• A model for rigorously applying the Exploration, Preparation, Implementation, Sustainment (EPIS) framework in the design and measurement of a large scale collaborative multi-site study

      Becan, JE; Bartkowski, JP; Knight, DK; Wiley, TRA; DiClemente, R; Ducharme, L; Welsh, WN; Bowser, D; McCollister, K; Hiller, M; Spaulding, AC; Flynn, PM; Swartzendruber, A; Dickson, MF; Fisher, JH; Aarons, GA (2018-12-01)
      © 2018, The Author(s). Background: This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners. Methods: The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline. Discussion: The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations. Trial registration: NCT02672150. Retrospectively registered on 22 January 2016.
    • A molecular determinant of phosphoinositide affinity in mammalian TRPV channels

      Velisetty, P; Borbiro, I; Kasimova, MA; Liu, L; Badheka, D; Carnevale, V; Rohacs, T; Carnevale, Vincenzo|0000-0002-0447-1278 (2016-06-13)
      Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ] is an important cofactor for ion channels. Affinity for this lipid is a major determinant of channel inhibition by depletion of PI(4,5)P2 upon phospholipase C (PLC) activation. Little is known about what determines PI(4,5)P2 affinity in mammalian ion channels. Here we report that two members of the Transient Receptor Potential Vanilloid (TRPV) ion channel family, TRPV5 and TRPV6 lack a positively charged residue in the TM4-TM5 loop that was shown to interact with PI(4,5)P2 in TRPV1, which shows high affinity for this lipid. When this positively charged residue was introduced to either TRPV6 or TRPV5, they displayed markedly higher affinities for PI(4,5)P2, and were largely resistant to inhibition by PI(4,5)P2 depletion. Furthermore, Ca2+ -induced inactivation of TRPV6 was essentially eliminated in the G488R mutant, showing the importance of PLC-mediated PI(4,5)P2 depletion in this process. Computational modeling shows that the introduced positive charge interacts with PI(4,5)P2 in TRPV6.
    • A molecular timescale of eukaryote evolution and the rise of complex multicellular life

      Hedges, SB; Blair, JE; Venturi, ML; Shoe, JL (2004-01-28)
      Background: The pattern and timing of the rise in complex multicellular life during Earth's history has not been established. Great disparity persists between the pattern suggested by the fossil record and that estimated by molecular clocks, especially for plants, animals, fungi, and the deepest branches of the eukaryote tree. Here, we used all available protein sequence data and molecular clock methods to place constraints on the increase in complexity through time. Results: Our phylogenetic analyses revealed that (i) animals are more closely related to fungi than to plants, (ii) red algae are closer to plants than to animals or fungi, (iii) choanoflagellates are closer to animals than to fungi or plants, (iv) diplomonads, euglenozoans, and alveolates each are basal to plants+animals+fungi, and (v) diplomonads are basal to other eukaryotes (including alveolates and euglenozoans). Divergence times were estimated from global and local clock methods using 20-188 proteins per node, with data treated separately (multigene) and concatenated (supergene). Different time estimation methods yielded similar results (within 5%): vertebrate-arthropod (964 million years ago, Ma), Cnidaria-Bilateria (1,298 Ma), Porifera-Eumetozoa (1,351 Ma), Pyrenomycetes-Plectomycetes (551 Ma), Candida-Saccharomyces (723 Ma), Hemiascomycetes-filamentous Ascomycota (982 Ma), Basidiomycota-Ascomycota (968 Ma), Mucorales-Basidiomycota (947 Ma), Fungi-Animalia (1,513 Ma), mosses-vascular plants (707 Ma), Chlorophyta- Tracheophyta (968 Ma), Rhodophyta-Chlorophyta+Embryophyta (1,428 Ma), Plantae-Animalia (1,609 Ma), Alveolata-plants+animals+fungi (1,973 Ma), Euglenozoa-plants+animals+fungi (1,961 Ma), and Giardia-plants+animals+fungi (2,309 Ma). By extrapolation, mitochondria arose approximately 2300-1800 Ma and plastids arose 1600-1500 Ma. Estimates of the maximum number of cell types of common ancestors, combined with divergence times, showed an increase from two cell types at 2500 Ma to ∼10 types at 1500 Ma and 50 cell types at ∼1000 Ma. Conclusions: The results suggest that oxygen levels in the environment, and the ability of eukaryotes to extract energy from oxygen, as well as produce oxygen, were key factors in the rise of complex multicellular life. Mitochondria and organisms with more than 2-3 cell types appeared soon after the initial increase in oxygen levels at 2300 Ma. The addition of plastids at 1500 Ma, allowing eukaryotes to produce oxygen, preceded the major rise in complexity. © 2004 Hedges et al; licensee BioMed Central Ltd.
    • A multicenter REtrospective observational study of first-line treatment with PERtuzumab, trastuzumab and taxanes for advanced HER2 positive breast cancer patients. RePer Study

      Gamucci, T; Pizzuti, L; Natoli, C; Mentuccia, L; Sperduti, I; Barba, M; Sergi, D; Iezzi, L; Maugeri-Saccà, M; Vaccaro, A; Magnolfi, E; Gelibter, A; Barchiesi, G; Magri, V; D’Onofrio, L; Cassano, A; Rossi, E; Botticelli, A; Moscetti, L; Omarini, C; Fabbri, MA; Scinto, AF; Corsi, D; Carbognin, L; Mazzotta, M; Bria, E; Foglietta, J; Samaritani, R; Garufi, C; Mariani, L; Barni, S; Mirabelli, R; Sarmiento, R; Graziano, V; Santini, D; Marchetti, P; Tonini, G; Di Lauro, L; Sanguineti, G; Paoletti, G; Tomao, S; De Maria, R; Veltri, E; Paris, I; Giotta, F; Latorre, A; Giordano, A; Ciliberto, G; Vici, P; Giordano, Antonio|0000-0002-5959-016X (2019-02-01)
      © 2018, © 2018 The Author(s). Published by Taylor & Francis. We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance were 21, 4 and 15 months, respectively. The response rate was 77.3%, and the clinical benefit rate 93.6%. Median progression-free survival (mPFS) was 21 months, and median overall survival (mOS) was not reached. When comparing patients by trastuzumab-pretreatment, similar PFS were observed, although a longer OS was reached in trastuzumab-naïve patients (p = 0.02). Brain metastases at baseline and their development in course of therapy were associated with significantly shorter PFS (p = 0.0006) and shorter OS, although at a not fully statistically relevant extent (p = 0.06). The addition of maintenance endocrine therapy (ET) to pertuzumab/trastuzumab maintenance was associated with longer PFS (p = 0.0001), although no significant differences were detected in OS (p = 0.31). Results were confirmed by propensity score analysis (p = 0.003 and p = 0.46, respectively). In multivariate models, longer PFS was related to lower Performance Status (PS) (p = 0.07), metastatic stage at diagnosis (p = 0.006) and single metastatic site (p < 0.0001). An OS advantage was observed with lower PS (p < 0.0001), single metastatic site (p = 0.004), no prior exposure to trastuzumab (p = 0.004) and response to pertuzumab-based treatment (p = 0.003). Our results confirm that trastuzumab/pertuzumab/taxane is the standard of care as first-line treatment of patients with HER2-positive ABC even in the real-world setting. Moreover, the double-maintenance therapy (HER2 block and ET) is strongly recommended when feasible.
    • A National Study on the Effects of Concussion in Collegiate Athletes and US Military Service Academy Members: The NCAA–DoD Concussion Assessment, Research and Education (CARE) Consortium Structure and Methods

      Broglio, SP; McCrea, M; McAllister, T; Harezlak, J; Katz, B; Hack, D; Hainline, B; Hoy, A; Hazzard, JB; Kelly, LA; Ortega, JD; Port, N; Putukian, M; Langford, TD; Tierney, R; Campbell, DE; McGinty, G; O’Donnell, P; Benjamin, HJ; Buckley, T; Kaminski, TW; Clugston, JR; Schmidt, JD; Feigenbaum, LA; Eckner, JT; Guskiewicz, K; Mihalik, JP; Miles, JD; Master, CL; Collins, M; Kontos, AP; Bazarian, JJ; Chrisman, SPD; Bullers, CT; Miles, CM; Dykhuizen, BH (2017-07-01)
      © 2017, The Author(s). Background: The natural history of mild traumatic brain injury (TBI) or concussion remains poorly defined and no objective biomarker of physiological recovery exists for clinical use. The National Collegiate Athletic Association (NCAA) and the US Department of Defense (DoD) established the Concussion Assessment, Research and Education (CARE) Consortium to study the natural history of clinical and neurobiological recovery after concussion in the service of improved injury prevention, safety and medical care for student-athletes and military personnel. Objectives: The objectives of this paper were to (i) describe the background and driving rationale for the CARE Consortium; (ii) outline the infrastructure of the Consortium policies, procedures, and governance; (iii) describe the longitudinal 6-month clinical and neurobiological study methodology; and (iv) characterize special considerations in the design and implementation of a multicenter trial. Methods: Beginning Fall 2014, CARE Consortium institutions have recruited and enrolled 23,533 student-athletes and military service academy students (approximately 90% of eligible student-athletes and cadets; 64.6% male, 35.4% female). A total of 1174 concussions have been diagnosed in participating subjects, with both concussion and baseline cases deposited in the Federal Interagency Traumatic Brain Injury Research (FITBIR) database. Conclusions: Challenges have included coordinating regulatory issues across civilian and military institutions, operationalizing study procedures, neuroimaging protocol harmonization across sites and platforms, construction and maintenance of a relational database, and data quality and integrity monitoring. The NCAA–DoD CARE Consortium represents a comprehensive investigation of concussion in student-athletes and military service academy students. The richly characterized study sample and multidimensional approach provide an opportunity to advance the field of concussion science, not only among student athletes but in all populations at risk for mild TBI.
    • A new method for inferring timetrees from temporally sampled molecular sequences

      Miura, S; Tamura, K; Tao, Q; Huuki, LA; Kosakovsky Pond, SL; Priest, J; Deng, J; Kumar, S; Kumar, Sudhir|0000-0002-9918-8212 (2020-01-01)
      © 2020 Miura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Pathogen timetrees are phylogenies scaled to time. They reveal the temporal history of a pathogen spread through the populations as captured in the evolutionary history of strains. These timetrees are inferred by using molecular sequences of pathogenic strains sampled at different times. That is, temporally sampled sequences enable the inference of sequence divergence times. Here, we present a new approach (RelTime with Dated Tips [RTDT]) to estimating pathogen timetrees based on a relative rate framework underlying the RelTime approach that is algebraic in nature and distinct from all other current methods. RTDT does not require many of the priors demanded by Bayesian approaches, and it has light computing requirements. In analyses of an extensive collection of computer-simulated datasets, we found the accuracy of RTDT time estimates and the coverage probabilities of their confidence intervals (CIs) to be excellent. In analyses of empirical datasets, RTDT produced dates that were similar to those reported in the literature. In comparative benchmarking with Bayesian and non-Bayesian methods (LSD, TreeTime, and treedater), we found that no method performed the best in every scenario. So, we provide a brief guideline for users to select the most appropriate method in empirical data analysis. RTDT is implemented for use via a graphical user interface and in high-throughput settings in the newest release of cross-platform MEGA X software, freely available from http://www.megasoftware.net.
    • A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure

      Komiya, Y; Bai, Z; Cai, N; Lou, L; Al-Saadi, N; Mezzacappa, C; Habas, R; Runnels, LW (2017-12-01)
      © 2017 The Author(s). In humans, germline mutations in Trpm6 cause autosomal dominant hypomagnesemia with secondary hypocalcemia disorder. Loss of Trpm6 in mice also perturbs cellular magnesium homeostasis but additionally results in early embryonic lethality and neural tube closure defects. To define the mechanisms by which TRPM6 influences neural tube closure, we functionally characterized the role of TRPM6 during early embryogenesis in Xenopus laevis. The expression of Xenopus TRPM6 (XTRPM6) is elevated at the onset of gastrulation and is concentrated in the lateral mesoderm and ectoderm at the neurula stage. Loss of XTRPM6 produced gastrulation and neural tube closure defects. Unlike XTRPM6′s close homologue XTRPM7, whose loss interferes with mediolateral intercalation, depletion of XTRPM6 but not XTRPM7 disrupted radial intercalation cell movements. A zinc-influx assay demonstrated that TRPM6 has the potential to constitute functional channels in the absence of TRPM7. The results of our study indicate that XTRPM6 regulates radial intercalation with little or no contribution from XTRPM7 in the region lateral to the neural plate, whereas XTRPM7 is mainly involved in regulating mediolateral intercalation in the medial region of the neural plate. We conclude that both TRPM6 and TRPM7 channels function cooperatively but have distinct and essential roles during neural tube closure.
    • A novel dual signaling axis for NSP 5a3a induced apoptosis in head and neck carcinoma

      D'Agostino, L; Giordano, A; Giordano, Antonio|0000-0002-5959-016X (2011-01-01)
      NSP 5a3a is a novel structural protein found to be over-expressed in certain cancer cell lines in-vitro such as Hela, Saos-2, and MCF-7 while barely detectable levels in normal body tissues except for Testis. This particular isoform has been known to interact with cyto- nuclear proteins B23, known to be involved in multi-faceted cellular processes such as cell division, apoptosis, ribosome biogenesis, and rRNA processing, as well as with hnRNP-L, known to be involved with RNA metabolism and rRNA processing. A previous preliminary investigation of NSP 5a3a as a potential target in Head and Neck Carcinoma revealed a novel p73 dependent mechanism through which NSP 5a3a induced apoptosis in Head and Neck cell lines when overexpressed in-vitro. Our present investigation further elucidated a novel dual axis signaling point by which NSP 5a3a induces apoptosis in Head and Neck cell line HN30 through p73-DAXX and TRAF2-TRADD. Interestingly, this novel mechanism appears independent of canonical caspases involved in the intrinsic mitochondrial pathway as well as those in the death receptor pathway thru TRAF2 and TRADD. © D'Agostino et al.
    • A novel dynamic neonatal blood-brain barrier on a chip

      Deosarkar, SP; Prabhakarpandian, B; Wang, B; Sheffield, JB; Krynska, B; Kiani, MF; Kiani, Mohammad|0000-0003-1533-0179 (2015-11-10)
      © 2015 Deosarkar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Studies of neonatal neural pathologies and development of appropriate therapeutics are hampered by a lack of relevant in vitro models of neonatal blood-brain barrier (BBB). To establish such a model, we have developed a novel blood-brain barrier on a chip (B3C) that comprises a tissue compartment and vascular channels placed side-by-side mimicking the three-dimensional morphology, size and flow characteristics of microvessels in vivo. Rat brain endothelial cells (RBEC) isolated from neonatal rats were seeded in the vascular channels of B3C and maintained under shear flow conditions, while neonatal rat astrocytes were cultured under static conditions in the tissue compartment of the B3C. RBEC formed continuous endothelial lining with a central lumen along the length of the vascular channels of B3C and exhibited tight junction formation, as measured by the expression of zonula occludens-1 (ZO-1). ZO-1 expression significantly increased with shear flow in the vascular channels and with the presence of astrocyte conditioned medium (ACM) or astrocytes cultured in the tissue compartment. Consistent with in vivo BBB, B3C allowed endfeet-like astrocyte-endothelial cell interactions through a porous interface that separates the tissue compartment containing cultured astrocytes from the cultured RBEC in the vascular channels. The permeability of fluorescent 40 kDa dextran from vascular channel to the tissue compartment significantly decreased when RBEC were cultured in the presence of astrocytes or ACM (from 41.0±0.9 x 10?6 cm/s to 2.9±1.0 x 10?6 cm/s or 1.1±0.4 x 10?6 cm/s, respectively). Measurement of electrical resistance in B3C further supports that the addition of ACM significantly improves the barrier function in neonatal RBEC. Moreover, B3C exhibits significantly improved barrier characteristics compared to the transwell model and B3C permeability was not significantly different from the in vivo BBB permeability in neonatal rats. In summary, we developed a first dynamic in vitro neonatal BBB on a chip (B3C) that closely mimics the in vivo microenvironment, offers the flexibility of real time analysis, and is suitable for studies of BBB function as well as screening of novel therapeutics.
    • A patient-oriented clinical decision support system for CRC risk assessment and preventative care

      Liu, J; Li, C; Xu, J; Wu, H; Wu, Huanmei|0000-0003-0346-6044 (2018-12-07)
      © 2018 The Author(s). Background: Colorectal Cancer (CRC) is the third leading cause of cancer death among men and women in the United States. Research has shown that the risk of CRC associates with genetic and lifestyle factors. It is possible to prevent or minimize certain CRC risks by adopting a healthy lifestyle. Existing Clinical Decision Support Systems (CDSS) mainly targeted physicians as the CDSS users. As a result, the availability of patient-oriented CDSS is limited. Our project is to develop patient-oriented CDSS for active CRC management. Methods: We implemented an online patient-oriented CRC CDSS for the public to learn about CRC, assess CRC risk levels, understand personalized CRC risk factors, and seek professional advices for people with CRC concerns. The system is implemented based on the Django Model-View-Controller (MVC) framework with an extensible background MySQL database. A CRC absolute risk prediction model is applied to calculate the personalized CRC risk score with a user-friendly web survey. An interactive dashboard using advanced data visualization technics will display and interpret the risk scores and factors. Based on the risk assessment, a structured decision tree algorithm will provide the recommendations on customized CRC screening methods. The CDSS also provides a search function for preferred providers and hospitals based on geographical information and patient preferences. Results: A prototype of the patient-oriented CRC CDSS has been developed. It provides an open assessment of potential CRC risks via an online survey. The CRC risk predictive model has been implemented. The prediction outcomes of risk levels and factors are presented to the users through a personalized interactive visualization interface, to guide the public on how to reduce the CRC risks by changing their living styles (such as smoking and drinking) and diet characteristics (such as consumptions of red meat and milk). The CDSS will also provide customized recommendations on screening methods based on the corresponding risk factors. For users seeking professional clinicians, the CDSS also provides a convenient tool for searching nearby hospitals and available doctors based on the location preferences and providers characteristics (such as gender, language, and specialty). Conclusions: This CRC CDSS prototype provides a patient-friendly interface for CRC risk assessment and gives a personalized interpretation on important CRC risk factors. It is a useful tool to educate the public on CRC, to provide guidance on minimizing CRC risks, and to promote early CRC screening that reduces the CRC occurrences.
    • A performance analysis model of TCP over multiple heterogeneous paths for 5G mobile services

      Song, J; Dong, P; Zhou, H; Zheng, T; Du, X; Guizani, M; Du, Xiaojiang|0000-0003-4235-9671 (2018-05-01)
      © 2018 by the authors. Driven by the primary requirement of emerging 5G mobile services, the demand for concurrent multipath transfer (CMT) is still prominent. Yet, multipath transport protocols are not widely adopted and CMT schemes based on Transport Control Protocol (TCP) will still be in dominant position in 5G. However, the performance of TCP flow transferred over multiple heterogeneous paths is prone to the link quality asymmetry, the extent of which was revealed to be significant by our field investigation. In this paper, we present a performance analysis model for TCP over multiple heterogeneous paths in 5G scenarios, where both bandwidth and delay asymmetry are taken into consideration. The evaluation using large-scale simulation and field experiment shows that the proposed model can achieve high accuracy in practical environments. Some interesting inferences can be drawn from the proposed model, such as the dominant factors that affect the performance of TCP over heterogeneous networks, and the criteria of determining the appropriate number of links to be used under different circumstances of path heterogeneity. Thus, the proposed model can provide a guidance to the design of TCP-based CMT solutions for 5G mobile services.
    • A phase III randomized three-arm trial of physical therapist delivered pain coping skills training for patients with total knee arthroplasty: The KASTPain protocol

      Riddle, DL; Keefe, FJ; Ang, D; J, K; Dumenci, L; Jensen, MP; Bair, MJ; Reed, SD; Kroenke, K (2012-08-27)
      Abstract. Background: Approximately 20% of patients report persistent and disabling pain following total knee arthroplasty (TKA) despite an apparently normally functioning prosthesis. One potential risk factor for unexplained persistent pain is high levels of pain catastrophizing. We designed a three-arm trial to determine if a pain coping skills training program, delivered prior to TKA, effectively reduces function-limiting pain following the procedure in patients with high levels of pain catastrophizing. Methods/design. The trial will be conducted at four University-based sites in the US. A sample of 402 patients with high levels of pain catastrophizing will be randomly assigned to either a pain coping skills training arm, an arthritis education control arm or usual care. Pain coping skills will be delivered by physical therapists trained and supervised by clinical psychologist experts. Arthritis education will be delivered by nurses trained in the delivery of arthritis-related content. The primary outcome will be change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale score 12 months following surgery. A variety of secondary clinical and economic outcomes also will be evaluated. Discussion. The trial will be conducted at four University-based sites in the US. A sample of 402 patients with high levels of pain catastrophizing will be randomly assigned to either a pain coping skills training arm, an arthritis education control arm or usual care. Pain coping skills will be delivered by physical therapists trained and supervised by clinical psychologist experts. Arthritis education will be delivered by nurses trained in the delivery of arthritis-related content. The primary outcome will be change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale score 12 months following surgery. A variety of secondary clinical and economic outcomes also will be evaluated. Trial Registration. NCT01620983. © 2012 Riddle et al.; licensee BioMed Central Ltd.
    • A Pilot Randomized Controlled Trial of a Technology-Based Approach for Preventing Excess Weight Gain during Pregnancy among Women with Overweight

      Chao, AM; Srinivas, SK; Studt, SK; Diewald, LK; Sarwer, DB; Allison, KC; Sarwer, David B|0000-0003-1033-5528 (2017-11-22)
      © Copyright © 2017 Chao, Srinivas, Studt, Diewald, Sarwer and Allison. Objective: Overweight/obesity and excess weight gain during pregnancy are associated with adverse maternal and neonatal outcomes. Few interventions have been effective in limiting gestational weight gain among women with overweight or obesity. This pilot, randomized clinical trial compared treatment as usual (TAU) to a lifestyle modification program delivered via phone for the prevention of excess gestational weight gain in women who had overweight or obesity. Methods: Participants included 41 pregnant women with a body mass index (BMI) ≥ 25 kg/m2 (mean age = 28.7 ± 5.8 years; mean pre-gravid BMI = 31.2 ± 6.2 kg/m2; 54% black, 39% white). The intervention group (n = 20) received weekly telephone counseling sessions and used WiFi scales to monitor their weight from weeks 16 to 36 of pregnancy. We compared differences in weight and birth outcomes for the intervention vs. the TAU group (n = 21). Results: The intervention and TAU groups did not differ with respect to: gestational weight gain (15.5 ± 5.3 vs. 13.3 ± 6.8 kg, respectively); proportion gaining above the 2009 Institute of Medicine recommended weight range (83 vs. 70%); and weight gain from pre-pregnancy weight to 6 weeks postpartum (4.8 ± 4.6 vs. 3.0 ± 5.5 kg). Other birth and health outcomes also did not differ. Conclusion: A telemedicine intervention designed to decrease logistical burden on participants was not more successful in reducing excessive weight gain during pregnancy as compared to TAU. Future studies should examine more intensive forms of remote treatment beginning earlier in pregnancy as well as interventions promoting a healthy weight prior to pregnancy.
    • A pilot randomized controlled trial testing the effects of a routine‐based intervention on outcomes in a behavioural weight loss programme

      Demos, KE; Leahey, TM; Hart, CN; Trautvetter, J; Coward, PR; Duszlak, J; Wing, RR (2015-12)
      BACKGROUND: Structured routines aimed at eating and sleep have been successfully employed in weight loss interventions for children. Although such routines are discussed in lifestyle modification programmes for adults, they are not a primary focus. PURPOSE: The purpose of this study is to determine if establishing healthy eating and sleep routines may improve outcomes in a behavioural weight loss (BWL) intervention. METHODS: Twenty-five overweight/obese participants (age = 52.4 ± 9.8; body mass index = 33.5 ± 4.1) were randomly assigned to either a 4-week routine-based intervention (ROU) targeting regular eating and sleep or an education control before beginning an 18-week BWL intervention. RESULTS: Routine-based intervention participants reported adhering to eating routines, with increased 'on-schedule' eating (p = 0.007) and decreased 'off-schedule' eating (p = 0.002) but showed no change in 'on-schedule' sleep (p = 0.74). However, contrary to our hypothesis, ROU participants lost less weight than controls after 6 weeks of BWL (2.3 ± 2.5 vs. 4.6 ± 2.6 kg, p = 0.04) and achieved only modest weight loss over the full 18 weeks (ROU: 3.2 ± 4.6 vs. education control: 5.8 ± 5.7 kg, p = 0.23). CONCLUSIONS: Focusing initially on establishing healthy sleep and eating routines led to poorer, rather than better, subsequent weight loss outcomes. Further studies using a longer initial intervention period or focusing on only sleep or eating behaviour are needed to determine whether establishing routines for eating and sleep behaviours can enhance weight loss in adults.
    • A pilot study on the impact of known drug-drug interactions in cancer patients

      Ussai, S; Petelin, R; Giordano, A; Malinconico, M; Cirillo, D; Pentimalli, F; Giordano, Antonio|0000-0002-5959-016X (2015-08-25)
      © 2015 Ussai et al. Background: When a patient concomitantly uses two or more drugs, a drug-drug interaction (DDI) can possibly occur, potentially leading to an increased or decreased clinical effect of a given treatment. Cancer patients are at high risk of such interactions because they commonly receive multiple medications. Moreover, most cancer patients are elderly and require additional medications for comorbidities. Aim of this preliminary observational study was to evaluate the incidence of well known and established DDIs in a cohort of cancer outpatients undergoing multiple treatments. Methods: Anamnestic and clinical data were collected for 64 adult patients in the ambulatory setting with malignant solid tumors who were receiving systemic anticancer treatment. Patients also declared all drugs prescribed by other specialists or self-taken in the previous 2 weeks. DDIs were divided into two different groups: 'neoplastic DDIs' (NDDIs), involving antitumoral drugs, and 'not neoplastic DDIs' (nDDIs), involving all other classes of drugs. The severity of DDIs was classified as major, moderate and minor, according to the 'Institute for Pharmacological Research Mario Negri' definition. Results: About 34 % of cancer outpatients within our cohort were prescribed/assumed interacting drug combinations. The most frequent major NDDIs involved the anticoagulant warfarin (33 % of total NDDIs) that, in association with tamoxifen, or capecitabine and paclitaxel, increased the risk of haemorrhage. About 60 % of nDDIs involved acetylsalicylic acid. Conclusions: Overall, 16 % of DDIs were related to an A-level strength of recommendation to be avoided. The lack of effective communication among specialists and patients might have a role in determining therapeutic errors. Our pilot study, although limited by a small cohort size, highlights the urgent need of implementing the clinical management of cancer outpatients with new strategies to prevent or minimize potential harmful DDIs.
    • A population genetic assessment of taxonomic species: The case of Lake Malawi cichlid fishes

      Pinho, C; Cardoso, V; Hey, J (2019-09-01)
      © 2019 The Authors. Molecular Ecology Resources Published by John Wiley & Sons Ltd. Organisms sampled for population-level research are typically assigned to species by morphological criteria. However, if those criteria are limited to one sex or life stage, or the organisms come from a complex of closely related forms, the species assignments may misdirect analyses. The impact of such sampling can be assessed from the correspondence of genetic clusters, identified only from patterns of genetic variation, to the species identified using only phenotypic criteria. We undertook this protocol with the rock-dwelling mbuna cichlids of Lake Malawi, for which species within genera are usually identified using adult male coloration patterns. Given high local endemism of male colour patterns, and considerable allele sharing among species, there persists considerable taxonomic uncertainty in these fishes. Over 700 individuals from a single transect were photographed, genotyped and separately assigned: (a) to morphospecies using photographs; and (b) to genetic clusters using five widely used methods. Overall, the correspondence between clustering methods was strong for larger clusters, but methods varied widely in estimated number of clusters. The correspondence between morphospecies and genetic clusters was also strong for larger clusters, as well as some smaller clusters for some methods. These analyses generally affirm (a) adult male-limited sampling and (b) the taxonomic status of Lake Malawi mbuna, as the species in our study largely appear to be well-demarcated genetic entities. More generally, our analyses highlight the challenges for clustering methods when the number of populations is unknown, especially in cases of highly uneven sample sizes.
    • A pragmatic application of the RE-AIM framework for evaluating the implementation of physical activity as a standard of care in health systems

      Stoutenberg, M; Galaviz, KI; Lobelo, F; Joy, E; Heath, GW; Hutber, A; Estabrooks, P; Stoutenberg, Mark|0000-0001-5206-7627 (2018-05-01)
      © 2018 Centers for Disease Control and Prevention (CDC). Introduction Exercise is Medicine (EIM) is an initiative that seeks to integrate physical activity assessment, prescription, and patient referral as a standard in patient care. Methods to assess this integration have lagged behind its implementation. Purpose and Objectives The purpose of this work is to provide a pragmatic framework to guide health care systems in assessing the implementation and impact of EIM. Evaluation Methods A working group of experts from health care, public health, and implementation science convened to develop an evaluation model based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. The working group aimed to provide pragmatic guidance on operationalizing EIM across the different RE-AIM dimensions based on data typically available in health care settings. Results The Reach of EIM can be determined by the number and proportion of patients that were screened for physical inactivity, received brief counseling and/or a physical activity prescription, and were referred to physical activity resources. Effectiveness can be assessed through self-reported changes in physical activity, cardiometabolic biometric factors, incidence/burden of chronic disease, as well as health care utilization and costs. Adoption includes assessing the number and representativeness of health care settings that adopt any component of EIM, and Implementation involves assessing the extent to which health care teams implement EIM in their clinic. Finally, Maintenance involves assessing the long-term effectiveness (patient level) and sustained implementation (clinic level) of EIM in a given health care setting. Implications for Public Health The availability of a standardized, pragmatic, evaluation framework is critical in determining the impact of implementing EIM as a standard of care across health care systems.
    • A privacy-preserving traffic monitoring scheme via vehicular crowdsourcing

      Zhang, C; Zhu, L; Xu, C; Du, X; Guizani, M; Du, Xiaojiang|0000-0003-4235-9671 (2019-03-02)
      © 2019 by the authors. Licensee MDPI, Basel, Switzerland. The explosive number of vehicles has given rise to a series of traffic problems, such as traffic congestion, road safety, and fuel waste. Collecting vehicles’ speed information is an effective way to monitor the traffic conditions and avoid vehicles’ congestion, however it may threaten vehicles’ location and trajectory privacy. Motivated by the fact that traffic monitoring does not need to know each individual vehicle’s speed and the average speed would be sufficient, we propose a privacy-preserving traffic monitoring (PPTM) scheme to aggregate vehicles’ speeds at different locations. In PPTM, the roadside unit (RSU) collects vehicles’ speed information at multiple road segments, and further cooperates with a service provider to calculate the average speed information for every road segment. To preserve vehicles’ privacy, both homomorphic Paillier cryptosystem and super-increasing sequence are adopted. A comprehensive security analysis indicates that the proposed PPTM can preserve vehicles’ identities, speeds, locations, and trajectories privacy from being disclosed. In addition, extensive simulations are conducted to validate the effectiveness and efficiency of the proposed PPTM scheme.
    • A protocol for safe lithiation reactions using organolithium reagents

      Gau, MR; Zdilla, MJ; Zdilla, Michael|0000-0003-0212-2557 (2016-11-12)
      © 2016 Journal of Visualized Experiments. Organolithium reagents are powerful tools in the synthetic chemist's toolbox. However, the extreme pyrophoric nature of the most reactive reagents warrants proper technique, thorough training, and proper personal protective equipment. To aid in the training of researchers using organolithium reagents, a thorough, step-by-step protocol for the safe and effective use of tert-butyllithium on an inert gas line or within a glovebox is described. As a model reaction, preparation of lithium tert-butyl amide by the reaction of tert-butyl amine with one equivalent of tert-butyl lithium is presented.
    • A qualitative study of the aspirations and challenges of low-income mothers in feeding their preschool-aged children

      Herman, AN; Malhotra, K; Wright, G; Fisher, JO; Whitaker, RC (2012-11-16)
      Background: The prevalence of obesity among preschool-aged children has increased, especially among those in low-income households. Two promising behavioral targets for preventing obesity include limiting children's portion sizes and their intake of foods high in solid fats and/or added sugars, but these approaches have not been studied in low-income preschoolers in the home setting. The purpose of this study was to understand the contextual factors that might influence how low-income mothers felt about addressing these behavioral targets and mothers' aspirations in feeding their children.Methods: We recruited 32 English-speaking women in Philadelphia, Pennsylvania who were eligible for the Supplemental Nutrition Assistance Program and who were the biologic mothers of children 36 to 66 months of age. Each mother participated in 1 of 7 focus groups and completed a brief socio-demographic questionnaire. Focus group questions centered on eating occasions, foods and drinks consumed in the home, and portion sizes. Each focus group lasted 90 minutes and was digitally recorded and transcribed verbatim. Three authors independently identified key themes and supporting quotations. Themes were condensed and modified through discussion among all authors. Results: Thirty-one mothers identified themselves as black, 15 had a high school education or less, and 22 lived with another adult. Six themes emerged, with three about aspirations mothers held in feeding their children and three about challenges to achieving these aspirations. Mothers' aspirations were to: 1) prevent hyperactivity and tooth decay by limiting children's sugar intake, 2) use feeding to teach their children life lessons about limit setting and structure, and 3) be responsive to children during mealtimes to guide decisions about portions. Especially around setting limits with sweets and snacks, mothers faced the challenges of: 1) being nagged by children's food requests, 2) being undermined by other adults in the family, and 3) having bad memories from childhood that made it hard to deny children's food requests. Conclusions: Although the primary aspirations of low-income mothers in feeding their preschool-aged children were not focused on children's weight, these aspirations were compatible with obesity prevention strategies to limit children's portion sizes and their intake of solid fats and/or added sugars. © 2012 Herman et al.; licensee BioMed Central Ltd.