Chromatographic Separation: A Versatile Strategy to Prepare Discrete and Well-Defined Polymer Libraries.

ConspectusThe preparation of discrete and well-defined polymers is an emerging strategy for emulating the remarkable precision achieved by macromolecular synthesis in nature. Although modern controlled polymerization techniques have unlocked access to a cornucopia of materials spanning a broad range of monomers, molecular weights, and architectures, the word "controlled" is not to be confused with "perfect". Indeed, even the highest-fidelity polymerization techniques─yielding molar mass dispersities in the vicinity of D = 1.05─unavoidably create a considerable degree of structural and/or compositional dispersity due to the statistical nature of chain growth. Such dispersity impacts many of the properties that researchers seek to control in the design of soft materials.The development of strategies to minimize or entirely eliminate dispersity and access molecularly precise polymers therefore remains a key contemporary challenge. While significant advances have been made in the realm of iterative synthetic methods that construct oligomers with an exact molecular weight, head-to-tail connectivity, and even stereochemistry via small-molecule organic chemistry, as the word "iterative" suggests, these techniques involve manually propagating monomers one reaction at a time, often with intervening protection and deprotection steps. As a result, these strategies are time-consuming, difficult to scale, and remain limited to lower molecular weights. The focus of this Account is on an alternative strategy that is more accessible to the general scientific community because of its simplicity, versatility, and affordability: chromatography. Researchers unfamiliar with the intricacies of synthesis may recall being exposed to chromatography in an undergraduate chemistry lab. This operationally simple, yet remarkably powerful, technique is most commonly encountered in the purification of small molecules through their selective (differential) adsorption to a column packed with a low-cost stationary phase, usually silica. Because the requisite equipment is readily available and the actual separation takes little time (on the order of 1 h), chromatography is used extensively in small-molecule chemistry throughout industry and academia alike. It is, therefore, perhaps surprising that similar types of chromatography are not more widely leveraged in the field of polymer science as well.Here, we discuss recent advances in using chromatography to control the structure and properties of polymeric materials. Emphasis is placed on the utility of an adsorption-based mechanism that separates polymers based on polarity and composition at tractable (gram) scales for materials science, in contrast to size exclusion, which is extremely common but typically analyzes very small quantities of a sample (∼1 mg) and is limited to separating by molar mass. Key concepts that are highlighted include (1) the separation of low-molecular-weight homopolymers into discrete oligomers (D = 1.0) with precise chain lengths and (2) the efficient fractionation of block copolymers into high-quality and widely varied libraries for accelerating materials discovery. In summary, the authors hope to convey the exciting possibilities in polymer science afforded by chromatography as a scalable, versatile, and even automated technique that unlocks new avenues of exploration into well-defined materials for a diverse assortment of researchers with different training and expertise.

Cylinders-in-Undulating-Lamellae Morphology from ABC Bottlebrush Block Terpolymers.

Block polymer self-assembly affords a versatile bottom-up strategy to develop materials with the desired properties dictated by specific symmetries and dimensions. Owing to distinct properties compared with linear counterparts, bottlebrush block polymers with side chains densely grafted on a backbone have attracted extensive attention. However, the morphologies found in bottlebrush block polymers so far are limited, and only lamellar and cylindrical ordered phases have been reported in diblock bottlebrushes. The absence of complex morphologies, such as networks, might originate from the intrinsically stiff backbone architecture. We experimentally investigated the morphologies of nonfrustrated ABC bottlebrush block terpolymers, based on two chemistries, poly(ethylene-alt-propylene)-b-polystyrene-b-poly(dl-lactic acid) (PEP-PS-PLA) and PEP-b-PS-b-poly(ethylene oxide) (PEP-PS-PEO), synthesized by ring-opening metathesis polymerization of norbornene-terminated macromonomers. Structural characterization based on small-angle X-ray scattering and transmission electron microscopy measurements revealed an unprecedented cylinders-in-undulating-lamellae (CUL) morphology with p2 symmetry for both systems. Additionally, automated liquid chromatography was employed to fractionate the PEP-PS-PLA bottlebrush polymer, leading to fractions with a spectrum of morphologies, including the CUL. These findings underscore the significance of macromolecular dispersity in nominally narrow dispersity bottlebrush polymers while demonstrating the power of this fractionation technique.

Accelerated Prediction of Phase Behavior for Block Copolymer Libraries Using a Molecularly Informed Field Theory.

Solution formulations involving polymers are the basis for a wide range of products spanning consumer care, therapeutics, lubricants, adhesives, and coatings. These multicomponent systems typically show rich self-assembly and phase behavior that are sensitive to even small changes in chemistry and composition. Longstanding computational efforts have sought techniques for predictive modeling of formulation structure and thermodynamics without experimental guidance, but the challenges of addressing the long time scales and large length scales of self-assembly while maintaining chemical specificity have thwarted the emergence of general approaches. As a consequence, current formulation design remains largely Edisonian. Here, we present a multiscale modeling approach that accurately predicts, without any experimental input, the complete temperature-concentration phase diagram of model diblock polymers in solution, as established postprediction through small-angle X-ray scattering. The methodology employs a strategy whereby atomistic molecular dynamics simulations is used to parametrize coarse-grained field-theoretic models; simulations of the latter then easily surmount long equilibration time scales and enable rigorous determination of solution structures and phase behavior. This systematic and predictive approach, accelerated by access to well-defined block copolymers, has the potential to expedite in silico screening of novel formulations to significantly reduce trial-and-error experimental design and to guide selection of components and compositions across a vast range of applications.

Tailoring Writability and Performance of Star Block Copolypeptides Hydrogels through Side-Chain Design.

Shear-recoverable hydrogels based on block copolypeptides with rapid self-recovery hold potential in extrudable and injectable 3D-printing applications. In this work, a series of 3-arm star-shaped block copolypeptides composed of an inner hydrophilic poly(l-glutamate) domain and an outer ß-sheet forming domain is synthesized with varying side chains and block lengths. By changing the ß-sheet forming domains, hydrogels with diverse microstructures and mechanical properties are prepared and structure-function relationships are determined using scattering and rheological techniques. Differences in the properties of these materials are amplified during direct-ink writing with a strong correlation observed between printability and material chemistry. Significantly, it is observed that non-canonical ß-sheet blocks based on phenyl glycine form more stable networks with superior mechanical properties and writability compared to widely used natural amino acid counterparts. The versatile design available through block copolypeptide materials provides a robust platform to access tunable material properties based solely on molecular design. These systems can be exploited in extrusion-based applications such as 3D-printing without the need for additives.

Boundary layer hydrodynamics of patchy biofilms.

Algal biofilms, ubiquitous in aquatic systems, reduce the performance of engineered systems and alter ecosystem processes. Biofilm morphology is dynamic throughout community development, with patchiness occurring due to periodic sloughing, but little is known about how community level physical structure affects hydrodynamics. This study uses high resolution particle image velocimetry (PIV) to examine spatially explicit turbulence over sparse, uniform and patchy biofilm at turbulent Reynolds numbers. All biofilms increase the near-bed turbulence production, Reynolds shear stress, and rotational flow compared to a smooth wall, and non-uniform biofilms have the greatest increase in these parameters, compared with a uniform or sparse biofilm. However, a higher drag coefficient over uniform biofilm compared with non-uniform biofilm indicates that percent coverage (the amount of area covered by the biofilm) is a useful predictor of a biofilm's relative effect on the total drag along surfaces, and in particular the effect on ship performance.

Video-based communication assessment for weight management counseling training in medical residents: a mixed methods study.

BACKGROUND: Physician delivered weight management counseling (WMC) occurs infrequently and physicians report lack of training and poor self-efficacy. The purpose of this study was to develop and test the Video-based Communication Assessment (VCA) for weight management counseling (WMC) training in medical residents. METHODS: This study was a mixed methods pilot conducted in 3 phases. First, we created five vignettes based on our prior data and expert feedback, then administered the vignettes via the VCA to Internal Medicine categorical residents (n = 16) from a University Medical School. Analog patients rated responses and also provided comments. We created individualized feedback reports which residents were able to view on the VCA. Lastly, we conducted debriefing interviews with the residents (n = 11) to obtain their feedback on the vignettes and personalized feedback. Interviews were transcribed, and we used thematic analysis to generate and apply codes, followed by identifying themes. RESULTS: Descriptive statistics were calculated and learning points were created for the individualized feedback reports. In VCA debriefing interviews with residents, five themes emerged: 1) Overall the VCA was easy to use, helpful and more engaging than traditional learning and assessment modes, 2) Patient scenarios were similar to those encountered in the clinic, including diversity, health literacy and different stages of change, 3) The knowledge, skills, and reminders from the VCA can be transferred to practice, 4) Feedback reports were helpful, to the point and informative, including the exemplar response of how to best respond to the scenario, and 5) The VCA provide alternatives and practice scenarios to real-life patient situations when they aren't always accessible. CONCLUSIONS: We demonstrated the feasibility and acceptability of the VCA, a technology delivered platform, for delivering WMC to residents. The VCA exposed residents to diverse patient experiences and provided potential opportunities to tailor providers responses to sociological and cultural factors in WMC scenarios. Future work will examine the effect of the VCA on WMC in actual clinical practice.

Emergence of Hexagonally Close-Packed Spheres in Linear Block Copolymer Melts.

The hexagonally close-packed (HCP) sphere phase is predicted to be stable across a narrow region of linear block copolymer phase space, but the small free energy difference separating it from face-centered cubic spheres usually results in phase coexistence. Here, we report the discovery of pure HCP spheres in linear block copolymer melts with A = poly(2,2,2-trifluoroethyl acrylate) ("F") and B = poly(2-dodecyl acrylate) ("2D") or poly(4-dodecyl acrylate) ("4D"). In 4DF diblocks and F4DF triblocks, the HCP phase emerges across a substantial range of A-block volume fractions (circa fA = 0.25-0.30), and in F4DF, it forms reversibly when subjected to various processing conditions which suggests an equilibrium state. The time scale associated with forming pure HCP upon quenching from a disordered liquid is intermediate to the ordering kinetics of the Frank-Kasper σ and A15 phases. However, unlike σ and A15, HCP nucleates directly from a supercooled liquid or soft solid without proceeding through an intermediate quasicrystal. Self-consistent field theory calculations indicate the stability of HCP is intimately tied to small amounts of molar mass dispersity (D); for example, an HCP-forming F4DF sample with fA = 0.27 has an experimentally measured D = 1.04. These insights challenge the conventional wisdom that pure HCP is difficult to access in linear block copolymer melts without the use of blending or other complex processing techniques.

Phenotype and treatment of elderly onset compared with younger onset rheumatoid arthritis patients in international daily practice.

OBJECTIVE: To identify possible differences in baseline characteristics, initial treatment and treatment response between RA patient subgroups based on age at disease onset. METHODS: Daily practice data from the worldwide METEOR registry were used. Patients (7912) were stratified into three age-groups (age at disease diagnosis <45 years, 45-65 years, >65 years). Initial treatment was compared between the different age-groups. With Cox regression analyses the effect of age-group on time-to-switch from first to second treatment was investigated, and with linear mixed models differences in response to treatment (DAS and HAQ) between the age-groups were assessed, after correction for potential confounders. RESULTS: The >65 years age-group included more men, and more seronegative RA with somewhat higher inflammatory markers. Initial treatment choices differed only slightly between the age-groups, and the time-to-switch from initial treatment to the next was similar. DAS and HAQ improvement were dependent on the age-group, reflected by a significant interaction between age-group and outcome. The stratified analysis showed a difference of -0.02 and -0.05 DAS points and, -0.01 and 0.02 HAQ points per month in the <45 and 45-65 years age-groups as compared with the >65 year age group, a difference that did not seem clinically relevant. CONCLUSION: In this international study on worldwide clinical practice, patients with RA onset >65 years include more men and seronegative arthritis, and were initially treated slightly differently than younger patients. We observed no clinically relevant differences in timing of a next treatment step, or response to treatment measured by DAS and HAQ.

Information Needs for Treatment Decision-making of Hematopoietic Cell Transplant Patients 65 Years or Older and Caregivers.

Hematopoietic cell transplantation (HCT) is a complex and potentially life-threatening treatment option for patients with hematologic malignant and non-malignant diseases. Advances have made HCT a potentially curative treatment option for patients 65 years of age and older (older patients), and patient education resources should be adapted to meet their needs. To better understand the information needs of older patients and their caregivers for HCT treatment decision-making, the National Marrow Donor Program® (NMDP)/Be The Match® conducted a qualitative comprehensive needs assessment. Focus groups, offered in person or by phone, were conducted with older HCT patients and primary caregivers of older HCT patients at three transplant centers in the USA that were selected based on the number of older adults treated and geographic diversity. The one-hour, semi-structured discussions were recorded and transcribed verbatim. The analysis was performed with the NVivo 10 software for identification of conceptual themes. Five telephone and six in person focus groups of patients (n = 35) and caregivers (n = 10) were conducted. Themes that emerged included the following: (1) the need for tailored resources with age-specific recovery expectations; (2) the need for the right amount of information at the right times; and (3) the benefit of peer support. Effective patient education supports learning and treatment decision-making. As HCT increasingly becomes a treatment option for older patients, tailored educational resources are needed. These focus group results can inform and guide the development of new educational resources for older adults with hematologic diseases considering and planning for HCT.

A Conceptual Framework and Key Research Questions in Educational Needs of Blood and Marrow Transplantation Patients, Caregivers, and Families.

Patient, caregiver, and family education and support was 1 of 6 key areas of interest identified by the National Marrow Donor Program/Be The Match 2-year project to prioritize patient-centered outcomes research (PCOR) goals for the blood and marrow transplantation (BMT) community. PCOR focuses on research to help patients and their caregivers make informed decisions about health care. Therefore, each area of interest was assigned to a working group with broad representation, including patients, caregivers, and clinicians. Each working group was charged with identifying gaps in knowledge and making priority recommendations for critical research to fill those gaps. The report from this working group presents a conceptual framework to address gaps in knowledge regarding patient and caregiver education in BMT and recommendations for priority research questions on this topic.

Tailoring a Survivorship Care Plan: Patient and Provider Preferences for Recipients of Hematopoietic Cell Transplantation.

This study aimed to develop a survivorship care plan (SCP) that can be individualized to facilitate long-term follow-up care of hematopoietic cell transplantation (HCT) survivors. A sample SCP was developed that included 2 documents: a treatment summary and preventive care recommendations that combined data on treatment exposures routinely submitted by HCT centers to the Center for International Blood and Marrow Transplant Research (CIBMTR) with long-term follow-up guidelines. Focus groups were conducted by phone to characterize the critical patient-centered elements of the SCP. Focus group eligibility criteria included (1) adult patients >1 year post-HCT and their caregivers (3 groups; n = 22), (2) HCT physicians and advanced practice providers (APPs) (2 groups; n = 14), (3) HCT nurses and social workers (4 groups; n = 17), and (4) community health care professionals (3 groups; n = 24). Transcripts were analyzed for saturation of key themes using NVivo 10 software. Patients and caregivers suggested combining the treatment summary and care guidelines into a single document. They also requested sections on sexual and emotional health and the immune system. Providers wanted the treatment summary to focus only on what they absolutely must know. Themes were similar across healthcare professionals, although screening for psychosocial issues was emphasized more by the nurses and social workers. All preferred to receive the SCP electronically; however, hardcopy was considered necessary for some patients. All felt that the SCP would facilitate appropriate post-HCT care. This study highlights the need for an SCP instrument to facilitate HCT survivorship care. Furthermore, it demonstrates the feasibility and value of engaging HCT recipients, caregivers, and providers in developing an SCP. Their feedback was incorporated into a final SCP that was subsequently tested in a randomized trial.

Addressing Knowledge Gaps in Acute Myeloid Leukemia to Improve Referral for Hematopoietic Cell Transplantation Consultation.

BACKGROUND: Outcomes after hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) are better when HCT is performed during first complete remission (CR1). This study aimed to identify and address knowledge gaps that affect the timely referral of patients for HCT consultation. METHODS: A mixed-methods educational needs assessment included a national survey and focus groups consisting of hematologists/oncologists. An educational intervention of 3 webinars addressed identified knowledge gaps. RESULTS: A total of 150 hematologists/oncologists were recruited for the survey, of whom 20 participated in focus groups. Physicians in practice 0 to 10 years were 4.2 times more likely to refer for HCT consultation in CR1 than those with >10 years in practice (P=.0027). Physicians seeing ≤10 patients with AML in the past year were 3.7 times more likely to refer for HCT consultation in CR1 than those seeing >10 patients (P=.0028). Knowledge gaps included (1) improper classification of molecular/cytogenetic results for risk stratification, (2) lack of understanding that disease stage impacts outcomes, and (3) use of chronologic age alone for referral decision-making. Combined attendance for the webinars was 1,098 clinicians; >74% of participants indicated that they would apply the knowledge they gained in clinical practice. Trends were observed toward improvement in identifying favorable-risk AML, from 48% to 60% (n=85; P=.12); improvement in identifying 2 poor-risk cytogenetic/molecular abnormalities, with the percentage of respondents indicating chromosome 7 deletion increasing from 51% to 70% (n=53; P=.05) and that of respondents indicating TP53 mutation increasing from 42% to 62% (n=62; P=.03); and improvement in identifying which patients with AML aged >60 years were most likely to benefit from HCT based on cytogenetic/molecular features, with the percentage of correct responses increasing from 66% to 81% (n=62; P=.07). CONCLUSIONS: The webinars met the educational needs of learners and improved knowledge gaps. This study provided novel insights into the learning needs of clinicians who care for patients with AML and a roadmap for future educational interventions.

Caregiver availability and patient access to hematopoietic cell transplantation: social worker perspectives inform practice.

PURPOSE: Hematopoietic cell transplantation (HCT) often involves a long hospitalization and recovery period, with patients generally required to have a caregiver. This study aimed to identify transplant center (TC) requirements for a caregiver, describe challenges that impact caregiver availability, and identify potential solutions. METHODS: An exploratory sequential mixed-methods approach was used. Qualitative data was obtained from focus groups of TC social workers in the United States (US) (three focus groups; n = 15 total participants). Results informed the development of a national, web-based survey that was administered to the primary social worker contact at TCs in the National Marrow Donor Program (NMDP)/Be The Match Network (n = 133). RESULTS: Respondents included social workers from adult (n = 47) and pediatric (n = 19) TCs (response rate = 49%). The majority (89%) of both adult and pediatric TCs required a caregiver for a patient to proceed to transplant, but requirements varied in length of time, formality, transplant type, and HCT setting. Regardless of transplant type or patient population, social workers identified loss of caregiver income as the greatest challenge to caregiver availability, with the most common solution being allowing patients to have multiple caregivers throughout the transplant course. DISCUSSION: Caregiver availability is an important concern for patients considering and receiving HCT, and may be a barrier proceeding to HCT when a caregiver is unavailable. Results from this study highlight caregiver availability barriers and solutions of TCs across the US. These results can inform TCs about other center experiences with caregiver availability and identify potential practice changes for individual TCs.

System- and Unit-Level Care Quality Outcome Improvements After Integrating Clinical Nurse Leaders Into Frontline Care Delivery.

OBJECTIVE: This study determined whether 1 health system's frontline nursing model redesign to integrate clinical nurse leaders (CNLs) improved care quality and outcome score consistency. METHODS: Interrupted time-series design was used to measure patient satisfaction with 7 metrics before and after formally integrating CNLs into a Michigan healthcare system. Analysis generated estimates of quality outcome: a) change point; b) level change; and c) variance, pre-post implementation. RESULTS: The lowest-performing unit showed significant increases in quality scores, but there were no significant increases at the hospital level. Quality metric consistency increased significantly for every indicator at the hospital and unit level. CONCLUSIONS: To our knowledge, this is the 1st study quantifying quality outcome consistency before and after nursing care delivery redesign with CNLs. The significant improvement suggests the CNL care model is associated with production of stable clinical microsystem practices that help to reduce clinical variability, thus improving care quality.

Advancing the clinical nurse leader model through academic-practice-policy partnership.

The nursing profession is tasked with identifying and evaluating models of care with potential to add value to health care delivery. In consideration of this goal, we describe the Clinical Nurse Leader (CNL) initiative and the activities of a national-level CNL research collaborative. The CNL initiative, launched by the American Association of Colleges of Nursing in collaboration with education and healthcare leaders, has delineated CNL education curriculum and practice competencies, and fostered the creation of academic-practice-policy partnerships to pilot CNL integration into frontline nursing care delivery. The partnership has evolved into an Agency for Healthcare Research and Quality affiliate practice-based research network, the CNL Research Collaborative, which links research, policy, education, and practice stakeholders to advance the CNL evidence base. We summarize foundational CNLRC research to explain CNL practice, quantify CNL effectiveness, and bring clarity to how CNLs can be implemented to consistently influence care, quality, and safety.

Perceived Workforce Challenges among Clinical Social Workers in Hematopoietic Cell Transplantation Programs.

Clinical social workers are psychosocial care experts who provide interventions that aim to address the emotional, relational, financial, and logistical challenges that arise throughout the hematopoietic cell transplantation (HCT) treatment and recovery process. Interventions that contribute to better patient outcomes can include cognitive behavioral therapy and counseling for adaptation to illness, family planning for 24/7 caregiver availability and strategies to support patient activities of daily living, instruction on guided imagery and relaxation techniques for symptom management and to decrease anxiety, psychoeducation on the treatment trajectory, and linkage with financial resources. A Social Work Workforce Group (SWG) was established through the System Capacity Initiative, led by the National Marrow Donor Program/Be The Match, to characterize the current social work workforce capacity and challenges. The SWG conducted a web-based survey of HCT clinical social workers in the United States. The response rate was 57% (n = 90), representing 76 transplant centers. Survey results indicated that the clinical social worker role and scope of practice varies significantly between centers; less than half of respondents reported that their clinical social work expertise was used to its fullest potential. With an estimated 3-fold increase in HCT patient volume by 2020, the need for specialized psychosocial health services will increase. The SWG makes recommendations to build capacity for the psychosocial care of HCT patients and to more fully integrate the social worker as a core member of the HCT team. The SWG created a Blood and Marrow Transplant (BMT) Clinical Social Worker role description that can be used by transplant centers to educate healthcare professionals, benchmark utilization of clinical social workers, and improve comprehensive psychosocial health programs.

Burnout, Moral Distress, Work-Life Balance, and Career Satisfaction among Hematopoietic Cell Transplantation Professionals.

A projected shortage of hematopoietic cell transplantation (HCT) health professionals was identified as a major issue during the National Marrow Donor Program/Be The Match System Capacity Initiative. Work-related distress and work-life balance were noted to be potential barriers to recruitment/retention. This study examined these barriers and their association with career satisfaction across HCT disciplines. A cross-sectional, 90-item, web-based survey was administered to advanced practice providers, nurses, physicians, pharmacists, and social workers in 2015. Participants were recruited from membership lists of 6 professional groups. Burnout (measured with the Maslach Burnout Inventory subscales of emotional exhaustion and depersonalization) and moral distress (measured by Moral Distress Scale-Revised) were examined to identify work-related distress. Additional questions addressed demographics, work-life balance, and career satisfaction. Of 5759 HCT providers who received an individualized invitation to participate, 914 (16%) responded; 627 additional participants responded to an open link survey. Significant differences in demographic and practice characteristics existed across disciplines (P < .05). The prevalence of burnout differed across disciplines (P < .05) with an overall prevalence of 40%. Over one-half of pharmacists had burnout, whereas social workers had the lowest prevalence at less than one-third. Moral distress scores ranged from 0 to 336 and varied by discipline (P < .05); pharmacists had the highest mean score (62.9 ± 34.8) and social workers the lowest (42.7 ± 24.4). In multivariate and univariate analyses, variables contributing to burnout varied by discipline; however, moral distress was a significant contributing factor for all providers. Those with burnout were more likely to report inadequate work-life balance and a low level of career satisfaction; however, overall there was a high level of career satisfaction across disciplines. Burnout, moral distress, and inadequate work-life balance existed at a variable rate in all HCT disciplines, yet career satisfaction was high. These results suggest specific areas to address in the work environment for HCT health professionals, especially the need for relief of moral distress and a greater degree of personal time. As the creation of healthy work environments is increasingly emphasized to improve quality care and decrease costs, these findings should be used by HCT leadership to develop interventions that mitigate work-related distress and in turn foster recruitment and retention of HCT providers.

Engaging Patients in Setting a Patient-Centered Outcomes Research Agenda in Hematopoietic Cell Transplantation.

The goal of patient-centered outcomes research (PCOR) is to help patients and those who care for them make informed decisions about healthcare. However, the clinical research enterprise has not involved patients, caregivers, and other nonproviders routinely in the process of prioritizing, designing, and conducting research in hematopoietic cell transplantation (HCT). To address this need the National Marrow Donor Program/Be The Match engaged patients, caregivers, researchers, and other key stakeholders in a 2-year project with the goal of setting a PCOR agenda for the HCT community. Through a collaborative process we identified 6 major areas of interest: (1) patient, caregiver, and family education and support; (2) emotional, cognitive, and social health; (3) physical health and fatigue; (4) sexual health and relationships; (5) financial burden; and (6) models of survivorship care delivery. We then organized into multistakeholder working groups to identify gaps in knowledge and make priority recommendations for critical research to fill those gaps. Gaps varied by working group, but all noted that a historical lack of consistency in measures use and patient populations made it difficult to compare outcomes across studies and urged investigators to incorporate uniform measures and homogenous patient groups in future research. Some groups advised that additional pre-emptory work is needed before conducting prospective interventional trials, whereas others were ready to proceed with comparative clinical effectiveness research studies. This report presents the results of this major initiative and makes recommendations by working group on priority questions for PCOR in HCT.

Soluble Zwitterionic Poly(sulfobetaine) Destabilizes Proteins.

The widespread interest in neutral, water-soluble polymers such as poly(ethylene glycol) (PEG) and poly(zwitterions) such as poly(sulfobetaine) (pSB) for biomedical applications is due to their widely assumed low protein binding. Here we demonstrate that pSB chains in solution can interact with proteins directly. Moreover, pSB can reduce the thermal stability and increase the protein folding cooperativity relative to proteins in buffer or in PEG solutions. Polymer-dependent changes in the tryptophan fluorescence spectra of three structurally-distinct proteins reveal that soluble, 100 kDa pSB interacts directly with all three proteins and changes both the local polarity near tryptophan residues and the protein conformation. Thermal denaturation studies show that the protein melting temperatures decrease by as much as ∼1.9 °C per weight percent of polymer and that protein folding cooperativity increases by as much as ∼130 J mol-1 K-1 per weight percent of polymer. The exact extent of the changes is protein-dependent, as some proteins exhibit increased stability, whereas others experience decreased stability at high soluble pSB concentrations. These results suggest that pSB is not universally protein-repellent and that its efficacy in biotechnological applications will depend on the specific proteins used.

Roughness effects of diatomaceous slime fouling on turbulent boundary layer hydrodynamics.

Biofilm fouling significantly impacts ship performance. Here, the impact of biofilm on boundary layer structure at a ship-relevant, low Reynolds number was investigated. Boundary layer measurements were performed over slime-fouled plates using high resolution particle image velocimetry (PIV). The velocity profile over the biofilm showed a downward shift in the log-law region (ΔU+), resulting in an effective roughness height (ks) of 8.8 mm, significantly larger than the physical thickness of the biofilm (1.7 ± 0.5 mm) and generating more than three times as much frictional drag as the smooth-wall. The skin-friction coefficient, Cf, of the biofilm was 9.0 × 10-3 compared with 2.9 × 10-3 for the smooth wall. The biofilm also enhances turbulent kinetic energy (tke) and Reynolds shear stress, which are more heterogeneous in the streamwise direction than smooth-wall flows. This suggests that biofilms increase drag due to high levels of momentum transport, likely resulting from protruding streamers and surface compliance.