Structure-Function Relationship of Iron Oxide Nanoflowers: Optimal Sizes for Magnetic Hyperthermia Depending on Alternating Magnetic Field Conditions.

Iron oxide nanoflowers (IONFs) that display singular magnetic properties can be synthesized through a polyol route first introduced almost 2 decades ago by Caruntu et al, presenting a multi-core morphology in which several grains (around 10 nm) are attached together and sintered. These outstanding properties are of great interest for magnetic field hyperthermia, which is considered as a promising therapy against cancer. Although of significantly smaller diameter, the specific adsorption rate (SAR) of IONFs reach values as large as for "magnetosomes" that are natural magnetic nanoparticles typically ~40 nm found in certain bacteria, which can be grown artificially but with much lower yield compared to chemical synthesis such as the polyol route. This work aims at better understanding the structure-property relationships, linking the internal IONF nanostructure as observed by HR-TEM to their magnetic properties. A library of mono- and multicore IONFs is presented, with diameters ranging from 11 to 30 nm in a narrow size distribution. More particularly, by relating their structural features to their magnetic properties investigated by utilizing AC magnetometry over a wide range of alternating magnetic field conditions, we showed that the SAR values of all synthesized batches vary with overall diameter and number of constituting cores.

Linear Block Copolymer Synthesis.

Block copolymers form the basis of the most ubiquitous materials such as thermoplastic elastomers, bridge interphases in polymer blends, and are fundamental for the development of high-performance materials. The driving force to further advance these materials is the accessibility of block copolymers, which have a wide variety in composition, functional group content, and precision of their structure. To advance and broaden the application of block copolymers will depend on the nature of combined segmented blocks, guided through the combination of polymerization techniques to reach a high versatility in block copolymer architecture and function. This review provides the most comprehensive overview of techniques to prepare linear block copolymers and is intended to serve as a guideline on how polymerization techniques can work together to result in desired block combinations. As the review will give an account of the relevant procedures and access areas, the sections will include orthogonal approaches or sequentially combined polymerization techniques, which increases the synthetic options for these materials.

Block Copolymers of Polyolefins with Polyacrylates: Analyzing and Improving the Blocking Efficiencies Using MILRad/ATRP Approach.

Despite their industrial ubiquity, polyolefin-polyacrylate block copolymers are challenging to synthesize due to the distinct polymerization pathways necessary for respective blocks. This study utilizes MILRad, metal-organic insertion light-initiated radical polymerization, to synthesize polyolefin-b-poly(methyl acrylate) copolymer by combining palladium-catalyzed insertion-coordination polymerization and atom transfer radical polymerization (ATRP). Brookhart-type Pd complexes used for the living polymerization of olefins are homolytically cleaved by blue-light irradiation, generating polyolefin-based macroradicals, which are trapped with functional nitroxide derivatives forming ATRP macroinitiators. ATRP in the presence of Cu(0), that is, supplemental activators and reducing agents , is used to polymerize methyl acrylate. An increase in the functionalization efficiency of up to 71% is demonstrated in this study by modifying the light source and optimizing the radical trapping condition. Regardless of the radical trapping efficiency, essentially quantitative chain extension of polyolefin-Br macroinitiator with acrylates is consistently demonstrated, indicating successful second block formation.

Tandem Living Insertion and Controlled Radical Polymerization for Polyolefin-Polyvinyl Block Copolymers.

Practical synthesis of polyolefin-polyvinyl block copolymers remains a challenge for transition-metal catalyzed polymerizations. Common approaches functionalize polyolefins for post-radical polymerization via insertion methods, yet sacrifice the livingness of the olefin polymerization. This work identifies an orthogonal radical/spin coupling technique which affords tandem living insertion and controlled radical polymerization. The broad tolerance of this coupling technique has been demonstrated for diverse radical/spin traps such as 2,2,5-trimethyl-4-phenyl-3-azahexane-3-nitroxide (TIPNO), 1-oxyl-(2,2,6,6-tetramethylpiperidine) -4-yl-α-bromoisobutyrate (TEMPO-Br), and N-tert-butyl-α-phenylnitrone (PBN). Subsequent controlled radical polymerization is demonstrated with nitroxide-mediated polymerization (NMP) and atom transfer radical polymerization (ATRP), yielding polyolefin-polyvinyl di- and triblock copolymers (D<1.3) with acrylic, vinylic and styrenic segments. These findings highlight radical trapping as an approach to expand the scope of polyolefin-functionalization techniques to access polyolefin macroinitiators.

Dual Polymerization Pathway for Polyolefin-Polar Block Copolymer Synthesis via MILRad: Mechanism and Scope.

This work explores the mechanism whereby a cationic diimine Pd(II) complex combines coordination insertion and radical polymerization to form polyolefin-polar block copolymers. The initial requirement involves the insertion of a single acrylate monomer into the Pd(II)-polyolefin intermediates, which generate a stable polymeric chelate through a chain-walking mechanism. This thermodynamically stable chelate was also found to be photochemically inactive, and a unique mechanism was discovered which allows for radical polymerization. Rate-determining opening of the chelate by an ancillary ligand followed by additional chain walking allows the metal to migrate to the α-carbon of the acrylate moiety. Ultimately, the molecular parameters necessary for blue-light-triggered Pd-C bond homolysis from this α-carbon to form a carbon-centered macroradical species were established. This intermediate is understood to initiate free radical polymerization of acrylic monomers, thereby facilitating block copolymer synthesis from a single Pd(II) complex. Key intermediates were isolated and comprehensively characterized through exhaustive analytical methods which detail the mechanism while confirming the structural integrity of the polyolefin-polar blocks. Chain walking combined with blue-light irradiation functions as the mechanistic switch from coordination insertion to radical polymerization. On the basis of these discoveries, robust di- and triblock copolymer syntheses have been demonstrated with olefins (ethylene and 1-hexene) which produce amorphous or crystalline blocks and acrylics (methyl acrylate, ethyl acrylate, n-butyl acrylate, and methyl methacrylate) in broad molecular weight ranges and compositions, yielding AB diblocks and BAB triblocks.

Addressing the quality of submissions to ClinicalTrials.gov for registration and results posting: The use of a checklist.

BACKGROUND: US Federal regulations since the late 1990s have required registration of some clinical trials and submission of results for some of these trials on a public registry, ClinicalTrials.gov. The quality of the submissions made to ClinicalTrials.gov determines the duration of the Quality Control review, whether the submission will pass the review (success), and how many review cycles it will take for a study to be posted. Success rate for all results submitted to ClinicalTrials.gov is less than 25%. To increase the success of investigators' submissions and meet the requirements of registration and submission of results in a timely fashion, the Johns Hopkins ClinicalTrials.gov Program implemented a policy to review all studies for quality before submission. To standardize our review for quality, minimize inter-reviewer variability, and have a tool for training new staff, we developed a checklist. METHODS: The Program staff learned from major comments received from ClinicalTrials.gov and also reviewed the Protocol Registration and Results System review criteria for registration and results to fully understand how to prepare studies to pass Quality Control review. These were summarized into bulleted points and incorporated into a checklist used by Program staff to review studies before submission. RESULTS: In the period before the introduction of the checklist, 107 studies were submitted for registration with a 45% (48/107) success rate, a mean (SD) of 18.9 (26.72) days in review, and 1.74 (0.78) submission cycles. Results for 44 records were submitted with 11% (5/44) success rate, 115.80 (129.33) days in review, and 2.23 (0.68) submission cycles. In the period after the checklist, 104 studies were submitted for registration with 80% (83/104) success rate, 2.12 (3.85) days in review, and 1.22 (0.46) submission cycles. Results for 22 records were submitted with 41% (9/22) success rate, 39.27 (19.84) days in review, and 1.64 (0.58) submission cycles. Of the 44 results submitted prior to the checklist, 30 were Applicable or Probable Applicable Clinical Trials, with 10% (3/30) being posted within 30 days as required of the National Institutes of Health. For the 22 results submitted after the checklist, 17 were Applicable or Probable Applicable Clinical Trials, with 47% (8/17) being posted within 30 days of submission. These pre- and post-checklist differences were statistically significant improvements. CONCLUSION: The checklist has substantially improved our success rate and contributed to a reduction in the review days and number of review cycles. If Academic Medical Centers and industry will adopt or create a similar checklist to review their studies before submission, the quality of the submissions can be improved and the duration of review can be minimized.

Olefins and Vinyl Polar Monomers: Bridging the Gap for Next Generation Materials.

The inherent differences in reactivity between activated and non-activated alkenes prevents copolymerization using established polymer synthesis techniques. Research over the past 20 years has greatly advanced the copolymerization of polar vinyl monomers and olefins. This Review highlights the challenges associated with conventional polymerization systems and evaluates the most relevant methods which have been developed to "bridge the gap" between polar vinyl monomers and olefins. We discuss advancements in heteroatom tolerant coordination-insertion polymerizations, methods of controlling radical polymerizations to incorporate olefinic monomers, as well as combined approaches employing sequential polymerizations. Finally, we discuss state-of-the-art stimuli-responsive systems capable of facile switching between catalytic pathways and provide an outlook towards applications in which tailored copolymers are ideally suited.

Clinical trial registration and reporting: a survey of academic organizations in the United States.

BACKGROUND: Many clinical trials conducted by academic organizations are not published, or are not published completely. Following the US Food and Drug Administration Amendments Act of 2007, "The Final Rule" (compliance date April 18, 2017) and a National Institutes of Health policy clarified and expanded trial registration and results reporting requirements. We sought to identify policies, procedures, and resources to support trial registration and reporting at academic organizations. METHODS: We conducted an online survey from November 21, 2016 to March 1, 2017, before organizations were expected to comply with The Final Rule. We included active Protocol Registration and Results System (PRS) accounts classified by ClinicalTrials.gov as a "University/Organization" in the USA. PRS administrators manage information on ClinicalTrials.gov. We invited one PRS administrator to complete the survey for each organization account, which was the unit of analysis. RESULTS: Eligible organization accounts (N = 783) included 47,701 records (e.g., studies) in August 2016. Participating organizations (366/783; 47%) included 40,351/47,701 (85%) records. Compared with other organizations, Clinical and Translational Science Award (CTSA) holders, cancer centers, and large organizations were more likely to participate. A minority of accounts have a registration (156/366; 43%) or results reporting policy (129/366; 35%). Of those with policies, 15/156 (11%) and 49/156 (35%) reported that trials must be registered before institutional review board approval is granted or before beginning enrollment, respectively. Few organizations use computer software to monitor compliance (68/366; 19%). One organization had penalized an investigator for non-compliance. Among the 287/366 (78%) accounts reporting that they allocate staff to fulfill ClinicalTrials.gov registration and reporting requirements, the median number of full-time equivalent staff is 0.08 (interquartile range = 0.02-0.25). Because of non-response and social desirability, this could be a "best case" scenario. CONCLUSIONS: Before the compliance date for The Final Rule, some academic organizations had policies and resources that facilitate clinical trial registration and reporting. Most organizations appear to be unprepared to meet the new requirements. Organizations could enact the following: adopt policies that require trial registration and reporting, allocate resources (e.g., staff, software) to support registration and reporting, and ensure there are consequences for investigators who do not follow standards for clinical research.

Effects of 2% Dehydration on Lactate Concentration During Constant-Load Cycling.

Green, JM, Miller, B, Simpson, J, Dubroc, D, Keyes, A, Neal, K, Gann, J, and Andre, T. Effects of 2% dehydration on lactate concentration during constant-load cycling. J Strength Cond Res 32(7): 2066-2071, 2018-The lactate [La] threshold (LT) can predict endurance performance potential. Dehydration may alter LT. This study examined effects of dehydration on [La] response during constant-load cycling. Recreationally fit (V[Combining Dot Above]O2peak = 48.7 ± 5.2 ml·kg·min) male participants (n = 9) completed 2 × 40-minute constant-load cycling trials; euhydrated (HYD) and after previous evening passive (water bath) dehydration (2% body weight, DEH) (HYD and DEH counterbalanced). Lactate, heart rate (HR), 10-point Omni ratings of perceived exertion (RPE), and rectal temperature (Trec) were measured after warm-up (WU) and at 10, 20, 30, and 40 minutes. Before cycling, urine specific gravity (USG) was measured and participants estimated perceived recovery status (PRS). Urine specific gravity DEH (1.027 ± 0.004) was significantly greater than HYD (1.013 ± 0.007). After WU, [La] was significantly greater (all time points) for DEH (∼4.1 mmol·L) vs. HYD (∼3.5 mmol·L) with similar results for HR (DEH: ∼167, HYD: ∼158 b·min). For DEH, RPE was significantly greater (∼1 unit) at 20, 30, and 40 minutes, and Trec was significantly greater at 30 and 40 minutes (∼0.4° C). DEH (vs. HYD) also resulted in significantly different resting HR (93 ± 6, vs. 85 ± 7 b·min), significantly greater session RPE (7.7 ± 1.1 vs. 5.3 ± 1.1), and significantly lower subjective feelings of recovery (PRS = 6.4 ± 2.9, vs. 9.0 ± 1.5). Current results indicate systematic changes in [La] and associated physiological responses result from previous day dehydration. Hydration status should be a concern in paradigms where [La] assessment is used.

Recent progress on the development of anisotropic gold nanoparticles: Design strategies and growth mechanism.

This review summarizes recent advances on design strategies for shape-controlled anisotropic gold nanoparticles. Detailed chemical mechanism has been discussed to understand the anisotropic growth. The effect of various chemical parameters and surface facets for the formation of different shaped anisotropic nanoparticles have been addressed.

Tuning Sizes, Morphologies, and Magnetic Properties of Monocore Versus Multicore Iron Oxide Nanoparticles through the Controlled Addition of Water in the Polyol Synthesis.

The polyol route is a versatile and up-scalable method to produce large batches of iron oxide nanoparticles with well-defined structures and magnetic properties. Importance of parameters such as temperature and reaction time, heating profile, nature of the polyol solvent or organometallic precursors on nanostructure and properties has already been described in the literature. Yet, the crucial role of water in the forced hydrolysis pathway has never been reported, despite its mandatory presence for nanoparticle production. This communication investigates the influence of the water amount and temperature at which it is injected in the reflux system for either a pure polyol solvent system or a mixture with poly(hydroxy)amine. Distinct morphologies of nanoparticles were thereby obtained, from ultra-ultra-small smooth spheres down to 4 nm in diameter to larger ones up to 37 nm. Well-defined multicore assemblies with narrow grain size dispersity termed nanoflowers were also synthesized. A diverse and large library of samples was obtained by manipulating the nature of solvents and the amount of added water while keeping all other parameters constant. The different morphologies lead to magnetic nanoparticles suitable for important biomedical applications such as magnetic hyperthermia, magnetic resonance imaging (MRI) contrast agent, or both.

Creating a Program to Support Registering and Reporting Clinical Trials at Johns Hopkins University.

PROBLEM: The Food and Drug Administration Amendments Act of 2007 (FDAAA) and the National Institutes of Health (NIH) require that many clinical trials register and report results on ClinicalTrials.gov. Noncompliance with these policies denies research participants and scientists access to potentially relevant findings and could lead to monetary penalties or loss of funding. After discovering hundreds of potentially noncompliant trials affiliated with the institution, the Johns Hopkins University School of Medicine (JHUSOM) sought to develop a program to support research teams with registration and reporting requirements. APPROACH: JHUSOM conducted a baseline assessment of institutional compliance in 2015, launched the ClinicalTrials.gov Program in June 2016, and expanded the program to the Sidney Kimmel Comprehensive Cancer Center in April 2018. The program is innovative in its comprehensive approach, and it was among the first to bring a large number of trials into compliance. OUTCOMES: From September 2015 to September 2020, JHUSOM brought completed and ongoing trials into compliance with FDAAA and NIH policies and maintained almost perfect compliance for new trials. During this period, the proportion of trials potentially noncompliant with the FDAAA decreased from 44% (339/774) to 2% (32/1,304). NEXT STEPS: JHUSOM continues to develop and evaluate tools and procedures that facilitate trial registration and results reporting. In collaboration with other academic medical centers, JHUSOM plans to share resources and to identify and disseminate best practices. This report identifies practical lessons for institutions that might develop similar programs.