Digital Commons Network^™

Quaternary Ammonia Compounds In Disinfectant Products: Evaluating The Potential For Promoting Antibiotic Resistance And Disrupting Wastewater Treatment Plant Performance, Zihao Lu, Anna K. Mahony, William A. Arnold, Christopher Marshall, Patrick J. Mcnamara

Civil and Environmental Engineering Faculty Research and Publications

Quaternary ammonium compounds (QACs) are a class of compounds that were widely used as disinfectants during the COVID-19 pandemic and continue to be used as disinfecting agents. After consumer usage, QAC concentrations are diluted in wastewater as they enter wastewater treatment plants. At sub-inhibitory concentrations, QACs may have unintended repercussions, including increased antibiotic resistance and inhibition of process performance in wastewater treatment plants. This review first summarizes how QACs inhibit bacteria and then highlights the mechanisms by which QACs can promote antibiotic resistance in general. Reported environmental concentrations of QACs are compared to concentrations that are suspected to impact antibiotic …

The Buzz Within: The Role Of The Gut Microbiome In Honeybee Social Behavior, J. B. Nguyen, Christopher Marshall, Chelsea N. Cook

Biological Sciences Faculty Research and Publications

Gut symbionts influence the physiology and behavior of their host, but the extent to which these effects scale to social behaviors is an emerging area of research. The use of the western honeybee (Apis mellifera) as a model enables researchers to investigate the gut microbiome and behavior at several levels of social organization. Insight into gut microbial effects at the societal level is critical for our understanding of how involved microbial symbionts are in host biology. In this Commentary, we discuss recent findings in honeybee gut microbiome research and synthesize these with knowledge of the physiology and behavior …

Schizachyrium Scoparium (C4) Better Tolerates Drought Than Andropogon Gerardii (C4) Via Constant Co2 Supply For Photosynthesis During Water Stress, Alina Dekirmenjian, Diego Montano, Michelle L. Budny, Nathan P. Lemoine

Biological Sciences Faculty Research and Publications

Climate change is dramatically altering global precipitation patterns across terrestrial ecosystems, making it critically important that we understand both how and why plant species vary in their drought sensitivities. Andropogon gerardii and Schizachyrium scoparium, both C₄ grasses, provide a model system for understanding the physiological mechanisms that determine how species of a single functional type can differ in drought responses, an issue remains a critical gap in our ability to model and predict the impacts of drought on grassland ecosystems. Despite its greater lability of foliar water content, previous experiments have demonstrated that S. scoparium maintains higher photosynthetic …

The Dichotomy Of Threat And Deprivation As Subtypes Of Childhood Maltreatment: Differential Functional Connectivity Patterns Of Threat And Reward Circuits In An Adult Trauma Sample, Michael T. Liuzzi, Farah Harb, Kevin Petranu, Ashley A. Huggins, E. Kate Webb, Jacklynn M. Fitzgerald, Jessica L. Krukowski, Tara A. Miskovich, Terri A. Deroon-Cassini, Christine L. Larson

Psychology Faculty Research and Publications

Background

Childhood maltreatment is associated with reduced activation of the nucleus accumbens, , a central region in the reward network, and overactivity in the amygdala, a key region in threat processing. However, the long-lasting impact of these associations in the context of later-life stress is not well understood. The current study explored the association between childhood threat and deprivation and functional connectivity of threat and reward regions in an adult trauma sample.

Methods

Trauma survivors (N = 169; mean age [SD] = 32.2 [10.3] years; female = 55.6%) were recruited from a level I trauma center. Two weeks after …

Seasonal Soil Moisture Thresholds Inhibit Bacterial Activity And Decomposition During Drought In A Tallgrass Prairie, Nathan P. Lemoine, Michelle L. Budny, Ethan Rose, Jane Lucas, Christopher Marshall

Biological Sciences Faculty Research and Publications

Soil moisture reductions during drought often inhibit soil microbial activity and inhibit decomposition rates by reducing microbial biomass or by altering microbial communities. Evidence suggests that soil water must drop below a critical threshold to inhibit microbial activity. Thus, it is likely that the seasonal timing of drought will determine the extent to which belowground processes are adversely impacted by drought. Specifically, the effects of drought might be minimal during cool, wet periods typical of late spring but dramatic during hot summer months with high evapotranspiration rates that lower soil moisture levels below the critical threshold. Here, we present results …

Self-Ambivalence: Naming A Contemporary Work–Family Problem That Has No Name, Jenny M. Hoobler, Courtney R. Masterson, Kristie M. Rogers

Management Faculty Research and Publications

As workers and family members, individuals ought to celebrate seemingly positive events (e.g., a promotion and the purchase of a home). Yet, the numerous identities that contemporary workers hold increase the likelihood of an event that is pleasant in one domain being problematic in another and more cognitively and affectively complex than anticipated. We theorize that these events are likely to prompt self-evaluations that are positive (“I'm a success!”) and negative (“I'm a failure.”) across one's identity set, with questions such as “Who have I become?” and “Is this who I ought to be?” The result is self-ambivalence, that is, …

Application Of The Adverse Childhood Experiences Framework To The Nicu, Kathryn J. Malin, Dorothy Vittner, Darilek Umber, Kelly Mcglothen-Bell, Allison Crawford, Rebecca Koerner, Britt Frisk Pados, Diana Cartegena, Jacqueline M. Mcgrath, Ashlee J. Vance

College of Nursing Faculty Research and Publications

Background:

Infants and families requiring neonatal intensive care unit (NICU) care often experience significant stress and trauma during the earliest period of the infant's life, leading to increased risks for poorer infant and family outcomes. There is a need for frameworks to guide clinical care and research that account for the complex interactions of generational stress, pain, toxic stress, parental separation, and lifelong health and developmental outcomes for infants and families.

Purpose:

Apply the Adverse Childhood Experiences (ACEs) framework in the context of the NICU as a usable structure to guide clinical practice and research focused on infant neurodevelopment outcomes …

Gwid: An R Package And Shiny Application For Genome-Wide Analysis Of Ibd Data, Soroush Mahmoudiandehkordi, Mehdi Maadooliat, Steven J. Schrodi

Mathematical and Statistical Science Faculty Research and Publications

Summary

Genome-wide identity by descent (gwid) is an R package developed for the analysis of identity-by-descent (IBD) data pertaining to dichotomous traits. This package offers a set of tools to assess differential IBD levels for the two states of a binary trait, yielding informative and meaningful results. Furthermore, it provides convenient functions to visualize the outcomes of these analyses, enhancing the interpretability and accessibility of the results. To assess the performance of the package, we conducted an evaluation using real genotype data derived from the SNPs to investigate rheumatoid arthritis susceptibility from the Marshfield Clinic Personalized Medicine Research Project.

Availability …

Benzoquinone Ligand-Enabled Ruthenium-Catalyzed Deaminative Coupling Of 2-Aminoaryl Aldehydes And Ketones With Branched Amines For Regioselective Synthesis Of Quinoline Derivatives, Krishna Prasad Gnyawali, Aldiyar Shakenov, Pandula T. Kirinde Arachchige, Chae S. Yi

Chemistry Faculty Research and Publications

The catalytic system generated in situ from the cationic Ru–H complex [(C₆H₆)(PCy₃)(CO)RuH]⁺BF₄– (1) with 2,3,4,5-tetrachloro-1,2-benzoquinone (L1) was found to be highly effective for promoting the deaminative coupling reaction of 2-aminoaryl aldehydes with branched amines to form 2-substituted quinoline products. The analogous deaminative coupling reaction of 2-aminoaryl ketones with branched amines led to the regioselective formation of 2,4-disubstituted quinoline products. A number of biologically active quinoline derivatives including graveolinine and a triplex DNA intercalator have been synthesized by using the catalytic method.

Synthesis And Evaluation Of 5-(Heteroarylmethylene)Hydantoins As Glycogen Synthase Kinase-3Β Inhibitors, Nicholas O. Schneider, Keandra Gilreath, Daniel J. Burkett, Martin St. Maurice, William A. Donaldson

Chemistry Faculty Research and Publications

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule inhibitors of GSK-3 have been reported. Phenylmethylene hydantoins are known to exhibit a wide range of inhibitory activities including for GSK-3β. A family of fourteen 2-heterocycle substituted methylene hydantoins (14, 17–29) were prepared and evaluated for the inhibition of GSK-3β at 25 μM. The IC50 values of five of these compounds was determined; the two best inhibitors …

The Association Between Vigour And Flexibility With Injury And Alertness During Shift Work, Lee Di Milia, Janet L. Barnes-Farrell, Rick A. Laguerre, Simon Folkard

Management Faculty Research and Publications

Models of shift work and health suggest that individual differences in circadian rhythm characteristics may moderate the relationship between night shift work and injury, but this argument has not been directly tested. In this study, we tested the efficacy of two circadian rhythm characteristics—vigour and flexibility—as moderators of the path between shift work and injury. In addition, we aimed to replicate the association between vigour, flexibility, and alertness by time of day, and the measurement properties of the Circadian Type Inventory. We recruited 401 healthcare workers from Australia and Great Britain. After controlling for confounding variables, the results showed that …

Synthesis And Evaluation Of 1,3-Disubstituted Imidazolidine-2,4,5-Triones As Inhibitors Of Pyruvate Carboxylase, Nicholas O. Schneider, Keandra Gilreath, Niel M. Henriksen, William A. Donaldson, Subhabrata Chaudhury, Martin St. Maurice

Biological Sciences Faculty Research and Publications

Substituted imidazolidinetriones (IZTs) have been identified as potent inhibitors of pyruvate carboxylase (PC) through an in silico screening approach. Alkyl 2-(2,4,5-trioxo-3-substituted imidazolidin-1-yl)acetates (6i–6r) are the most potent of the series, with IC50 values between 3 and 12 μM, and several IZTs demonstrate high passive permeability across an artificial membrane. IZTs are mixed-type inhibitors with respect to pyruvate and noncompetitive with respect to ATP. This class of inhibitors appears to be selective for PC. Inhibitors in the IZT series do not inhibit the metalloenzymes human carbonic anhydrase II and matrix metalloprotease-12, and they do not inhibit the related biotin-dependent enzyme, guanidine …

Bayesian Rare Variant Analysis Identifies Novel Schizophrenia Putative Risk Genes, Shengtong Han

School of Dentistry Faculty Research and Publications

The genetics of schizophrenia is so complex that it involves both common variants and rare variants. Rare variant association studies of schizophrenia are challenging because statistical methods for rare variant analysis are under-powered due to the rarity of rare variants. The recent Schizophrenia Exome meta-analysis (SCHEMA) consortium, the largest consortium in this field to date, has successfully identified 10 schizophrenia risk genes from ultra-rare variants by burden test, while more risk genes remain to be discovered by more powerful rare variant association test methods. In this study, we use a recently developed Bayesian rare variant association method that is powerful …

Immunohistochemical Analysis Of Dentigerous Cysts And Odontogenic Keratocysts Associated With Impacted Third Molars—A Systematic Review, Luis Eduardo Almeida, David Lloyd, Daniel Boettcher, Olivia Kraft, Samuel Zammuto

School of Dentistry Faculty Research and Publications

Objective: This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars.

Materials and Methods: A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as “dentigerous cysts”, “odontogenic keratocysts”, “immunohistochemistry”, “Ki-67”, and “p53” were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms …

(Wp 2024-01) Douglass North, New Institutional Economics, And Complexity Theory, John B. Davis, Mauro Boianovsky

Economics Working Papers

Douglass North was central to the emergence of New Institutional Economics. Less well known are his later writings where he became interested in complexity theory. He attended the second economics complexity conference at the Santa Fe Institute in 1996 on how the economy functions as a complex adaptive system, and in his 2005 Understanding the Process of Economic Change incorporated this thinking into his argument that market systems depend on how institutions evolve. North also emphasized in the 2005 book the role belief played in evolutionary processes, and drew on cognitive science, especially the famous ‘scaffolding’ idea of cognitive scientist …

Genetic Risk For Alzheimer’S Disease Alters Perceived Executive Dysfunction In Cognitively Healthy Middle-Aged And Older Adults, Sarah A. Evans, Elizabeth R. Paitel, Riya Bhasin, Kristy A. Nielson

Psychology Faculty Research and Publications

Background:

Subjective cognitive complaints (SCC) may be an early indicator of future cognitive decline. However, findings comparing SCC and objective cognitive performance have varied, particularly in the memory domain. Even less well established is the relationship between subjective and objective complaints in non-amnestic domains, such as in executive functioning, despite evidence indicating very early changes in these domains. Moreover, particularly early changes in both amnestic and non-amnestic domains are apparent in those carrying the Apolipoprotein-E ɛ4 allele, a primary genetic risk for Alzheimer’s disease (AD).

Objective:

This study investigated the role of the ɛ4 allele in the consistency between subjective …

Intrusive Traumatic Re-Experiencing Domain: Functional Connectivity Feature Classification By The Enigma Ptsd Consortium, Benjamin Suarez-Jimenez, Amit Lazarov, Sigal Zilcha-Mano, Xi Zhu, Yoojean Kim, Jacklynn M. Fitzgerald

Psychology Faculty Research and Publications

Background

Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity connectivity perspective.

Methods

Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium (n = 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data. We assessed the …

Editorial: Insights In Neurocognitive Aging And Behavior: 2022, Kristy A. Nielson, Annalena Venneri, Shin Murakami

Psychology Faculty Research and Publications

No abstract provided.

Exploring The Association Between Structural Racism And Mental Health: Geospatial And Machine Learning Analysis, Fahimeh Mohebbi, Amir Masoud Forati, Lucas Torres, Terri A. Deroon-Cassini, Jennifer Harris, Carissa W. Tomas, John R. Mantsch, Rina Ghose

Psychology Faculty Research and Publications

Background:

Structural racism produces mental health disparities. While studies have examined the impact of individual factors such as poverty and education, the collective contribution of these elements, as manifestations of structural racism, has been less explored. Milwaukee County, Wisconsin, with its racial and socioeconomic diversity, provides a unique context for this multifactorial investigation.

Objective:

This research aimed to delineate the association between structural racism and mental health disparities in Milwaukee County, using a combination of geospatial and deep learning techniques. We used secondary data sets where all data were aggregated and anonymized before being released by federal agencies.

Methods:

We …

Pseudomonas Mosselii Improves Cold Tolerance Of Asian Rice (Oryza Sativa L.) In A Genotype-Dependent Manner By Increasing Proline In Japonica And Reduced Glutathione In Indica Varieties, Nasim Maghboli Balasjin, James Maki, Michael Schläppi

Biological Sciences Faculty Research and Publications

Cold stress is an important factor limiting rice production and distribution. Identifying factors that contribute to cold tolerance in rice is of primary importance. While some plant specific genetic factors involved in cold tolerance have been identified, the role of the rice microbiome remains unexplored. In this study, we evaluated the influence of plant growth promoting bacteria (PGPB) with the ability of phosphate solubilization on rice cold tolerance and survival. To reach this goal, inoculated and uninoculated 2-week-old seedlings were cold stressed and evaluated for survival and other phenotypes such as electrolyte leakage (EL) and necessary elements for cold tolerance. …

It’S A Trap?! Escape From An Ancient, Ancestral Sex Chromosome System And Implication Of Foxl2 As The Putative Primary Sex-Determining Gene In A Lizard (Anguimorpha; Shinisauridae), Brendan J. Pinto, Stuart V. Nielsen, Kathryn A. Sullivan, Ashmika Behere, Shannon E. Keating, Mona Van Schingen-Khan, Truong Q. Nguyen, Thomas Ziegler, Jennifer Pramuk, Melissa A. Wilson, Tony Gamble

Biological Sciences Faculty Research and Publications

Although sex determination is ubiquitous in vertebrates, mechanisms of sex determination vary from environmentally to genetically influenced. In vertebrates, genetic sex determination is typically accomplished with sex chromosomes. Groups like mammals maintain conserved sex chromosome systems, while sex chromosomes in most vertebrate clades are not conserved across similar evolutionary timescales. One group inferred to have an evolutionarily stable mode of sex determination is Anguimorpha, a clade of charismatic taxa including monitor lizards, Gila monsters, and crocodile lizards. The common ancestor of extant anguimorphs possessed a ZW system that has been retained across the clade. However, the sex chromosome system in …

Differential Conservation And Loss Of Chicken Repeat 1 (Cr1) Retrotransposons In Squamates Reveal Lineage-Specific Genome Dynamics Across Reptiles, Simone M. Gable, Nicholas A. Bushroe, Jasmine M. Mendez, Adam Wilson, Brendan J. Pinto, Tony Gamble, Marc Tollis

Biological Sciences Faculty Research and Publications

Transposable elements (TEs) are repetitive DNA sequences which create mutations and generate genetic diversity across the tree of life. In amniote vertebrates, TEs have been mainly studied in mammals and birds, whose genomes generally display low TE diversity. Squamates (Order Squamata; including ∼11,000 extant species of lizards and snakes) show as much variation in TE abundance and activity as they do in species and phenotypes. Despite this high TE activity, squamate genomes are remarkably uniform in size. We hypothesize that novel, lineage-specific genome dynamics have evolved over the course of squamate evolution. To understand the interplay between TEs and host …

Efficient Synthesis Of Thiazole-Fused Bisnoralcohol Derivatives As Potential Therapeutic Agents, Subrata Roy, Hansa Raj Kc, Sanjay Adhikary, Alexander N. Erickson, Mohammad Abrar Alam

Chemistry Faculty Research and Publications

Thiazole derivatives are known for a wide range of therapeutic properties. Bisnoralcohol is an inexpensive natural product obtained by the biodegradation of sterols. This article describes an efficient synthesis of a library of thiazole-fused bisnoralcohol derivatives. These novel compounds have been studied for their antineoplastic and antibacterial properties, which led to the discovery of hit compounds with therapeutic potential. The antibacterial compound is noncytotoxic and nonhemolytic against cancer cell lines and sheep red blood cells, respectively. Several of the antineoplastic compounds showed activity against human cancer cell lines with growth inhibition at submicromolar concentration.

Anticancer Drugs Of Lysine Specific Histone Demethylase-1 (Lsd1) Display Variable Inhibition On Nucleosome Substrates, Dulmi Senanayaka, Danyun Zeng, Emre Deniz, Indunil K. Priyankara, Joceline Helmbreck, Owen Schneider, Aashay Mardikar, Aykut Uren, Nicholas J. Reiter

Chemistry Faculty Research and Publications

Lysine specific demethylase-1 (LSD1) serves as a regulator of transcription and represents a promising epigenetic target for anticancer treatment. LSD1 inhibitors are in clinical trials for the treatment of Ewing’s sarcoma (EWS), acute myeloid leukemia, and small cell lung cancer, and the development of robust inhibitors requires accurate methods for probing demethylation, potency, and selectivity. Here, the inhibition kinetics on the H3K4me2 peptide and nucleosome substrates was examined, comparing the rates of demethylation in the presence of reversible [CC-90011 (PD) and SP-2577 (SD)] and irreversible [ORY-1001 (ID) and tranylcypromine (TCP)] inhibitors. Inhibitors were also subject to viability studies in three …

Female Athletes With Better Psychological Readiness Are At Higher Risk For Second Acl Injury After Primary Acl Reconstruction, Ryan Zarzycki, Kathleen Cummer, Elanna Arhos, Matthew Failla, Jacob J. Capin, Angela H. Smith, Lynn Snyder-Mackler

Physical Therapy Faculty Research and Publications

Background: Approximately 1 in 4 athletes returning to sports will sustain a second anterior cruciate ligament (ACL) injury. Psychological factors related to kinesiophobia, confidence, and psychological readiness are associated with second ACL injury; however, the evidence is conflicting.

Hypothesis: Athletes who sustain a second ACL injury (ie, graft rupture or contralateral ACL rupture) within 2 years of ACL reconstruction (ACLR) would have greater kinesiophobia, less confidence, and lower psychological readiness prior to return to sport (RTS) compared with athletes who do not sustain a second ACL injury.

Study Design: Secondary analysis of a prospective randomized trial.

Level …

Age-Related Development Of Bilateral Coordination Of The Upper Limbs In Children And Adolescents, Samuel Nemanich, Sheila M. Schindler-Ivens

Physical Therapy Faculty Research and Publications

Bilateral coordination of the upper limbs (UL) is important for activities of daily living and physical activities. Motor coordination improves from childhood through adolescence. However, age-coordination trajectories for bilateral UL movements are not well-established, and it is unclear if bimanual coordination develops slower than unilateral coordination. In this study we examined age-related changes in UL coordination from childhood to late adolescence. Typically-developing children (N = 29, aged 7–17 years) performed unilateral and bilateral, antiphase cycling tasks with their ULs. Variations in cycling velocity and interlimb phase errors were computed as measures of coordination. Linear regression was used to examine …

A Qualitative Analysis Of Ableist Microaggressions, Jennifer M. Cook, Melissa Deroche, Lee Za Ong

College of Education Faculty Research and Publications

The phenomenon of microaggressions is well established within the counseling literature, particularly as it relates to race, ethnicity, gender, and affectual orientation. However, research related to disability or ableist microaggressions is still in its infancy, so counseling professionals have limited information about experiences of disability and ableist microaggressions. The purpose of this qualitative content analysis was to describe participants’ self-reported experiences with ableist microaggressions. Participants (N = 90) had a diagnosed disability and the majority (91.11%) identified as having two or more nondominant identities beyond their disability. We report two categories and 10 themes. While participants were part of …

Ableist Microaggressions, Disability Characteristics, And Nondominant Identities, Melissa Deroche, Lee Za Ong, Jennifer M. Cook

College of Education Faculty Research and Publications

Microaggressions are commonplace overt and covert forms of discrimination that convey disparaging messages to individuals who hold marginalized identities, including people with disabilities (PWD). Although PWD are a prevalent nondominant identity group in the United States, little is known about the occurrence of ableist microaggressions in this culturally diverse community, including how ableist microaggressions are experienced based on disability characteristics and other nondominant identities. A sample consisting of 201 PWD completed an electronic survey that examined the occurrence of ableist microaggressions based on visibility of disability, type of disability, and nondominant sociocultural identities. We found that PWD have a moderate …

A Scoping Review On Mobile Health Technology For Assessment And Intervention Of Upper Limb Motor Function In Children With Motor Impairments, Md Raihan Mia, Sheikh Iqbal Ahamed, Alissa V. Fial, Samuel Nemanich

Computer Science Faculty Research and Publications

Upper limb (UL) motor dysfunctions impact residual movement in hands/shoulders and limit participation in play, sports, and leisure activities. Clinical and laboratory assessments of UL movement can be time-intensive, subjective, and/or require specialized equipment and may not optimally capture a child's motor abilities. The restrictions to in-person research experienced during the COVID-19 pandemic have inspired investigators to design inclusive at-home studies with child participants and their families. Relying on the ubiquity of mobile devices, mobile health (mHealth) applications offer solutions for various clinical and research problems. This scoping review article aimed to aggregate and synthesize existing research that used health …

Research Priorities For Childhood Apraxia Of Speech: A Long View, Jenya Iuzzini-Seigel

Speech Pathology and Audiology Faculty Research and Publications

This article introduces the Journal of Speech, Language, and Hearing Research Special Issue: Selected Papers From the 2022 Apraxia Kids Research Symposium. The field of childhood apraxia of speech (CAS) has developed significantly in the past 15 years, with key improvements in understanding of basic biology including genetics, neuroscience, and computational modelling; development of diagnostic tools and methods; diversity of evidence-based interventions with increasingly rigorous experimental designs; and understanding of impacts beyond impairment-level measures. Papers in this special issue not only review and synthesize the some of the substantial progress to date but also present novel findings addressing critical research …