comparison between platforms, including traditional qPCR, to guide the application of these methods. Specifically, this work can inform interpretation of wastewater SARS-CoV-2 PCR data, as reported to public health agencies for pandemic response.

Methods to improve efficacy of orally administered bioactive peptides using bovine colostrum as an exemplar.

BACKGROUND: Oral administration of bioactive peptides has potential clinical advantages, but its applicability is limited due to gastric and pancreatic enzyme proteolysis. OBJECTIVE: To examine whether the co-packaging of bovine colostrum (BC), a rich source of IgG, immune and growth factors, with the food additives trehalose (carbohydrate), stearine (fat), casein (protein present in BC) or soy flour (plant based with high protease inhibitory activity) enhances the stability of BC against digestion. DESIGN: Samples alone and in combination (BC+ 10% wt/wt trehalose, stearine, casein or soy) were exposed to HCl/pepsin, followed by trypsin and chymotrypsin ("CT"). Assessment of proliferation used gastric AGS cells (Alamar blue), IgG function measured bovine IgG anti-E.coli binding and ELISAs quantified growth factor constituents. In vivo bioassay assessed ability of BC alone or with soy to reduce injury caused by dextran sodium sulphate (DSS, 4% in drinking water, 7 days, test products started 2 days prior to DSS). RESULTS: Proliferative activity of BC reduced 61% following HCl/pepsin and CT exposure. This was truncated 50% if soy was co-present, and also protected against loss of total IgG, IgG E.coli binding, TGFß, lactoferrin and EGF (all P<0.01 vs BC alone). Co-packaging with trehalose was ineffective in preventing digestion whereas casein or stearine provided some intermediate protective effects. Rats given BC alone showed beneficial effects on weight gain, disease activity index, tissue histology and colonic MPO. Soy alone was ineffective. BC+ soy combination showed the greatest benefit with a dose of 7 mg/kg (6.4 BC + 0.6 soy flour) having the same degree of benefit as using 20 mg/kg BC alone. CONCLUSION: Soy, and to a lesser extent casein, enhanced the biostability of BC against digestive enzymes. Co-packaging of BC with other food products such as soy flour could result in a decreased dose being required, improving cost-effectiveness and patient compliance.

Social trauma as a contributory factor in Filipino's vaccine hesitancy.

Despite of the Government's effort to persuade the public to participate in its vaccination program against COVID-19, vaccine hesitancy remains to be a big challenge in the Philippines. While various efforts were undertaken to promote the safety and efficacy of vaccines against COVID-19, it is imperative that the Philippine government considers social traumas as a factor in vaccine hesitancy. This study proposes Judith Herman's stages of trauma recovery as a possible framework that could be utilize by the government in its drive to increase public trust.

The IWill MCW Campaign: Individual Actions to Advance Gender Equity.

Advancing equity for women remains an urgent and complex problem at academic health centers. Attempts to mitigate gender gaps have ranged widely and have been both slow to occur and limited in effect. Recognizing the limitations of previously attempted solutions and fueled by the #MeToo and #TimesUp movements, the Medical College of Wisconsin (MCW) stepped outside known approaches (e.g., women's leadership plans and programming) to design and implement a strategic campaign that promotes gender equity through fostering change in systems and social norms. This campaign, IWill MCW (launched in 2019), emphasizes the power of individual responsibility for positive change. The IWill MCW campaign employs a 2-pronged approach. The first is the creation of personal call-to-action public pledges focused on 5 aspects of gender equity, along with the provision of supportive resources to reinforce positive change. The second is the use of those pledges to raise awareness of gender inequity in academic medicine by fostering meaningful dialogue meant to alter mental models of equity, relationships, and power dynamics. In the initial 6-week phase of the IWill MCW campaign, leaders reached out to all MCW faculty (2,002), staff (4,522), and learners (1,483) at multiple campuses. This outreach resulted in nearly 1,400 pledges, including 30% (n = 420) from men. The effort also engaged over 90% (n = 101) of members of MCW senior leadership teams. The feedback from the initial campaign has been positive. Lessons learned include realizing the importance of public pledges, engaging male allies, and following up. The authors suggest that the IWill MCW campaign provides a model for academic health centers to advance gender equity and shape an environment in which people of all genders can thrive.

Distressing healthcare workers during the COVID-19 pandemic: the challenges of holiday season in the Philippines.

The holiday season, Christmas to New Year, is the most festive period of each year in the Philippines. However, the beginning of the festive holiday season in the Philippines seems to be a predicament to healthcare workers and professionals especially during this coronavirus disease 2019 (COVID-19) pandemic. The holiday season is considered a health risk in the Philippines because of the change of lifestyle leading to the increased number of health consultancies and hospitalization. Thus, the expected surge of people in the hospitals and clinics pose an added stress to healthcare workers and professionals. Pre-Holiday policies and programs are therefore essentials especially during the course of battling COVID-19.

Bovine Colostrum: Its Constituents and Uses.

Colostrum is the milk produced during the first few days after birth and contains high levels of immunoglobulins, antimicrobial peptides, and growth factors. Colostrum is important for supporting the growth, development, and immunologic defence of neonates. Colostrum is naturally packaged in a combination that helps prevent its destruction and maintain bioactivity until it reaches more distal gut regions and enables synergistic responses between protective and reparative agents present within it. Bovine colostrum been used for hundreds of years as a traditional or complementary therapy for a wide variety of ailments and in veterinary practice. Partly due to concerns about the side effects of standard Western medicines, there is interest in the use of natural-based products of which colostrum is a prime example. Numerous preclinical and clinical studies have demonstrated therapeutic benefits of bovine colostrum for a wide range of indications, including maintenance of wellbeing, treatment of medical conditions and for animal husbandry. Articles within this Special Issue of Nutrients cover the effects and use bovine colostrum and in this introductory article, we describe the main constituents, quality control and an overview of the use of bovine colostrum in health and disease.

Building public trust: a response to COVID-19 vaccine hesitancy predicament.

With the rollout of vaccines against COVID-19, an optimistic and a negative attitude among people have arisen. Surprisingly, surveys among people reveal that there is a significant rate of distrust against the vaccines. In a recent short report published in this journal, vaccine hesitancy was found out among medical students. Hence, wide array of research has been springing, recommending various approaches in assisting authorities deal with vaccine hesitancy such as proper and effective strategic communication as a solution. This study suggests however that a more 'localized' public education and role-modelling from public officials and health authorities can help a lot in building public trust. The study aims to contribute to the further development of public health mechanisms in the rolling-out and distribution of vaccines against COVID-19.

Culture as a contributory factor in combatting the Covid-19 pandemic.

In a recent correspondence, the racial disparity was discussed regarding knowledge, attitudes and practices related to COVID-19. This paper highlights culture as a contributory factor in combatting the COVID-19 pandemic that is to be considered by each government around the world.

The Use of Bovine Colostrum in Medical Practice and Human Health: Current Evidence and Areas Requiring Further Examination.

Colostrum is produced by the mammary gland for the first few days following birth and is a rich natural source of macro- and micro-nutrients, immunoglobulins, and peptides with anti-microbial, immune modulatory and/or growth-factor activity [...].

Racial/Ethnic Differences In COVID-19 Screening, Hospitalization, And Mortality In Southeast Wisconsin.

This study aimed to understand racial/ethnic differences in coronavirus disease 2019 (COVID-19) screening, symptom presentation, hospitalization, and mortality, using data from 31,549 adults tested for COVID-19 between March 1 and July 10, 2020, in Milwaukee and Southeast Wisconsin. Racial/ethnic differences existed in adults who screened positive for COVID-19 (4.5 percent of non-Hispanic Whites, 14.9 percent of non-Hispanic Blacks, and 14.8 percent of Hispanics). After adjustment for demographics and comorbidities, Blacks and Hispanics were more than three times more likely to screen positive and two times more likely to be hospitalized relative to Whites, and Hispanics were two times more likely to die than Whites. Given the long-standing history of structural racism, residential segregation, and social risk in the US and their role as contributors to poor health, we propose and discuss the part these issues play as explanatory factors for our findings.

The Great Mask Debate: A Debate That Shouldn't Be a Debate at All.

BACKGROUND: Despite a rapidly growing and evolving literature, there continues to be a vigorous public debate about whether the community use of face coverings can mitigate the spread of COVID-19 ten months into the pandemic. OBJECTIVES: This article describes a semi-structured literature review of the use of face coverings to prevent the spread of coronaviruses and similar respiratory pathogens, with a focus on SARS-CoV-2 (COVID-19). METHODS: : The author conducted a semi-structured literature review using search terms "COVID19" or "SARS-CoV-2" crossed with "mask/s" or "face covering/s." Articles were evaluated through October 30, 2020 for inclusion, as were key references cited within the primary references and other references identified through traditional and social media outlets. RESULTS: There is strong evidence to support the community use of face coverings to mitigate the spread of COVID-19 from various laboratory, epidemiological, natural history, clinical, and economic studies, although there was only 1 high-quality published randomized controlled trial of this topic at the time of review. CONCLUSIONS: The evidence in favor of community face coverings to slow the spread of COVID-19 is strong. Although most of the benefit of wearing a face covering is conferred to the community and to bystanders, a face covering also can protect the wearer to some extent, both by reducing the risk of COVID-19 infection, and perhaps by reducing the severity of illness for those who contract a COVID-19 infection.

Element Abundances: A New Diagnostic for the Solar Wind.

We examine the different element abundances exhibited by the closed loop solar corona and the slow speed solar wind. Both are subject to the first ionization potential (FIP) effect, the enhancement in coronal abundance of elements with FIP below 10 eV (e.g., Mg, Si, Fe) with respect to high-FIP elements (e.g., O, Ne, Ar), but with subtle differences. Intermediate elements, S, P, and C, with FIP just above 10 eV, behave as high-FIP elements in closed loops, but are fractionated more like low-FIP elements in the solar wind. On the basis of FIP fractionation by the ponderomotive force in the chromosphere, we discuss fractionation scenarios where this difference might originate. Fractionation low in the chromosphere where hydrogen is neutral enhances the S, P, and C abundances. This arises with nonresonant waves, which are ubiquitous in open field regions, and is also stronger with torsional Alfvén waves, as opposed to shear (i.e., planar) waves. We discuss the bearing these findings have on models of interchange reconnection as the source of the slow speed solar wind. The outflowing solar wind must ultimately be a mixture of the plasma in the originally open and closed fields, and the proportions and degree of mixing should depend on details of the reconnection process. We also describe novel diagnostics in ultraviolet and extreme ultraviolet spectroscopy now available with these new insights, with the prospect of investigating slow speed solar wind origins and the contribution of interchange reconnection by remote sensing.

Drug Regimen Individualization for Attention-Deficit/Hyperactivity Disorder: Guidance for Methylphenidate and Dexmethylphenidate Formulations.

In 2000, the first biphasic modified-release (MR) formulation of methylphenidate (MPH) was approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). An immediate-release (IR) MPH pulse (22% of the dose) facilitates rapid onset of stimulant action, while the remaining MR portion of the dose provides for day-long duration of efficacy. A wide array of oral MR-MPH products has subsequently been approved that also allows for once-daily dosing, though each product is characterized by distinctive exposure time courses. This review compares each member of the current MPH armamentarium to assist in the rational selection of a specific MPH regimen for the individualized treatment of patients with ADHD. The IR portion of biphasic MPH formulations now ranges from 15%, 20%, 22%, 25%, 30%, and 37% IR-MPH, as well as a 50% IR-MPH product whose distinctly pulsatile time course closely resembles that of the pre-century "gold standard" twice-daily IR-MPH regimen. Further, transdermal, suspension, and orally disintegrating tablet products are now available to overcome any solid dosage form swallowing difficulties. Most of these formulations are racemic, though in 2001, a chiral switch drug IR-dexmethylphenidate (dexMPH) was approved, followed by biphasic MR-dexMPH (50% IR) in 2005. New U.S. Food and Drug Administration (FDA) partial area under the curve (pAUC) bioavailability metrics have improved discrimination between specific generic MR-MPH products. This has resulted in two Orange Book MR-MPH products being recoded from "AB" (i.e., meets necessary bioequivalence requirements) to "BX" (i.e., insufficient data to confirm bioequivalence). The metabolic drug interaction between MPH and alcohol, which increases MPH bioavailability, potentiates euphoric effects, and heightens abuse liability, is discussed. This review concludes with brief considerations of pharmacogenomic predictors of ADHD first-line drug selection, carboxylesterase allelic variants influencing interindividual MPH metabolism, and novel MPH formulations in the regulatory pipeline.

DeepSort: deep convolutional networks for sorting haploid maize seeds.

BACKGROUND: Maize is a leading crop in the modern agricultural industry that accounts for more than 40% grain production worldwide. THe double haploid technique that uses fewer breeding generations for generating a maize line has accelerated the pace of development of superior commercial seed varieties and has been transforming the agricultural industry. In this technique the chromosomes of the haploid seeds are doubled and taken forward in the process while the diploids marked for elimination. Traditionally, selective visual expression of a molecular marker within the embryo region of a maize seed has been used to manually discriminate diploids from haploids. Large scale production of inbred maize lines within the agricultural industry would benefit from the development of computer vision methods for this discriminatory task. However the variability in the phenotypic expression of the molecular marker system and the heterogeneity arising out of the maize genotypes and image acquisition have been an enduring challenge towards such efforts. RESULTS: In this work, we propose a novel application of a deep convolutional network (DeepSort) for the sorting of haploid seeds in these realistic settings. Our proposed approach outperforms existing state-of-the-art machine learning classifiers that uses features based on color, texture and morphology. We demonstrate the network derives features that can discriminate the embryo regions using the activations of the neurons in the convolutional layers. Our experiments with different architectures show that the performance decreases with the decrease in the depth of the layers. CONCLUSION: Our proposed method DeepSort based on the convolutional network is robust to the variation in the phenotypic expression, shape of the corn seeds, and the embryo pose with respect to the camera. In the era of modern digital agriculture, deep learning and convolutional networks will continue to play an important role in advancing research and product development within the agricultural industry.

Design of two series of 1:1 cocrystals involving 4-amino-5-chloro-2,6-dimethylpyrimidine and carboxylic acids.

Two series of a total of ten cocrystals involving 4-amino-5-chloro-2,6-dimethylpyrimidine with various carboxylic acids have been prepared and characterized by single-crystal X-ray diffraction. The pyrimidine unit used for the cocrystals offers two ring N atoms (positions N1 and N3) as proton-accepting sites. Depending upon the site of protonation, two types of cations are possible [Rajam et al. (2017). Acta Cryst. C73, 862-868]. In a parallel arrangement, two series of cocrystals are possible depending upon the hydrogen bonding of the carboxyl group with position N1 or N3. In one series of cocrystals, i.e. 4-amino-5-chloro-2,6-dimethylpyrimidine-3-bromothiophene-2-carboxylic acid (1/1), 1, 4-amino-5-chloro-2,6-dimethylpyrimidine-5-chlorothiophene-2-carboxylic acid (1/1), 2, 4-amino-5-chloro-2,6-dimethylpyrimidine-2,4-dichlorobenzoic acid (1/1), 3, and 4-amino-5-chloro-2,6-dimethylpyrimidine-2-aminobenzoic acid (1/1), 4, the carboxyl hydroxy group (-OH) is hydrogen bonded to position N1 (O-H...N1) of the corresponding pyrimidine unit (single point supramolecular synthon). The inversion-related stacked pyrimidines are doubly bridged by the carboxyl groups via N-H...O and O-H...N hydrogen bonds to form a large cage-like tetrameric unit with an R42(20) graph-set ring motif. These tetrameric units are further connected via base pairing through a pair of N-H...N hydrogen bonds, generating R22(8) motifs (supramolecular homosynthon). In the other series of cocrystals, i.e. 4-amino-5-chloro-2,6-dimethylpyrimidine-5-methylthiophene-2-carboxylic acid (1/1), 5, 4-amino-5-chloro-2,6-dimethylpyrimidine-benzoic acid (1/1), 6, 4-amino-5-chloro-2,6-dimethylpyrimidine-2-methylbenzoic acid (1/1), 7, 4-amino-5-chloro-2,6-dimethylpyrimidine-3-methylbenzoic acid (1/1), 8, 4-amino-5-chloro-2,6-dimethylpyrimidine-4-methylbenzoic acid (1/1), 9, and 4-amino-5-chloro-2,6-dimethylpyrimidine-4-aminobenzoic acid (1/1), 10, the carboxyl group interacts with position N3 and the adjacent 4-amino group of the corresponding pyrimidine ring via O-H...N and N-H...O hydrogen bonds to generate the robust R22(8) supramolecular heterosynthon. These heterosynthons are further connected by N-H...N hydrogen-bond interactions in a linear fashion to form a chain-like arrangement. In cocrystal 1, a Br...Br halogen bond is present, in cocrystals 2 and 3, Cl...Cl halogen bonds are present, and in cocrystals 5, 6 and 7, Cl...O halogen bonds are present. In all of the ten cocrystals, π-π stacking interactions are observed.

Genetically engineering better fungal biopesticides.

Microbial insect pathogens offer an alternative means of pest control with the potential to wean us off our heavy reliance on chemical pesticides. Insect pathogenic fungi play an important natural role in controlling disease vectors and agricultural pests. Most commercial products employ Ascomycetes in the genera Metarhizium and Beauveria. However, their utilization has been limited by inconsistent field results as a consequence of sensitivity to abiotic stresses and naturally low virulence. Other naturally occurring biocontrol agents also face these hurdles to successful application, but the availability of complete genomes and recombinant DNA technologies have facilitated design of multiple fungal pathogens with enhanced virulence and stress resistance. Many natural and synthetic genes have been inserted into entomopathogen genomes. Some of the biggest gains in virulence have been obtained using genes encoding neurotoxic peptides, peptides that manipulate host physiology and proteases and chitinases that degrade the insect cuticle. Prokaryotes, particularly extremophiles, are useful sources of genes for improving entomopathogen resistance to ultraviolet (UV) radiation. These biological insecticides are environmentally friendly and cost-effective insect pest control options. © 2017 Society of Chemical Industry.