Borrelia-specific antibodies in serum and Borrelia-specific AI in LB investigations being made during 2017 in Jönköping County, Sweden. Medical records of 610 patients with detectable anti-Borrelia antibodies in serum (IgM and/or IgG) and 15 patients with elevated Borrelia-specific AI were retrospectively scrutinized, and the compliance to current European recommendations was assessed. Among the 610 patients, only 30% were tested according to the European recommendations. Within this group of tests taken correctly, 50% of the LB diagnoses in patients with isolated IgM reactivity in serum were retrospectively assessed as incorrect (LB unlikely). Three pediatric patients with clinical and laboratory findings suggestive of Lyme neuroborreliosis (LNB) had elevated IgM AI alone. Serological testing without distinct clinical signs/symptoms consistent with LB contributes to most misdiagnoses. Isolated IgM positivity in serum shows limited clinical value and needs further assessment before being reported by the laboratory. Detection of IgM in combination with IgG antibodies in serum shows no clinical enhancement for correct LB diagnosis compared to isolated IgG positivity. However, Borrelia-specific IgM AI may be important for sensitivity in early LNB.Interpretation of serological findings in suspected Lyme borreliosis (LB) may be challenging and IgM reactivities in serum are often unspecific . There is a risk for overdiagnosis of LB, inadequate use of antibiotics, and potential delay of proper diagnosis. In this study, we evaluated the diagnostic value of IgM analysis in serum and IgM antibody index (AI) in LB diagnosis. This was a retrospective observational study regarding  Borrelia burgdorferi sensu lato complex. The pathology is due to an activation of the host’s innate and adaptive immune responses, [Borrelia-specific antibodies. The activation of the immune system and the relative organotropism of the bacterium may lead to different but specific clinical manifestations [Borrelia-specific CSF/serum antibody index (AI) as an indication of intrathecally produced Borrelia-specific antibodies [Lyme borreliosis (LB) is a tick-borne infection caused by bacteria of the sponses,  resultinstations , 2. Erytstations , 3. The stations , 4 For dstations , 4, 5 Intibodies .Borrelia-specific antibodies in the population can be over 20% in certain areas, [The interpretation of the serologic findings (IgM and IgG) may be complicated. There are several limitations regarding the analysis of these antibodies –4. For en areas, , 6, 7 thn areas, , 9.Borrelia-specific antibodies in situations where testing is not recommended, which causes a high false positive rate due to the significant seroprevalence [The clinical manifestations of LB are described in the current European case definitions in order to facilitate clinical diagnosis and enhance the highest pre-test probabilities and predictive values.  Despite evalence . Anotherevalence , IgM is evalence . AppreheThe main objective of this study was to evaluate the diagnostic value of IgM analysis in serum in LB diagnosis as well as the value of IgM AI in diagnosis of LNB. The specific aims of this study were (i) to assess the proportion of serologic LB analyses ordered in adherence to current European case definitions and recommendations, (ii) to evaluate the diagnostic value of IgM in serum in LB diagnosis and of IgM AI in diagnosis of LNB, and (iii) to evaluate the accuracy of the LB diagnoses made by the clinicians after receiving the serologic results in order to assess whether a positive IgM result was helpful or harmful for the diagnosis being made.Borrelia-specific antibodies in serum and intrathecal AI in LB and LNB investigations being made during the year 2017 in Jönköping County, Sweden. There was a total number of 4428 Borrelia-specific antibody tests in serum analyzed during this year  were taken from a total of 643 individual patients, of which we had to exclude 33 patients due to inaccessible medical records. Among these 610 patients included, some were tested repeatedly (n = 73), in which case the first positive test result during 2017 was regarded as the primary test, and any following tests taken within 6 months were only considered for evaluating potential seroconversion and not as a primary test, unless it was obvious from the medical records that the test was related to a new episode of illness with new symptoms. The patients (n = 610) with positive test results were divided into three separate groups depending on the seropositivity pattern  . We selected all patients with positive Borrelia-specific CSF/serum AI (n = 15) and divided them into similar groups according to their positive AI (IgM AI and/or IgG AI). These groups were similarly assessed by their medical records regarding symptoms, present CSF pleocytosis, LNB diagnosis given, antibiotic treatment, and if they had Borrelia-specific antibodies detected in serum as well. Pleocytosis was defined as total white blood cell count > 5 × 106/L in CSF.In addition, we looked into all analyses of LNB performed on paired serum and CSF samples during 2017 . The cut-off levels used were 10 U/mL for IgG and 2 U/mL for IgM. The IgM cut-off had after evaluation been adapted to local seroprevalence conditions (the cut-off suggested by the manufacturer is 1 U/mL). Seroconversion was defined as Borrelia-specific antibodies being undetectable in the first sample but positive in a second sample (if available). Significant elevation of antibodies was in this study defined as a 2-fold increase or more of the antibody level ). The authors are aware that an increase of the OD above the linear range of the assay is not possible to assess.Patient samples had been analyzed for Borrelia-specific AI was determined by the IDEIA Lyme neuroborreliosis kit (IgM and IgG) , which is a flagella antigen-based enzyme linked immunosorbent assay. A Borrelia-specific AI > 0.3 was considered as a positive result.For paired serum and CSF samples, the Borrelia serology (IgM and/or IgG), 183/610 (30 %) were tested according to the European clinical recommendations  had EM and should not have been serologically tested. After excluding patients with EM, 72/353 (20.4%) of the remaining patients received a LB diagnosis (Table We found that 427/610 (70 %) patients were tested for Almost every patient who received a LB diagnosis was treated with antibiotics; 95/96 (99.0 %) among the patients where tests were taken according to recommendations and 71/72 (98.6 %) in the group of patients where tests were taken outside the current recommendations.n = 6, IgM AI n = 3, IgG and IgM AI n = 6) and CSF pleocytosis were present in all but in 3 patients, all within the IgG AI group  patients had an elevated AI , but this has not been investigated here. This finding is similar to what has been shown in other studies where as much as up to 82% of tests had been taken in contradiction with current guidelines [In this study, we evaluated the clinical impact of IgM reactivities in idelines , 11 MostWhen looking at the results of the tests taken according to recommendations, there is no clinical enhancement for dual IgM and IgG positivity compared to isolated IgG positivity to be seen when it comes to establishing a correct diagnosis Fig. . Hence, Borrelia-specific IgG levels were present.Furthermore, the proportion of patients receiving a LB diagnosis was higher in the group with both IgM and IgG positivity compared to the group with isolated IgG positivity, and as seen during our review of the patients’ medical records, clinicians tend to believe that a present IgM response is required for an active infection, whereas the lack of IgM positivity rather speaks against an active infection. In several cases with IgG positivity alone, the physicians had decided not to treat the patient with antibiotics even though the LB diagnosis seemed quite obvious with specific symptoms and correct serologic findings. As an example, ACA was ruled out in a patient because the lack of IgM antibodies even though a long-standing skin rash and high Borrelia-specific antibodies should be investigated.Isolated IgM positivity in serum is quite rare in the group of patients tested in accordance with the recommendations. Isolated IgM showed very limited clinical value and needs further assessment in order to offer any guidance at all. The analyzing laboratory should either have a routine of confirming specificity with an immunoblot, or instead recommend a follow-up test 4– weeks later. In suspected LNB cases, a lumbar puncture should be performed and the presence of intrathecally produced When analyzing the borrelia tests taken without proper indication, we noticed the same pattern regarding the presence of IgM positivity and its effect on whether a LB diagnosis was made or not. Clinicians connect a positive IgM with an active infection and are more inclined to interpret it as an actual and on-going infection, regardless of the lack of specific symptoms. The result is that patients acquire a very doubtful diagnosis and receive treatment with antibiotics on incorrect grounds. Isolated IgM reactivities in the group of patients tested outside current recommendations, EM patients excluded, were more frequently assessed as unspecific in this study.In this perspective, IgM reactivities, as well as lack of them, seem to be more harmful than helpful in LB diagnosis, causing both over- and underdiagnosis, overuse of antibiotics and delay of proper diagnosis and treatment. For the patients, delay of correct diagnosis may be associated with prolonged suffering and anxiety, and for the healthcare system, with increased costs.Borrelia-specific CSF/serum AI, 3/11 confident diagnoses of LNB would have been missed if IgM AI analyses had not been performed. All three patients were children, two with symptoms of meningitis and one with a one sided facial palsy, and all had elevated IgM AI only. Thus, determination of Borrelia-specific IgM AI increased the diagnostic sensitivity for the IDEIA Lyme neuroborreliosis assay. Furthermore, two of these three children had no detectable levels of Borrelia-specific antibodies in serum, which underscores the necessity of performing CSF analysis in suspected LNB cases.In our patients with paired serum and CSF analyses, we noticed that among 15 patients with positive Our findings suggest that IgM testing in serum is potentially more harmful than helpful in LB diagnosis. However, the main problem seems to be the large amount of tests taken outside the current recommendations, i.e., with very low pre-test-probability, and our suspicion is that many clinicians lack the proper knowledge regarding how to use and interpret serologic findings in LB diagnosis, and have very high faith in especially IgM positivity. Based on our assessments in this study, our conclusion is that IgM testing in serum causes more unreliable diagnoses and mistreatments, and should therefore be excluded in future testing, except when the analysis is paired with a simultaneous CSF analysis. Perhaps, another possibility could be that the laboratory would demand explicit and distinct clinical information on the referral and only perform IgM testing in cases where it actually could be useful, such as early LNB, LC, and BL as suggested by Dessau et al . At leasBorrelia-specific AI may be important for sensitivity in early LNB. However, the extensive testing for Borrelia-specific antibodies in contravention of current recommendations appears to be a major factor complicating interpretation of serological results and contributing to misdiagnosis and unfounded use of antibiotics.Based on our findings, we conclude that IgM analysis in serum is of limited diagnostic value for LB diagnosis since no increase of sensitivity is gained compared to IgG testing alone. In addition, specificity issues may lead to misinterpretation and overdiagnosis of LB. In contrast, analysis of


ABSTRACT IMPACT: This work aims to identify best practices for university-based asset development programs to improve commercialization throughput, which in turn will drive innovation in the biomedical space and directly contribute to improved human health. OBJECTIVES/GOALS: University technology transfer exhibits a high rate of failure, often due to a lack of researcher experience or early-stage financial capital. The LEAP program at Washington University (WUSTL) was created to address these needs. The goal of this study is to assess the performance of LEAP against similar gap funds and further improve program operations. METHODS/STUDY POPULATION: The goals of LEAP are achieved by providing university inventors with individualized consulting and feedback from industry experts, as well as awarding funding to the most promising projects. To determine whether these activities are impactful, we distributed an awardee report form to collect data on all funded LEAP projects, and then combined the results with project registration information. We also collected records Office of Technology Management, including invention disclosures, licenses, and startup creations. The resulting dataset was used to calculate program metrics and then evaluated against comparable gap funds. Sentiment data from participant surveys were also analyzed to assess perceived program value and knowledge transfer. RESULTS/ANTICIPATED RESULTS: As of the Sp2020 cycle, LEAP has funded 76 projects. Resubmitted projects had a funding rate of 52%, vs. 34% for new projects. Of the startups founded off of WUSTL intellectual property since 2016, nearly two-thirds had previously participated in LEAP. Funded LEAP projects also had a 29% licensing rate, which is comparable to similar gap funds. Lastly, participants self-reported an increase in knowledge across a range of commercialization areas. DISCUSSION/SIGNIFICANCE OF FINDINGS: The increased repeat funding rate and self-reported knowledge suggest that LEAP is impactful in building commercialization proficiency. The licensing rate and prevalence of LEAP projects in WUSTL startups also indicate that LEAP is indeed promoting tech transfer. Together, these results suggest that LEAP could be a model for other institutions.


ARID1A) variation is a distinct genetic entity in CCA, getting mounting concerns recently. Here, we comprehensively reviewed the clinical significance and molecular mechanisms of ARID1A alterations in CCA. Based on the independent data derived from 29 relevant studies, the variation rate of ARID1A in intrahepatic and extrahepatic CCA is reported at 6.9–68.2% and 5–55%, respectively. Most of the included studies  suggest that ARID1A serves as a tumor suppressor in CCA. ARID1A variation may be an important prognostic indicator to predict disease mortality, metastasis, and recurrence in patients with CCA. Multifactorial molecular mechanisms are involved in the relationship between ARID1A variations and the pathogenesis and pathophysiology of CCA, including disruption of the cell cycle, chromatin remodeling, oxidative stress damage, DNA hypermethylation, and the interaction of multiple genes being affected. This review describes that ARID1A variation might be a potential diagnostic and prognostic biomarker for CCA. Future diagnoses and treatments targeting ARID1A hint towards a precision medicine strategy in the management of CCA.Cholangiocarcinoma (CCA), a high mortality malignant carcinoma characterized by advanced disease and frequent recurrence, constitutes a major challenge for treatment and prognosis. AT-rich interaction domain 1A ( Cholangiocarcinoma (CCA) is the second most frequently diagnosed primary liver malignancy, accounting for 10–20% of primary hepatic carcinomas, and representing 3% of all gastrointestinal tumors . In addiSWI/SNF) chromatin-remodeling complex may be one of the most commonly mutated genes in multiple malignancies. SWI/SNF chromatin remodeling complex is involved in transcription and DNA replication and repair (ARID1A) is the most frequently mutated SWI/SNF gene across a broad spectrum of human cancers, which facilitates access of proteins to DNA  OR (B120)) OR (BAF250)) OR (BAF250a)) OR (BM029)) OR (C1orf4)) OR (CSS2)) OR (ELD)) OR (MRD14)) OR (OSA1)) OR (P270)) OR (SMARCF1)) OR (hELD)) OR (hOSA1)). Additional studies were detected by manual inspection of reference lists in the relevant publications. The following information was extracted based on a data collection form, including the first authors’ names of the included studies, publication year, country, type of cholangiocarcinoma, ARID1A variations presented with cases and percentage, effect of ARID1A on CCA, and clinical implications or biological functioning of ARID1A.Four databases, i.e., MEDLINE (PubMed), EMBASE (OVID), Cochrane Library, and PsychINFO were systematically searched to screening the related studies prior to April 1, 2021. Only studies reporting with English language were included. The searching strategy employed for identifying the eligible studies in PubMed databases was: ((((((((((((((“Cholangiocarcinoma”[Mesh]) OR (Cholangiocarcinomas)) OR (Cholangiocellular Carcinoma)) OR ) OR ) OR (Cholangiocellular Carcinomas)) OR (Extrahepatic Cholangiocarcinoma)) OR ) OR ) OR (Extrahepatic Cholangiocarcinomas)) OR (Intrahepatic Cholangiocarcinoma)) OR ) OR ) OR (Intrahepatic Cholangiocarcinomas)) AND , tissue microarrays, western-blot, quantitative real-time reverse transcription-polymerase chain reaction, and chromatin immunoprecipitation. The anti-ARID1A antibodies were inconsistent among different studies, including different antigenic determinant , various antibody manufacturer , diverse dilution rate , and the different cut off that used for defining “positive vs. negative” samples. As shown in ARID1A variations among the 29 studies ranged from 5 to 68.2%. Only one study reported that ARID1A variants might serve as a cancer-promoting gene in CCA, while the remaining 28 included studies indicated ARID1A variants might be a suppressor in CCA development and progression. Four studies have provided the data of the type of ARID1A variants in CCA. There are two types of ARID1A variants, including mutant and wild type , while a mutant one is defined as loss of ARID1A expression or low expression of ARID1A. In Namjan et al.’s study  of ARID1A were significantly associated with loss of ARID1A expression in CCA. In a cohort of 209 CCA cases  and the types of mutations, including 3 non-sense mutations, 1 frameshift insertion-deletion, and 2 missense mutations. ARID1A variations in Simbolo et al.’s study , ICC, and ECC was 15–55%, 6.9–68.2%, and 5–55%, respectively. According to previous reports, the highest ARID1A variant rate was found in ovarian clear cell carcinoma, up to 46–57% . The above results indicate that there might be a pivotal pathogenic link between the high frequency of ARID1A variations and CCA development.In this comprehensive review, we have summarized all the evidence relating to the o 46–57% . And then et al.  comparedARID1A mutation rates and expression level that observed between different studies could be due to multiple factors, including distinct demographic characteristics , different types  and disease states (early or advanced CCA), specific anti-ARID1A antibodies and measurements for assessing the ARID1A expression , and various co-present or targeted proteins being affected by ARID1A. Based on this evidence, an international multicenter with a large sample size and well-designed study is still needed to better illuminate the relationship between ARID1A mutations and CCA development, which is crucial for future strategies of CCA treatment.The differences in ARID1A in CCA tissues, the remaining 28 studies (96.6%) suggested that the expression of ARID1A in CCA was low or absent. In other words, only one study concluded that ARID1A plays an oncogenic role, while the remaining studies suggest that ARID1A serves as a tumor suppressor and this is consistent with the ARID1A functions in other cancer types, including ovarian clear cell, gastric, pancreatic, colon, breast, lung, bladder, and renal cancer  tumor tissues presented with positive immunohistochemical staining in ICC. However, the majority of the clinical studies showed that decreased/absent ARID1A correlated with worse stage and prognosis in patients with ICC  in CCA . The median overall survival of ICC in mutation and wild type of ARID1A was 14 and 52 months, respectively (P = 0.012). Yang et al. (ARID1A variation was detected in 19/57 (26.3%) ICC patients and found that low ARID1A expression was dramatically correlated with worse OS . In addition, they also found that ARID1A was associated with tumor nodules, vein invasion, and tumor recurrence status in CCA. Conci et al.  of CCA . They further found that ARID1A variation was associated with a local recurrence in 43% of cases. A study . In a study in Thailand . Sasaki et al. -pattern of CCA. Yoshino et al. . Wagner et al. demonstrated that suppressor ARID1A protein loss correlated with lower OS significantly loss of ARID1A protein expression is significantly correlated with lower OS when compared to the intact expression pattern . The above studies that confirmed the prognostic value of ARID1A variations in CCA were correlated to the ARID1A deficiency or low expression. However, Bi et al.  as well as disease recurrence , but such prognostic effects were based on high expression of ARID1A. Notably, an opposite effect played by ARID1A in CCA was found in Bi et al.’s study when compared to the remainder 28 included studies. Since Bi et al. have employed immunohistochemistry (IHC) to evaluate ARID1A variations rather than the sequencing analysis which was commonly used by other investigators, experimental and technical challenges  might play role in the inconsistent effect of ARID1A identified in different studies. For example, in each of the seven studies conducted by IHC . Lowery et al. . Similarly, Ma et al. (ARID1A expressions were not significantly associated with DFS and OS in patients with ICC (P > 0.05). Xu et al. . On the contrary, those studies reported the ARID1A variations rate over 20% were more likely to more likely to identify a poor prognostic significance for ARID1A variations in CCA  in CCA cells. ARID1A-knockout in CCA cells lines promotes migration, invasion, and sphere formation activity, which might be correlated to transcriptional suppression of ALDH1A1 expression with decreasing histone H3K27 acetylation. A study conducted by Sasaki et al. -positivity. Farshidfar et al. (ARID1A exhibited DNA hypermethylation and decreased expression of the isocitrate dehydrogenase (IDH) in the mutant subtype of CCA.Since a causal relationship between igenesis . Inactivn in CCA . Chan-onn in CCA  reportedo et al.  indicatei et al.  suggestsA repair . Alteratwith ECC . Both TPy in CCA . It was am genes . Therefoi et al.  developer et al.  showed tARID1A (20%) and TP53 (17%) were among the most common oncogenic alterations in CCA. In line with this finding, Zhang et al.  which could be involved in CCA development. For example, Jiao et al. , which was considered as the frequently targeted pathway in CCA, were somatically altered in almost half of the intrahepatic CCA cases. In 2013, Chan-on et al. , whereas these tumors had lost ARID1A expression suggesting that loss of ARID1A expression might represent an alternative (to ARID1A genomic variations) mechanism for ARID1A-driven carcinogenesis in CCA, and this could also be an alternative to KRAS mutations-driven CCA development. In line with this, Namjan et al.  that enhance cellular proliferation and anti-apoptotic processes. However, further comprehensive researches are still warranted to better elucidate the underlying mechanisms of CCA development initiated by ARID1A variations.In summary, ARID1A variations and CCA at both clinical and biological levels. However, some inherent limitations should be noted. First, the variation rate of ARID1A in CCA diverse in different studies, ranging from 5 to 68.2%. Different cancer types and stages, study design, sample size, geographical areas, gender, and age could all be partly responsible for this heterogeneity. Second, the prognostic significance of ARID1A in CCA is still controversial among the included studies. Nevertheless, we do not perform a meta-analysis for these studies due to due to unavailability of sufficient relevant data  in most of the studies. Third, the molecular mechanisms for the involvement of ARID1A variants in CCA tumorigenesis remain to be explored. In addition to ARID1A alteration, some other common contributors in cancer development, such as tumor microenvironment and tumor immunity, might also play roles in the pathomechanism of CCA, which should be further investigated.To our knowledge, this is the first study for conducting a comprehensive review to summarize all the evidence of the relationship between ARID1A variations in CCA cases are diverse in different studies, ranging from 5 to 68.2%. A higher ARID1A variation rate has been identified in the ICC subgroup when compared to the ECC subgroup (6.9–68.2% vs. 5–55%). Excepting for one study indicating the carcinogenic functions for ARID1A, the remaining 28 included studies suggest that ARID1A is a tumor suppressor in CCA. Though more studies show that loss or low ARID1A expression is significantly correlated with worse survival and recurrence in CCA, several studies do not support these prognostic values of ARID1A. Multifactorial mechanisms are involved in the pathogenesis of CCA caused by ARID1A variations. More investigations are necessary to validate the prognostic significance of ARID1A variations and to identify its molecular mechanism in CCA development.This review has shown SZ, YX, and WW contributed to conceive and design the study. YW and PW performed the systematic searching. HJ and JZ extracted the data. SZ and JZ wrote the manuscript. YX and WW supervised the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the Welfare Technology Applied Research Project of Zhejiang Province (LGC20H200004), Reagent Project of Taizhou City, Zhejiang Province (ID: 1901ky38), the High-level Hospital Construction Research Project of Maoming People’s Hospital, and the Technology Planning Project of Taizhou City, Zhejiang Province (ID: 20ywb40).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Scholars largely met goals for academic products, achieving a combined total of 65 peer-reviewed presentations and nine empirical publications. Eight scholars completed the 2-year program; one undergraduate scholar received her degree early and the postdoctoral fellow accepted a tenure-track position at another university following one year of training. Scholars highly rated UHAND’s programming and their mentors’ competencies in training scholars for research careers. Additionally, we discuss lessons learned that may inform future training programs.Black and Hispanic adults are disproportionately affected by cancer incidence and mortality, and experience disparities in cancer relative to their White counterparts in the US. These groups, including women, are underrepresented among scientists in the fields of cancer, cancer disparities, and cancer care. The “UHAND” Program is a partnership between institutions (University of Houston and The University of Texas MD Anderson Cancer Center) aiming to build the capacity of underrepresented and racial/ethnic minority student “scholars” to conduct research on eliminating cancer inequities by reducing social and physical risk factors among at-risk groups. Here, we examine the outcomes of the UHAND Program’s first scholar cohort . Data collection included baseline, mid-program, and exit surveys; program records; and monthly scholar achievement queries. From baseline to exit, scholars significantly increased their research self-efficacy ( The underrepresentation of women and individuals identifying as members of racial/ethnic minority groups in cancer disparities research and cancer care is well known ,2, as arThere are many benefits of training a diverse workforce to address cancer and cancer risk disparities. For example, minority and women researchers may better understand and address the needs of their communities through their unique perspective and awareness of issues that are critical to solving disparities in their communities . This unRecognizing the importance of training minority and women scientists in order to more ideally address cancer health disparities, the National Cancer Institute (NCI) and other funders have invested heavily in the development of research and training programs . HoweverThe “UHAND” Program is a collaboration between the University of Houston (UH) and The University of Texas MD Anderson Cancer Center (MDA), funded by the NCI under a Feasibility Studies to Build Collaborative Partnerships in Cancer Research (P20) initiative (PAR-16-084). The purpose of this collaboration is to bring together a minority-serving institution and a comprehensive cancer center to create a comprehensive research/educational training program that would provide opportunities for underrepresented student “scholars” to develop careers in behavioral cancer prevention and cancer disparities research. Although not a requirement of the funding mechanism, both institutions are located close to one another and in Houston, Texas, the 4th largest metropolitan area in the US . The UH The UHAND Program’s overarching goal is to ensure that scholars preparing to join the scientific workforce have the necessary skills and capacity to eliminate cancer inequities through the reduction of social and physical risk factors among disproportionately affected groups. The UHAND Program provides support for developing scholars and early-stage investigators (ESIs) to better understand and conduct intra-institutional research projects that address the social determinants of cancer risk behaviors that predispose Black and Hispanic groups to disproportionate cancer risk. The UHAND Program provides integrated education, broad stakeholder engagement, and targeted approaches to involve women, Hispanic, and Black scholarsin cancer research see . The UHAND Program incorporates best practices of successful training programs, such as the use of a variety of learning methods ,30,31 anThe UHAND Program has four specific goals. The first goal was to develop a research and educational partnership between the UH, MDA, and local community-based organizations to stimulate collaborative cancer disparities research related to tobacco use, poor diet, and physical inactivity among Black and Hispanic individuals. The second goal was to support the development of ESIs through a rigorous Pilot Research Program that facilitates direct-experience proposing, conducting, and leading cancer disparities research, with the support of a larger UHAND Program and its undergraduate, graduate, and postdoctoral scholars. The third goal was to increase the number of underrepresented racial/ethnic minority scholars and faculty engaged in cancer disparities research by providing them with research training, mentorship, and service-learning experiences. Finally, the fourth goal was to develop a robust community outreach program focused on engaging community members in cancer disparities education, research, and clinical trials.There are three main components to the UHAND Program: an Education Program, a Pilot Research Program, and a Community Outreach Program.The Education Program (EP) serves the undergraduate scholars, doctoral scholars (hereafter referred to as graduate scholars), and postdoctoral fellows who represent diverse backgrounds and who were invited to participate in the UHAND Program through a rigorous application and selection process. The EP’s goal is to enable scholars to develop the attitudes, knowledge, and skills necessary to conduct research on reducing cancer disparities, with a focus on lifestyle behaviors  that increase cancer risk for Black and Hispanic adults. This is done by providing the scholars with mentored research projects, seminars in cancer disparities and career development, interactive and community-based service-learning experiences, and summer research experiences, all guided through individual development plans  is comprised of ESIs who work on pilot projects with senior mentors and an experienced investigative team. The PRP provides support to new investigators in developing innovative and impactful research conducted in community and clinical settings within cancer disparities research, particularly within tobacco- and lifestyle-related disparities research. The UHAND Program grant included funding to support two pilot projects: one on the stress-based biological and behavioral cancer risks among Mexican immigrants, and another on a lifestyle intervention for Black prostate cancer patients on active surveillance and their partners. The PRP was later expanded to include additional projects through Administrative Supplements that extended the scope of the initial two pilot projects. The extended scope incorporated the role of physical activity perceptions and barriers in Mexican immigrant cancer risks, and an evaluation of skeletal muscle strength and function among Black prostate cancer survivors in order to reduce the risk of developing cardiometabolic diseases and ultimately, to improve the quality of life in survivorship. UHAND scholars participated in these projects, assisting with data collection and analyses.The Community Outreach Program (COP) is integrated in the cancer health equity development of scholars and in the execution of pilot research projects to increase the real-world impact of these efforts. The COP comprises UHAND team members with community experience and hosts UHAND Programmatic events, informs community members about the UHAND Program, coordinates opportunities for scholars to attend health fairs and seminars, provides scholars with opportunities to present research to community representatives for feedback, works with scholars in fostering presentation skills to community audiences, and offers scholars unique opportunities to connect with the local community. The COP includes a Community Partners Network of local health-based organizations that provide service-learning opportunities for scholars, and Community Mentors who work with scholars on mentor plans and meetings, provide research feedback from the community perspective, enable access to at-risk populations, and identify local opportunities for sharing research findings. The COP team also works closely with the Community Advisory Board . The overall aim of the COP is to enable bi-directional communication between the community and the UHAND scholars to enhance the translation and potential impact of UHAND research.The UHAND Program was funded through two grant awards (P20CA221696 and P20CA221697): one given to a Principal Investigator (PI) at MDA, and another to a PI at UH. Additionally, the components of the UHAND Program  each have co-leadership and support staff from both MDA and UH, facilitating a true partnership between institutions.The UHAND Program is guided by a CAB, an Internal Advisory Committee (IAC), and an External Advisory Board (EAB). The CAB comprises prominent community leaders across a range of sectors in the greater Houston area that work collaboratively with the UHAND team in providing training, outreach, and research activity support, in addition to providing guidance for the dissemination of project findings in the community. The IAC comprises institutional leaders and researchers with equal representation from UH and MDA, and assists with scholar selection, institutional support, and program sustainment. The EAB comprises nationally renowned researchers and provides broad scientific direction to and drives innovation in the UHAND Program’s research activities, in addition to keeping the UHAND team aware of new and innovative research and educational practices in the cancer disparities field.The purpose of this report is to present information on the UHAND Program’s first cohort of scholars and lessons learned that may inform similar training programs. Our objectives, delineated more fully in the Methods section, were broadly to enhance the scholars’ research self-efficacy and academic output through competent mentorship and their sustained participation in the UHAND program, which would ultimately lead to interest in, and be an evidence of, the pursuit of higher education (and/or faculty positions) in the cancer disparities field. Our results are presented in relation to these objectives. This work may provide a comprehensive, evidence- and need-based model for other educational training programs with similar goals for improving cancer health inequities by creating more cancer research career opportunities for women and minorities.The eligibility criteria for admission to the UHAND Program were the following: (1) undergraduate or doctoral student enrolled in, or recently accepted into, a full-time degree program at the UH; (2) having at least 2 years remaining in their degree plans prior to graduation at the start point of the UHAND programming; (3) to have backgrounds in, or be interested in, behavioral and social sciences, social work, communications, biomedical sciences and related public health disciplines, or any other disciplines relevant to studying cancer health disparities; and (4) to be a US Citizen or permanent resident (a requirement of the funder). The eligibility criteria for the postdoctoral fellow included the need to have successfully earned a doctoral degree by the start point of the UHAND programming, and interests in cancer health disparities complementary to those of the intended mentor. In the case of the 1st UHAND Program cohort, that was the UH PI. It was not a requirement to be underrepresented in the sciences to be eligible for UHAND Program participation, but demographic data were collected at the point of application and women and/or individuals from racial/ethnic groups underrepresented in the sciences were prioritized for admission.Undergraduate and graduate scholars were recruited through the UHAND website, UHAND social media accounts, free-standing displays and recruitment materials at UH events, presentations in UH classes, word of mouth from UH faculty members to students, and interactive UH events such as UH Honors College summer research recruiting event and UH career fairs where UHAND team members presented the program . The posUndergraduate and graduate scholars were selected from a variety of UH majors through a 3-level review process. First, the UHAND EP screened application materials and ranked candidates. Next, the UHAND IAC reviewed application materials and ranked applicants. Finally, the UHAND PIs reviewed application materials, received and reviewed rankings, and interviewed candidates. Applications were reviewed for demonstrated academic accomplishments, potential for academic and scholarly success (as indicated from letters of recommendation and transcripts), interest in cancer/health/social disparities, and prior research and/or working experiences. All information was considered by the UHAND PIs in making final admission selections.Out of 5 complete graduate scholar applications and 17 complete undergraduate scholar applications, 3 graduate and 6 undergraduate scholars were invited to join the program. The proportion of undergraduates versus graduate scholars invited to join the first cohort was based on selecting the best candidates of both pools and accounting for the maximum number of scholars we could afford on the budget, balancing that undergraduate inclusion was more affordable than graduate inclusion, based on respective pay rates. As part of their application materials, scholars indicated the top three mentors they would like to work with from a list on UHAND’s website. Potential mentors  were selected by the UHAND PIs based on their engagement in social/behavioral cancer disparities work and their agreement to participate. Scholars were matched to top-choice mentors, with consideration for ensuring distribution across potential mentors. All approached mentors  accepted the scholar as a mentee. Postdoctoral applicants applied to the UH and were interviewed by the UH PI, with whom the selected candidate would directly work. In this case, the successful applicant was not previously associated with either of the partnering institutions.Undergraduate and graduate scholars were paid an hourly rate and committed 20 h per week to work with their research mentors and participate in the UHAND Programming . For undergraduate scholars, UHAND participation also included participation in the UH Summer Undergraduate Research Fellowship (SURF) program, where they learned about various aspects of research—from topics in data science and responsible conduct of research, to learning how to develop effective resumes and poster presentations, applying for awards and graduate school, and managing expectations and challenges in research . They weSurveys with questions on research self-efficacy were administered at baseline (2018), mid-program (2019), and exit (2020). Postdoctoral fellow and graduate scholar responses were combined to facilitate confidentiality. A modified version of Forester et al.’s research self-efficacy scale was used . The oriThe number and category of academic products were assessed by scholar report throughout the duration of the program. Additionally, an annual survey following program exit captured academic products, noting UHAND support that came to fruition following their enrolled period in the UHAND program. Due to the commonly experienced lag between submission and presentation delivery/publication, our timeframe to assess adherence to our explicit goal was extended to the end of the 2020 calendar year . Our explicit goal was to engage UHAND scholars in research, yielding peer-reviewed academic work products such that 2 presentations would be achieved by each undergraduate scholar, 1 presentation and 1 publication would be achieved by each graduate scholar, and 2 presentations and 2 publications would be achieved by the postdoctoral fellow. Goals in excess of this could be pursued by the mentor and mentee as part of the IDP. It is notable that the MDA and the UH PIs were each involved in organizing local conferences to which the scholars could and did submit research for presentation: “Eyes Have Not Seen, Ears Have Not Heard: Breakthroughs in Cancer Research” , and the “Inaugural HEALTH Research Institute conference” (Winter/Spring 2020). Other presentation opportunities included the annual “Undergraduate Research Day” sponsored by the UH Honors College, and a host of national conferences to which scholars could submit abstracts for presentation.Scholar program retention was measured by the comparison of the number of scholars from the time of enrollment to program completion (exit). Our explicit goal was to retain 100% of scholars in the 2-year program by program completion.Surveys with questions on scholar evaluations of their mentors were administered at mid-program and at exit. The postdoctoral fellow and graduate scholar responses were combined to facilitate confidentiality. Fleming et al.’s mentor competency assessment was used . This 26Exit surveys on program feedback and strategies learned were administered to scholars. The postdoctoral fellow and graduate scholar responses were combined to facilitate confidentiality. Scholars were asked to rate their experiences in the following: 10 categories of UHAND educational seminars and sessions on a 5-point Likert scale, from very poor (0) to excellent (4), with an option to select N/A; UHAND programmatic aspects via 12 items on a 5-point Likert scale from very poor (0) to excellent (4); and general program satisfaction in 5 different programmatic activities on a 5-point Likert scale, from very poor (0) to excellent (4), with an option to select N/A. Face valid, investigator-generated items were used to assess confidence in using strategies learned from UHAND trainings, workshops, and books. These questions asked scholars to rate their confidence in time management, conflict resolution, productivity in writing and completing writing projects, engaging in difficult conversations, career exploration, being resilient in academic rejections, and being resilient in discriminatory/unfair experiences in academia/training on a 5-point Likert scale, from not confident at all (0) to completely confident (4), with an option to select N/A. Our explicit goals were to obtain scholar ratings of the UHAND Program and programming, from “good” to “excellent” , and of confidence in using strategies learned in the UHAND Program, from “fairly confident” to “completely confident” .Scholar post-program progression was assessed through surveys that scholars completed monthly during their participation in the program and bi-annually thereafter. Our explicit goal was to have scholars pursue progression in their education and career. Specifically, to have 100% of undergraduate scholars pursue admission to a graduate program , 100% of graduate scholars pursue a postdoctoral training or faculty position, and the postdoctoral fellow obtain a tenure-track faculty position following program completion.Descriptive statistics, including means  and frequencies (and percentages), were calculated for continuous  and binary variables. To account for the small sample size, the Wilcoxon signed-rank test was used to analyze data between matched subjects for differences in distribution and for outcomes of interest over time. Alpha was set at 0.05. All analyses were conducted using SAS 9.4 . p = 0.0273) and from 2018 to 2020 , but not from 2018 to 2019 . Thus, our explicit goal of increasing the research self-efficacy of scholars from baseline (2018) to exit (2020) was achieved. A closer examination by scholar group indicated that the research self-efficacy of undergraduate scholars increased significantly from 2019 to 2020 , but not from 2018 to 2019 , or from 2018 to 2020 . No significant differences were found in graduates/post docs in research self-efficacy scores across years.Five of six undergraduate scholars completed the 2-year program (83.33%), with 1 scholar completing only 1 year due to an opportunity to graduate early. All 3 graduate scholars completed the 2-year program (100%), and the postdoctoral fellow left after a year to take a tenure-track faculty position (0%). Overall, program retention was 80%. As such, we did not achieve our goal to retain 100% of scholars in the 2-year UHAND Program by program completion. However, none of our scholars dropped out of the program while still enrolled in/employed by UH full time; thus, we retained them in the program as long as they remained eligible for support as UHAND scholars .Descriptive statistics for different aspects of the mentee evaluation of mentors by scholars in the 2019 and 2020 surveys are presented in All 6 undergraduate scholars pursued admission into health science graduate (4 scholars) or medical school (2 scholars) programs (100%), 5 of whom have reported program acceptance to date. It is too early to assess the 3 graduate scholars’ program progression, as they are all currently in good standing in graduate school. The postdoctoral fellow secured a tenure-track faculty position. With follow up, we will be able to evaluate the launch of the 3 graduate scholars in their career progression.This report described the implementation of the UHAND Program, a UH and MDA collaboration to create a comprehensive career development training program for scholars underrepresented in the fields of behavioral cancer prevention and cancer disparities research, funded by the NCI’s Partnerships to Advance Cancer Health Equity initiative. The UHAND Program incorporated best practices of successful training programs, such as integrated education  ,30,31; pThe first goal to increase scholars’ research self-efficacy from program baseline to exit was achieved. The UHAND Program provided scholars with research experiences, didactic coursework, career development seminars, and interactive community-based-learning experiences guided through IDPs with their mentors. Scholars were also involved in presenting research to community representatives and audiences, as well as professional/academic audiences. For our undergraduate scholars, they also participated in the SURF program at the UH, which has several didactic research and ethics lectures, tours of labs on campus, and research-building skills over a 10-week summer term. These types of experiences were designed to help build and develop their research self-efficacy skills through mastery via skill-building , vicarious learning , and support . Overall, research self-efficacy significantly increased over the 2-year program, although this was driven by the undergraduate scholars and followed an overall decrease in self-efficacy from the pre-program to the mid-program assessments. The latter may be explained by the Dunning–Kruger Effect, whereby inexperienced people tend to have high confidence and falsely and unknowingly rate their performance highly . Over tiIt is also worthy of note that overall interest in a cancer disparities career declined over time in the program, and the likelihood of pursuing a career in cancer disparities experienced a mid-program dip, similar to scholar self-efficacy. We believe that this pattern may be similarly explained—greater experience with something may reveal nuances and challenges that dissuade further pursuit and alter original intentions based on new information gained through experience. However, it is important to note that these changes were not statistically significant for any group, sample sizes were very small such that a single rater could significantly influence averages, and all average ratings were ≥3.0 in every year and every scholar group, equivalent to “very interested” and “very likely” to pursue a career in health disparities (except for the undergraduates’ mid-program dip to 2.83). Nevertheless, we failed to completely advance interest and intention to extreme interest/likelihood over time for our scholars; this suggests more work is needed to better understand scholars’ responses and thus develop programming to heighten interest/intention, perhaps by further enhancing self-efficacy, addressing imposter syndrome, and/or focusing on scaffolding approaches that clearly indicate pathways to such careers beyond the training program itself. Qualitative feedback, potentially gathered by a researcher not affiliated with the training program, may be helpful in better understanding these patterns and may be an advisable evaluation method to build into similar programs a priori so that issues can be addressed in real-time, as applicable.The second goal was to achieve peer-reviewed academic work products amongst the undergraduate, graduate, and post-doctoral scholars. While all scholars achieved the minimum number of presentations, just over half of the scholars achieved publication goals with wide variability amongst scholars . Variability in achieving publication goals was at least partially attributable to some scholars working on new projects in the design or data collection phase, whereas others worked with existing data that facilitated faster manuscript development. Additionally, the publication of scientific articles often takes time, which may partially explain why some scholars did not achieve the publication goals during the 2-year program. Overall, results inform approaches for program leadership to take when setting expectations with research mentors, who could in turn set specific publication goals with attainable timelines in scholars’ IDPs. This may include recommendations that mentors provide scholars with access to datasets for secondary analysis and manuscript development while they are involved with ongoing research data collection. Other similar programs could make specific recommendations for academic work product outcomes or provide access to datasets for scholars with mentors who do not have secondary data to work with.The third goal—attaining complete 2-year program retention—was not achieved, but not for undesirable reasons. Some scholars obtained outstanding career opportunities for which they left the training program early, such as our postdoctoral scholar, who was offered a tenure-track faculty position. In UHAND, applicants to the program were required to have at least two years remaining prior to graduation so that they could participate in the entire 2-year program; however, training programs need to be flexible for changing circumstances or opportunities over time that may affect a scholar’s original plan. It is noteworthy that apart from the postdoctoral scholar who left the program early due to a job offer, all other scholars remained in the program until completion or (unanticipated early) graduation; this positive result partly supports the high program satisfaction expressed by participants. However, it is important to note that UHAND graduate scholars reported becoming overburdened by UHAND program requirements in their second fellowship year, as they also began their required practicum clinical work in the community, which required additional time and travel that affected their availability for UHAND seminars and trainings. Additionally, two of the three graduate scholars in the UHAND Program were paired with a mentor other than their counseling psychology doctoral mentor, which may have increased the pressure on these scholars to conduct research with UHAND in addition to that with their doctoral program mentor. Thus, the design and duration of future training programs should take into account how scholars’ degree program requirements may vary over time, and how the training program can be adapted in kind to ensure academic success and prevent scholar burn out. Additionally, we recommend that graduate scholars in research training programs similar to UHAND be paired with their doctoral mentors for training program research in order to reduce the burden associated with having multiple research mentors.The fourth goal was to obtain a mentee evaluation of mentors of at least “moderately skilled” in the competencies desired of mentors for the UHAND program, specifically in clear communication, setting expectations, being understanding, fostering independence, respecting diversity, and guiding professional development. We achieved this goal, and thus our program may provide a suitable example for mentor and mentee collaboration. The PIs of the UHAND Program were both department chairs at their respective institutions and had a deep understanding of the faculty across departments doing work in cancer disparities. As the PIs personally knew the mentors and/or supervised them in these roles, they were able to successfully match them with scholars and guide them in this process. Generally, we recommend that other training programs work with individuals who have vast institutional knowledge/experience/connections when selecting mentors for program inclusion. In the absence of such knowledge, or perhaps in any case, programming could also be provided to support and develop the mentors in the execution of their roles. In the UHAND program, we routinely communicated with the mentors about external opportunities  to enhance their mentorship skills, but we offered no formal training ourselves nor did we assess or monitor training that they may have received. In retrospect, offering and assessing the results of mentor training may have further enhanced competencies in this area and might be particularly appropriate for enhancing training with women and minority scholars, who may not be of the same sex/ethnicity/race as their mentors.The fifth and sixth goals were to achieve ratings from “good” to “excellent” on UHAND Program Feedback, and ratings from “fairly” to “completely confident” on strategies learned by our scholars. The programming included a range of seminars designed to enhance time management, facilitate competency in academic writing, explore career options in cancer disparities, and develop skills in presenting oneself and one’s research in both academic and community settings. “Good” to “excellent” scores were achieved for each program element, with the exception of the two tapping into community service-learning experiences. Feedback provided by the scholars indicated that they were, at times, assigned tasks at community agencies that were rather mundane , which contributed to dissatisfaction. Feedback from the community agencies in which scholars were placed indicated that they were used to working with more substantial scholar time commitments than what this portion of the UHAND Program allowed  and thus struggled with how to involve our scholars in substantive and meaningful work. Hence, training programs with service-learning components should explore methods that would enable more time at community agencies, particularly in ways that do not increase overall programmatic time requirements. To give an example, this might be achieved by assisting scholars to get course credit for work with community agencies  or degree-required clinical practice hours in these settings. Despite challenges, program satisfaction was high, and scholars indicated they were “fairly” to “completely confident” in using many of the strategies and skills they were taught in practice .The seventh goal was to track post-program progression, with undergraduate scholars pursuing graduate program admissions, graduate scholars pursuing postdoctoral or faculty positions, and the post-doctoral scholar obtaining a tenure-track faculty position. We achieved this goal with the post-doctoral and undergraduate scholars, the latter of whom went to a combination of master’s degree, doctoral degree, or medical degree programs. It is too early to assess the 3 graduate scholar’s program progressions as they remain in good standing in graduate school. With an ultimate program goal of supporting scholars in pursuit of careers in cancer disparities research, it is important to have programs build processes for continuous monitoring and guidance of scholar achievements that extend beyond graduation and the program funding period. To this end, we will continue to follow our scholars over time to track their academic career achievements and ultimate employment as trained professionals. Mechanisms to bolster continued engagement with scholars over time  will need to be considered.While the UHAND Program achieved many goals, lessons were learned that could enhance similar training programs in the future. Although the UHAND Program represents a model for educational training programs focused on reducing health disparities, particularly those focused on cancer, there are limitations that need to be considered in the evaluation of our goals. These include the fact that lessons may not generalize to other cohorts, institutional collaborations, or mentors. This may especially be the case given the low representation of men (n = 1) in our initial cohort of scholars. Future programs may wish to determine a desired sex distribution a priori and select scholars accordingly, inasmuch as a balance between the sexes is desirable. Additionally, all the graduate scholars were in counseling psychology, which is likely a reflection of the UH PI’s affiliation with that program and the program’s focus on health-oriented, community-engaged work and social justice, which complements the UHAND mission. However, the UHAND Program serves as a model of a grant-supported training program that spanned three diverse educational levels at a minority serving institution, achieved excellent collaboration with a comprehensive cancer center that gave scholars access to many opportunities unavailable at their home institution, and provided diverse scholar access to the cancer center faculty for research training.The UHAND Program may inform other educational training programs that aim to reduce inequities in cancer, and in health more broadly, by increasing the number of underrepresented racial/ethnic minority student scholars through the provision of research training, mentorship, and service-learning opportunities. The UHAND Program also provides an example of successful engagement and collaboration between institutions, and with community via community outreach. On the whole, the UHAND Program may provide a comprehensive, evidence, and need-based model for other educational training programs with similar goals.


In this paper we analyze the performance of QUIC as a transport alternative for Internet of Things (IoT) services based on the Message Queuing Telemetry Protocol (MQTT). QUIC is a novel protocol promoted by Google, and was originally conceived to tackle the limitations of the traditional Transmission Control Protocol (TCP), specifically aiming at the reduction of the latency caused by connection establishment. QUIC use in IoT environments is not widespread, and it is therefore interesting to characterize its performance when in over such scenarios. We used an emulation-based platform, where we integrated QUIC and MQTT (using GO-based implementations) and compared their combined performance with the that exhibited by the traditional TCP/TLS approach. We used Linux containers as end devices, and the ns-3 simulator to emulate different network technologies, such as WiFi, cellular, and satellite, and varying conditions. The results evince that QUIC is indeed an appropriate protocol to guarantee robust, secure, and low latency communications over IoT scenarios. The term Industry 4.0 was originally proposed by the German government in 2011 [One cornerstone of this transformation is the so-called Internet of Things (IoT), which enables the connection of industrial elements that are able to collect and process, in real-time, a large amount of data. This would bring, among other functionalities, the capabilities of monitoring systems, exchanging the gathered (and processed) data, and ascertaining the environment . The devTwo of the most important requirements for IoTare energy efficiency and low latency. Sensor nodes mostly run on batteries, and in many cases, their replacement might be rather complex or even not possible. Hence, it is of paramount importance to ensure long-life sensor operation, yet their costs should be kept reasonable, since it is expected that massive deployments will be needed to cover large or complex systems. On the other hand, if the information gathered by these devices is used for critical decisions (as was mentioned earlier), latency stands out as one of the key performance indicators. The goal is to enable control procedures in  real-time situations.The Message Queuing Telemetry Transport (MQTT) protocol ,4 is oneHence, several solutions have been proposed to tackle the aforementioned limitations. Some of them correspond to TCP modifications and extensions, such as SCTP , Real-TiIn this paper, starting from the proposal of a three-tier fog/cloud architecture that leverages better performance for IoT-based services, we study the performance of the integration of Message Queuing Telemetry Transport (MQTT) with QUIC. We carry out an in-depth analysis, based on a novel methodology, which entails real protocol implementations and Linux containers, and emulation techniques within the ns-3 network simulator. We compare the behavior of this combination with that exhibited by the traditional TCP-based solution.Integration of a fully operational Message Queuing Telemetry Transport (MQTT) implementation with a QUIC GO implementation.All the code that was used to obtain the results presented herewith has been made available in a public git repository.Design and implementation of a methodology to assess the performance of the proposed scheme, using Linux containers and llemulation techniques in ns-3.Performance analysis of MQTT when used on top of QUIC over various network technologies. using an extensive measurement campaign, and an in-depth comparison with a more traditional approach based on TCP.We used peer-to-peer links to emulate different technologies and conditions, and we also assessed the behavior of the proposed schemes considering a scenario where multiple nodes shared the same access.We characterized the gain that can be obtained with some of the features included in the QUIC operation, such as 0-RTT.The main contributions of this paper are:The rest of the paper is structured as follows: QUIC is a transport protocol originally developed by Google Inc. , which hMessage Queuing Telemetry Transport (MQTT)  is a ligMQTT defines three different roles: subscriber, publisher, and broker. Publishers are small sensors, which gather information and publish it into a common register (broker), which keeps information belonging to specific topics. The subscribers access the data provided by the publishers. To do so, they subscribe to a number of topics, and they then receive all messages sent by any publisher on those particular topics.Both publishers and subscribers take the client role in the underlying network topology. On the other hand, the key entity of MQTT is the broker server, which manages the subscriptions and the consequent information delivery to the interested nodes. Hence, all messages published in the network are first sent to the broker, which takes care of forwarding the information to the corresponding subscribers (according to their preliminary registrations). Although clients only interact with a single broker in the current Message Queuing Telemetry Transport (MQTT) specification, the network may contain several brokers, which would actually exchange data among themselves, based on their subscribers’ topics.One of the main advantages of MQTT is that it isolates the operation of data producers (publishers) and consumers (subscribers). This strongly facilitates the implementation of such functionalities in low computational devices, which can interact by exploiting the publish–subscribe scheme. In this sense, since publishers send new content whenever it becomes available, there exists a temporal decoupling between a node’s interest and the publication of such information.QUIC addresses two of the main challenges of today’s web traffic: (1) latency reduction, for a better user experience; and (2) securing the communications , as QUIC established a secure connection in 1 Round Trip Time (RTT) with Transport Layer Security (TLS) protocol version 1.3. This was achieved by combining QUIC and TLS handshakes. TLS 1.3 connection establishment could be further reduced to 0 RTT if the endpoints previously established a communication , a functThe information within a QUIC connection is organized in streams, enabling QUIC to prevent delays caused by head-of-line blocking. When a packet is lost, only streams having data in such packets are blocked while waiting for a retransmission, but other streams can continue . QUIC isIf the packet is not acknowledged and it was sent before an acknowledged packet and one of the following conditions is met:-Either it was sent with an expiring packet time of -Or its packet number is three times smaller than the last acknowledged packet.If the probe timeout is reached, from the moment the packet was sent, and a subsequent packet is not acknowledged.The main difference among TCP loss detection mechanisms is that QUIC does not retransmit lost packets with the same packet numbers. QUIC uses acknowledgment-based detection with a probe timeout to ensure acknowledgments are received. QUIC loss recovery mechanisms are applied in the following scenarios :If the pQUIC encrypts its payload and protects its headers not only to ensure communication security , but alsAlthough the updating process would be easier with QUIC, not all devices could simultaneously change to a newer version, leading to the coexistence of multiple QUIC versions. Correct operation is ensured with a version negotiation mechanism, which allows the endpoints to agree on the version they will use, before the QUIC connection is established. This feature not only simplifies protocol updates, but also allows customizing QUIC with extra features. The endpoints might even share these features as plugins .Even when QUIC was still under development, some researchers had already integrated it in Internet of Things (IoT) protocol stacks ,23. HoweLiri et al. considered QUIC as an IoT protocol, comparing it with IoT specific alternative solutions such as CoAP and MQTT . They prKumar and Dezfouli evaluated Google QUIC’s performance in IoT scenarios . They deLars Eggert studied the feasibility of implementing QUIC in constrained IoT devices . He usedAs the QUIC standardization process has recently concluded with the publication of the corresponding RFC , we foreFinally, it is worth highlighting that this paper amply broadens the analysis discussed in , where wThings. These are the entities that perform measurements to monitor the environment (sensors) or take actions (actuators) to adapt the system’s behavior and its operation. They normally use wireless links to connect with the rest of the architecture.Fog. The traditional cloud approach  has two major limitations. First, it could incur long delays when reaching nodes from the things layer. Secondly, if a fully centralized approach is used, the system might suffer from scalability issues, which might hinder its usefulness. A potential solution would be the distribution of the computational burden among various nodes, bringing them closer to the things. Hence, the use of edge computing, where the servers are next to access elements , is currently receiving interest from the scientific community.Cloud. In IIoT, it might be of great relevance to react as quickly as possible to changes or events. The use of artificial intelligence and machine learning enables the system to make automated decisions, reducing the response time that would be required by traditional human operators. The virtualization and software-defined networks (SDN) paradigms allow the deployment of intelligent agents that leverage this approach in cloud nodes.In our evaluation we consider a three-tier architecture to deploy IIoT services, which includes the following levels :Things. The rapid proliferation of IoT in different areas, particularly in so-called Industry 4.0, is not matched by the pace at which the actual solutions evolve. Message-based protocols, such as MQTT and COAP, which usually rely on traditional client/server architectures, are probably not the most appropriate choice for systems with multiple fog and cloud servers. In particular, some previous papers have analyzed how the three-tier architecture might bring important benefits in terms of operation cost (for distributed storage services), and/or performance, by considering the time required to promote certain decisions ,32.However, the applicability of this architecture might be hindered by the already strong adoption of message-based protocols (MQTT and COAP). In this sense, many of the potential benefits of the proposed three-tier architecture imply the use of rather novel techniques: multi-path communications, coding techniques, and other features. Traditional communications, usually TCP, do not support such functionalities.For instance, multi-path communications can provide interesting benefits to the IIoT realm, since they allow the establishment of different paths to exchange information between the two communication edges, or to naturally send the information to a set of nodes (fog/cloud) that would afterwards cooperate.In IIoT, when things are connected to more than one access element, the use of multi-path could yield better performance and/or reliability, by simultaneously exploiting the various available paths . FurtherWe argue that, in order to promote the aforementioned architecture, the use of TCP might not be an appropriate choice, and we thus propose to use QUIC since it does not only bring latency improvements, as we evaluate herewith, but it also allows easier deployment of its customized versions, thanks to its middlebox independence. One of the most comprehensive studies in extending QUIC with extra features was . In spithttps://github.com/lucas-clemente/quic-go (accessed on 10 April 2020), version 0.15.1.), which follows the IETF QUIC draft version 27. At the time of writing, quic-go implements and facilitates the use of the newly released RFC 9000 [In order to carry out the analysis of QUIC as a transport protocol for IoT, we used a QUIC implementation in GO language, quic-go (RFC 9000 .https://github.com/eclipse/paho.mqtt.golang (accessed on 10 April 2020), version v1.2.0.) and VolantMQ (https://github.com/VolantMQ/volantmq (accessed on 10 April 2020), version v0.4.0-rc6.), respectively. Both of them are implemented in GO and support MQTT 3.1 and 3.1.1. Eclipse Paho builds a library that enables applications to connect to VolantMQ broker using TCP, TLS or WebSocket. Both projects are based on GO 14.0 version, and they are open-source, which allowed us to tweak them to use QUIC, which was also developed with the same GO version. net.go and quic_udp.go.The MQTT client and the server broker are based on open-source Eclipse Paho ).In the client case, all the functionalities at the transport layer, i.e., opening and closing connections, or sending and receiving packets, are managed from the https://github.com/fatimafp95/volantmq_2 (accessed on 10 April 2020)). The transport level functionalities are implemented using transport/conn.go interface. The incompatibilities and restrictions between the connection interfaces offered by TCP and QUIC, this MQTT server only supports QUIC connections. We integrated the quic_udp.go interface, which calls the listener from the server.go interface of quic-go. The listener function is ListenAddrEarly, to enable 0-RTT on the server broker side. This function enables a client that has previously connected to the broker to use the information stored in the cache of that session. Therefore, re-establishing the connection does not require re-negotiating all parameters, so the data exchange happens before the handshakes actually completes.The broker implementation is also open source, and publicly available in a git repository , version 3.24). It provides the possibility to use virtualization techniques to connect traffic from real applications by running LXC Linux containers  over a simulated network. We have deployed an emulated platform, based on the scenario depicted in Experiments were performed using the discrete-event network simulator for internet systems ns-3 . These routers are connected over two links, which emulate different technologies. These are configured using the parameters depicted on In a second scenario, we changed the connection between the publisher and the broker, and we used WiFi to connect Linux containers. This feature allowed us to analyze the performance of the combination of MQTT and QUIC over a shared channel. In this case, the connection between broker and subscriber emulates an end-to-end connection over a high bandwidth network. In order to facilitate the execution of systematic and repetitive experiments, mimicking the conditions that were used for the previous scenario, we have modified the error model originally implemented in ns-3, allowing us to precisely control the frame error rate, regardless of the interference model. Furthermore, we have run experiments modifying the maximum number of retransmissions, which are defined in IEEE 802.11 MAC protocol  to assesWe define Scenario B based on an ad-hoc wireless network that connects various Linux containers, acting as MQTT publishers, to the broker server over a shared WiFi network. As mentioned earlier, the broker and the subscriber are connected over a P2P link, whose characteristics are fixed to emulate a high bandwidth end-to-end network. In this section, we discuss the performance of MQTT over QUIC, comparing it with the performance exhibited by a more traditional approach which uses TCP and TLS. We discuss results obtained during an intensive experiment campaign carried out over the scenarios that were described in In order to fairly compare the performance of QUIC and TCP, we use their absolute completion times, according to the two parameters defined in fer to ∆ a. This rith packet was only sent after ensuring the subscriber got the previous one. We measured the time required to correctly receive the 100 messages  and the cloud is the large distance between the latter two, which directly hinders the latency. The performance improvement achieved with QUIC is not expected to change significantly if the conditions of the fog/edge to cloud connection change. We verified this by repeating the completion time evaluation but changing the characteristics of the link connecting the broker, which is representing fog layer, and the subscriber, the cloud. In this experiment, the p2p link emulated a 10 Gbps connection with RTT values of 1, and 100 milliseconds (ms), to reflect a broad range of conditions. The results are depicted in The following results are based on Scenario B, in which we used both traffic patterns. We considered several MQTT clients connected to the broker over a shared WiFi network. This setup mimicked a wireless sensor network in a three-tier (fog/cloud) architecture  over a shared WiFi network to a broker (fog), which consequently relayed the information to a subscriber (cloud), over a P2P network that mimicked the connectivity between fog and the cloud. Thanks to the simulator and its ability to connect Linux containers, we thoroughly assessed the performance of using QUIC as a transport protocol for MQTT traffic, and we compared it with the traditional MQTT/TLS/TCP stack.Despite the implementations’ restrictions, we developed two complementary scenarios to analyze the behavior of MQTT with both QUIC and TCP. Since the envisaged services have stringent requirements in terms of latency, our evaluation focused on the delay. In this sense, we saw that QUIC clearly outperforms TCP, especially for connections with low RTT and high packet erasure rates. On the other hand, we have also ascertained the benefits of the 0-RTT scheme that QUIC promotes. The results show a clear reduction of latency upon connection establishment. QUIC also yields a more predictable behavior, with much less variability in the results. Finally, we have evaluated QUIC on shared channels, by having multiple things (Linux containers) sending publish messages to the broker over a shared WiFi network. The results evince that QUIC yields a good behavior over shared environments.All the code that was used to carry out the experiments described in the paper has been made available as public git repositories.In our future work, we will exploit the methodology we have proposed in this paper to further broaden the evaluation of QUIC as a transport protocol for IIoT environments. We will integrate some of the additional features that are, at the time of writing, under development, such as multi-path. Another QUIC characteristic that was not integrated in the implementation we used is piggybacking, and this might yield some performance improvements, so it might be of interest to assess its behavior. We will also study the impacts of having different traffic patterns and various congestion control algorithms. The platform that was developed in this work would facilitate the evaluation of all these features.