Photophysical Studies of a Zr(IV) Complex with Two Pyrrolide-Based Tetradentate Schiff Base Ligands.

The reaction of two equivalents of N,N'-bis(2-pyrrolylmethylidene)-1,2-phenylenediamine (H2bppda) with tetrabenzylzirconium provided the air- and moisture-stable eight-coordinate complex Zr(bppda)2. Temperature-dependent steady-state and time-resolved emission spectroscopy established weak photoluminescence (ΦPL = 0.4% at 293 K) by a combination of prompt fluorescence and thermally activated delayed fluorescence (TADF) upon visible light excitation at and around room temperature. TADF emission is strongly quenched by 3O2 and shows highly temperature-sensitive emission lifetimes of hundreds of microseconds. The lifetime of the lowest energy singlet excited state, S1, was established by transient absorption spectroscopy and shows rapid deactivation (τ = 142 ps) by prompt fluorescence and intersystem crossing to the triplet state, T1. Time-dependent density functional theory (TD-DFT) calculations predict moderate ligand-to-metal charge transfer (LMCT) contributions of 25-30% for the S1 and T1 states. A comparison of Zr(bppda)2 to related zirconium pyridine dipyrrolide complexes, Zr(PDP)2, revealed important electronic structure changes due to the eight-coordinate ligand environment in Zr(bppda)2, which were correlated to differences in the photophysical properties between the two compound classes.

A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P < 0.05) in the joint meta-analysis with the HGI (Ncases = 44,820; Ncontrols = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.

Genomics-informed delineation of conservation units in a desert amphibian.

Delineating conservation units (CUs, e.g., evolutionarily significant units, ESUs, and management units, MUs) is critical to the recovery of declining species because CUs inform both listing status and management actions. Genomic data have strengths and limitations in informing CU delineation and related management questions in natural systems. We illustrate the value of using genomic data in combination with landscape, dispersal and occupancy data to inform CU delineation in Nevada populations of the Great Basin Distinct Population Segment of the Columbia spotted frog (Rana luteiventris). R. luteiventris occupies naturally fragmented aquatic habitats in this xeric region, but beaver removal, climate change and other factors have put many of these populations at high risk of extirpation without management intervention. We addressed three objectives: (i) assessing support for ESUs within Nevada; (ii) evaluating and revising, if warranted, the current delineation of MUs; and (iii) evaluating genetic diversity, effective population size, adaptive differentiation and functional connectivity to inform ongoing management actions. We found little support for ESUs within Nevada but did identify potential revisions to MUs based on unique landscape drivers of connectivity that distinguish these desert populations from those in the northern portion of the species range. Effective sizes were uniformly small, with low genetic diversity and weak signatures of adaptive differentiation. Our findings suggest that management actions, including translocations and genetic rescue, might be warranted. Our study illustrates how a carefully planned genetic study, designed to address priority management goals that include CU delineation, can provide multiple insights to inform conservation action.

Long-Lived Photoluminescence of Molecular Group 14 Compounds through Thermally Activated Delayed Fluorescence.

Photoluminescent molecules exploiting the sizable spin-orbit coupling constants of main group metals and metalloids to access long-lived triplet excited states are relatively rare compared to phosphorescent transition metal complexes. Here we report the synthesis of three air- and moisture-stable group 14 compounds E(MePDPPh)2, where E = Si, Ge, or Sn and [MePDPPh]2- is the doubly deprotonated form of 2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2-yl)pyridine. In solution, all three molecules exhibit exceptionally long-lived triplet excited states with lifetimes in the millisecond range and show highly efficient photoluminescence (Φ ≤ 0.49) due to competing prompt fluorescence and thermally activated delayed fluorescence at and around room temperature. Temperature-dependent steady-state emission spectra and photoluminescent lifetime measurements provided conclusive evidence for the two distinct emission pathways. Picosecond transient absorption spectroscopy allowed further analysis of the intersystem crossing (ISC) between singlet and triplet manifolds (τISC = 0.25-3.1 ns) and confirmed the expected trend of increased ISC rates for the heavier elements in otherwise isostructural compounds.

A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD.

BACKGROUND: Exposure to high doses or a high cumulative dose of erythropoiesis-stimulating agents (ESAs) may contribute to cardiovascular events in patients with CKD and anemia. Whether using a low fixed ESA dose versus dosing based on a hemoglobin-based, titration-dose algorithm in such patients might reduce risks associated with high ESA doses and decrease the cumulative exposure-while reducing the need for red blood cell transfusions-is unknown. METHODS: In this phase-3, randomized trial involving 756 adults with stage-3 to -5 CKD and anemia, we evaluated incidence of red blood cell transfusions for participants randomized to receive darbepoetin given as a fixed dose (0.45 µg/kg every 4 weeks) versus administered according to a hemoglobin-based, titration-dose algorithm, for up to 2 years. Participants received transfusions as deemed necessary by the treating physician. RESULTS: There were 379 patients randomized to the fixed-dose group, and 377 to the titration-dose group. The percentage of participants transfused did not differ (24.1% and 24.4% for the fixed-dose and titration-dose group, respectively), with similar time to first transfusion. The titration-dose group achieved significantly higher median hemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl). The fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 µg) compared with the titration-dose group (53.6 µg median monthly dose). The FD and TD group received a median (Q1, Q3) cumulative dose per 4 weeks of darbepoetin of 30.9 (21.8, 40.0) µg and 53.6 (31.1, 89.9) µg, respectively; the median of the difference between treatment groups was -22.1 (95% CI, -26.1 to -18.1) µg. CONCLUSIONS: These findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing.

High Magnetic Anisotropy of a Square-Planar Iron-Carbene Complex.

Among Earth-abundant catalyst systems, iron-carbene intermediates that perform C-C bond forming reactions such as cyclopropanation of olefins and C-H functionalization via carbene insertion are rare. Detailed descriptions of the possible electronic structures for iron-carbene bonds are imperative to obtain better mechanistic insights and enable rational catalyst design. Here, we report the first square-planar iron-carbene complex (MesPDPPh)Fe(CPh2), where [MesPDPPh]2- is the doubly deprotonated form of [2,6-bis(5-(2,4,6-trimethylphenyl)-3-phenyl-1H-pyrrol-2-yl)pyridine]. The compound was prepared via reaction of the disubstituted diazoalkane N2CPh2 with (MesPDPPh)Fe(thf) and represents a rare example of a structurally characterized, paramagnetic iron-carbene complex. Temperature-dependent magnetic susceptibility measurements and applied-field Mössbauer spectroscopic studies revealed an orbitally near-degenerate S = 1 ground state with large unquenched orbital angular momentum resulting in high magnetic anisotropy. Spin-Hamiltonian analysis indicated that this S = 1 spin system has uniaxial magnetic properties arising from a ground MS = ±1 non-Kramers doublet that is well-separated from the MS = 0 sublevel due to very large axial zero-field splitting (D = -195 cm-1, E/D = 0.02 estimated from magnetic susceptibility data). This remarkable electronic structure gives rise to a very large, positive magnetic hyperfine field of more than +60 T for the 57Fe nucleus along the easy magnetization axis observed by Mössbauer spectroscopy. Computational analysis with complete active space self-consistent field (CASSCF) calculations provides a detailed electronic structure analysis and confirms that (MesPDPPh)Fe(CPh2) exhibits a multiconfigurational ground state. The majority contribution originates from a configuration best described as a singlet carbene coordinated to an intermediate-spin FeII center with a (dxy)2{(dxz),(dz2)}3(dyz)1(dx2-y2)0 configuration featuring near-degenerate dxz and dz2 orbitals.

Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis.

BACKGROUND: Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. METHODS: We enrolled 4093 postmenopausal women with osteoporosis and a fragility fracture and randomly assigned them in a 1:1 ratio to receive monthly subcutaneous romosozumab (210 mg) or weekly oral alendronate (70 mg) in a blinded fashion for 12 months, followed by open-label alendronate in both groups. The primary end points were the cumulative incidence of new vertebral fracture at 24 months and the cumulative incidence of clinical fracture (nonvertebral and symptomatic vertebral fracture) at the time of the primary analysis (after clinical fractures had been confirmed in ≥330 patients). Secondary end points included the incidences of nonvertebral and hip fracture at the time of the primary analysis. Serious cardiovascular adverse events, osteonecrosis of the jaw, and atypical femoral fractures were adjudicated. RESULTS: Over a period of 24 months, a 48% lower risk of new vertebral fractures was observed in the romosozumab-to-alendronate group (6.2% [127 of 2046 patients]) than in the alendronate-to-alendronate group (11.9% [243 of 2047 patients]) (P<0.001). Clinical fractures occurred in 198 of 2046 patients (9.7%) in the romosozumab-to-alendronate group versus 266 of 2047 patients (13.0%) in the alendronate-to-alendronate group, representing a 27% lower risk with romosozumab (P<0.001). The risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients [8.7%] vs. 217 of 2047 patients [10.6%]; P=0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients [2.0%] vs. 66 of 2047 patients [3.2%]; P=0.02). Overall adverse events and serious adverse events were balanced between the two groups. During year 1, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (50 of 2040 patients [2.5%] vs. 38 of 2014 patients [1.9%]). During the open-label alendronate period, adjudicated events of osteonecrosis of the jaw (1 event each in the romosozumab-to-alendronate and alendronate-to-alendronate groups) and atypical femoral fracture (2 events and 4 events, respectively) were observed. CONCLUSIONS: In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone. (Funded by Amgen and others; ARCH ClinicalTrials.gov number, NCT01631214 .).

Effects of Ligand Substitution on the Optical and Electrochemical Properties of (Pyridinedipyrrolide)zirconium Photosensitizers.

A series of seven bis(pyridinedipyrrolide)zirconium complexes, Zr(R1PDPR2)2, where [R1PDPR2]2- is the doubly deprotonated form of [2,6-bis(5-R1-3-R2-1H-pyrrol-2-yl)pyridine], were prepared and characterized in solution by NMR, UV/vis absorption, and emission spectroscopy and cyclic voltammetry. The molecular structures were determined by single-crystal X-ray crystallography. All complexes exhibit remarkably long emission lifetimes (τ = 190-576 µs) with high quantum efficiencies (ΦPL = 0.10-0.38) upon excitation with visible light in a benzene solution. The substituents on the pyrrolide rings were shown to have significant effects on the photoluminescence and electrochemical properties of these compounds. The R2 substituents (R2 = H, Me, Ph, or C6F5) show only limited effects on the absorption and emission profiles of the complexes but allow systematic tuning of the ground- and excited-state redox potentials over a range of almost 600 mV. The R1 substituents (R1 = H, Me, Ph, or 2,4,6-Me3Ph) influence both the optical and electrochemical properties through electronic effects. Additionally, the R1 substituents have profound consequences for the structural flexibility and overall stability of the compounds. Distortions of the Zr(PDP)2 core from idealized D2d symmetry in the solid state can be traced to the steric profiles of the R1 substituents and correlate with the observed Stokes shifts for each compound. The complex with the smallest ligand system, Zr(HPDPH)2, coordinates two additional solvent molecules in a tetrahydrofuran (THF) solution, which allowed the isolation of photoluminescent, eight-coordinate Zr(HPDPH)2(THF)2. The photoredox catalytic dehalogenation of aryl iodides and aryl chlorides using the most reducing derivative, Zr(MePDPMe)2, highlights the potential of Zr(PDP)2 photosensitizers to promote challenging reductive transformations under mild conditions upon excitation with green light.

A Fraction of Recommended Practices: Implementation of the FIFA 11+ in NCAA Soccer Programs.

Background and Objectives: National Collegiate Athletic Association (NCAA) soccer coaches implement numerous warm-up and flexibility strategies to prepare athletes for training and competition. The Fédération Internationale de Football Association (FIFA) developed the 11+ injury prevention program to reduce non-contact injuries. This study aimed to analyze the level of familiarity with and implementation of the evidence-based FIFA 11+ amongst NCAA Division I (DI) and Division III (DIII) men's and women's soccer coaches. Materials and Methods: NCAA soccer coaches in the United States received an Institutional Review Board-approved survey hyperlink. A total of 240 coaches completed the survey. The respondents represented 47.5% men's and 52.5% women's teams distributed within DI and DIII programs. Descriptive statistics are reported as frequency counts and mean ± standard deviation where applicable. Pearson's chi-square tests were performed to assess potential differences with a significance level set at α < 0.05. Results: The results indicated that approximately 62% of the respondents reported being familiar with the FIFA 11+ program. Of those coaches familiar with the program, 15.0% reported full implementation, 57.5% reported partial implementation, and 27.5% reported no implementation. Chi-square analyses revealed significant differences in FIFA 11+ implementation based upon division level (χ2 = 4.56, p = 0.033) and coaching certification levels (χ2 = 13.11, p = 0.011). Conclusions: This study indicates that there is a gap between FIFA 11+ knowledge and actual implementation. To reduce the risk of non-contact injury, there is a need to educate coaches and athletic trainers on the purpose of the FIFA 11+ program and how to perform the exercises correctly.

Photoluminescence of Seven-Coordinate Zirconium and Hafnium Complexes with 2,2'-Pyridylpyrrolide Ligands.

Luminescent seven-coordinated zirconium and hafnium complexes bearing three mono-anionic 2,2'-pyridylpyrrolide ligands and one chloride were synthesized. Solid-state structures and the dynamic behaviors in solution were probed by X-ray crystallography and variable temperature 1 H NMR experiments, respectively. Absorption spectroscopy and time-dependent density functional theory (TD-DFT) calculations supported a hybrid of ligand-to-metal charge transfer (LMCT)/ligand-to-ligand charge transfer (LLCT) for the visible light absorption band. The complexes (Me PMPMe )3 MCl (M=Zr, Hf, Me PMPMe =3,5-dimethyl-2-(2-pyridyl)pyrrolide) are emissive in solution at room temperature upon irradiation with visible light due to a combination of phosphorescence and fluorescence characterized by excited state lifetimes in the µs and low to sub-ns timescale, respectively. Electrochemical experiments revealed that the zirconium complex possesses a reversible redox event under highly reducing condition (-2.29 V vs. Fc+/0 ).

Reactivity of Pyridine Dipyrrolide Iron(II) Complexes with Organic Azides: C-H Amination and Iron Tetrazene Formation.

Reaction of (MesPDPPh)Fe(thf) (H2MesPDPPh = 2,6-bis(5-(2,4,6-trimethylphenyl)-3-phenyl-1H-pyrrol-2-yl)pyridine) with organic azides has been studied. The identity of the azide substituent had a profound impact on the transformation type and nature of the observed products. Reaction with aromatic p-tolyl azide, N3Tol, resulted in exclusive formation of the corresponding iron tetrazene complex (MesPDPPh)Fe(N4Tol2). In contrast, the use of bulky 1-adamantyl azide led to clean intramolecular C-H amination of one of the benzylic C-H bonds of a mesityl substituent on the pyridine dipyrrolide, PDP, supporting ligand. The smaller aliphatic substituent in benzyl azide allowed for the isolation of two different compounds from distinct reaction pathways. One product is the result of double C-H amination of the PDP ligand via nitrene transfer, while the second one contains a dibenzyltetrazene and a benzaldimine ligand. All isolated complexes were characterized using a combination of X-ray crystallography, solid state magnetic susceptibility measurements, 1H NMR and 57Fe Mössbauer spectroscopy, and density functional theory (DFT), and their electronic structures were elucidated. Potential electronic structures for putative iron(IV) imido or iron(III) imidyl radical complexes were explored via DFT calculations.

Synthesis and Electronic Structure of Neutral Square-Planar High-Spin Iron(II) Complexes Supported by a Dianionic Pincer Ligand.

Two square-planar high-spin FeII complexes bearing a dianionic pyridine dipyrrolate pincer ligand and a diethyl ether or tetrahydrofuran ligand were synthesized and structurally characterized, and their electronic structures were elucidated by a combined spectroscopic and computational approach. In contrast to previous examples, the S = 2 ground states of these square-planar FeII complexes do not require an overall anionic charge of the compounds or incorporation of alkali metal cations. The tetrahydrofuran complex exhibits an equilibrium between four- and five-coordinate species in solution, which was supported by 1H NMR and 57Fe Mössbauer spectroscopy and comparison to a structurally characterized five-coordinate pyridine dipyrrolate iron bis-pyridine adduct. A detailed computational analysis of the electronic structures of the four- and five-coordinate species via density functional theory provides insight into the origins of the unusual ground state configurations for FeII in a square-planar ligand field and explains the associated characteristic spectroscopic parameters.

A Zirconium Photosensitizer with a Long-Lived Excited State: Mechanistic Insight into Photoinduced Single-Electron Transfer.

Time-resolved emission spectroscopy for the luminescent zirconium complex Zr(MePDP)2 (MePDP = 2,6-bis(5-methyl-3-phenyl-1 H-pyrrol-2-yl)pyridine) revealed a long-lived excited state with a lifetime τ = 325 ± 10 µs. Computational studies using time-dependent density functional theory were conducted to identify the nature of the luminescent excited state as a mixed triplet intraligand/ligand-to-metal charge-transfer state. Stern-Volmer experiments showed a strong dependence of the quenching rate on the redox potential of the quencher indicating photoinduced single-electron transfer (SET) as the quenching pathway. Mechanistic investigations of the photocatalytic homocoupling of benzyl bromide allowed the detection of organic radical intermediates during turnover and provided further evidence for SET mediated by Zr(MePDP)2. Isolation of the one-electron-reduced form of the photosensitizer, [Zr(MePDP)2]-, enabled studies of its electronic structure by a combination of experimental and computational techniques and confirmed its role as a strong reductant. Additionally, the role of the benzimidazolium hydride derivatives as two-electron sacrificial reductants during photoredox catalysis was investigated. In combination, the results presented in this report establish a detailed mechanistic picture of a photoredox catalytic reaction promoted by an earth-abundant early transition metal photosensitizer.

Synthesis of a Cyclophane Bearing Two Benz[a]anthracene Units Connected at the 5 and 7 Positions with Two Naphth-1,4-diyl Groups.

A synthetic pathway to a cyclophane bearing two benz[a]anthracene units connected at the 5 and 7 positions through two naphth-1,4-diyl groups was developed, and its structure was confirmed by X-ray structure analysis. Because of structural constraints, the two naphthyl groups are distorted from planarity and the bonds connecting them to the benz[a]anthracene units are bent significantly. The UV-vis and fluorescence spectra of the cyclophane are red-shifted from those of 7-(1-naphthalenyl)benz[a]anthracene, which is the corresponding monomeric polycyclic aromatic hydrocarbon.

Redox Chemistry of Bis(pyrrolyl)pyridine Chromium and Molybdenum Complexes: An Experimental and Density Functional Theoretical Study.

The three- and four-membered redox series [Cr(MePDP)2]z (z = 1-, 2-, 3-) and [Mo(MePDP)2]z (z = 0, 1-, 2-, 3-) were synthesized to study the redox properties of the pincer ligand MePDP2- (H2MePDP = 2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2-yl)pyridine). The monoanionic complexes were characterized by X-ray crystallography, UV/vis/NIR spectroscopy, and magnetic susceptibility measurements. Experimental and density functional theory (DFT) studies are consistent with closed-shell MePDP2- ligands and +III oxidation states (d3, S = 3/2) for the central metal ions. Cyclic voltammetry established multiple reversible redox processes for [M(MePDP)2]1- (M = Cr, Mo), which were further investigated via chemical oxidation and reduction. For molybdenum, one-electron oxidation yielded Mo(MePDP)2 which was characterized by X-ray crystallography, UV/vis/NIR, and magnetic susceptibility measurements. The experimental and computational data indicate metal-centered oxidation to a MoIV complex (d2, S = 1) with two MePDP2- ligands. In contrast, one- and two-electron reductions were found to be ligand centered resulting in the formation of MePDP•3- radicals, in which the unpaired electron is predominantly located on the central pyridine ring of the ligand. The presence of ligand radicals was established experimentally by observation of ligand-to-ligand intervalence charge transfer (LLIVCT) bands in the UV/vis/NIR spectra of the dianionic and trianionic complexes and further supported by broken-symmetry DFT calculations. X-ray crystallographic analyses of the one-electron-reduced species [M(MePDP)2]2- (S = 1, M = Cr, Mo) established structural indicators for pincer reduction and showed localization of the radical on one of the two pincer ligands. The two-electron-reduced, trianionic complexes (S = 1/2) were characterized by UV/vis/NIR spectroscopy, magnetic susceptibility measurements, and EPR spectroscopy. The electronic structures of the reduced complexes are best described as containing +III metal ions (d3) antiferromagnetically coupled to one and two radical ligands for the dianionic and trianionic species, respectively.

De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease.

BACKGROUND: Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. METHODS: One-hundred sixteen pediatric ESA-naïve subjects (aged 1-18 years) with CKD stages 3-5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2 years. RESULTS: In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0-12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases. CONCLUSIONS: Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl.

Synthesis of Partially Hydrogenated Cycloparaphenylenes with Bent and Fused Structures Bearing Armchair Carbon Nanotube-like Connections.

The Diels-Alder reactions between 2 equiv of (E,E)-1,4-bis(4-bromophenyl)-1,3-butadiene and 1,4-benzoquinone led to the formation of a key intermediate with all four 4-bromophenyl substituents cis to one another. The subsequent nickel-mediated homocoupling reactions then produced partially hydrogenated cycloparaphenylenes, including a molecule bearing two units of tetrahydro[6]cycloparaphenylene (4H[6]CPP) fused together through two 1,4-dimethoxybenzene units in an armchair (6,6)carbon nanotube-like connection. Similarly, two 6H[9]CPPs were connected through three 1,4-dimethoxybenzene units in an armchair (9,9)carbon nanotube-like arrangement. A bent 8H[12]CPP and a bent 12H[18]CPP, which were fused intramolecularly with two and three 1,4-dimethoxybenzene units, respectively, to create the bent structures, were likewise synthesized. A molecule containing a bent 8H[12]CPP fused to a 4H[6]CPP was likewise constructed. The structures of these partially hydrogenated CPPs were established by X-ray structure analysis, NMR spectroscopy, and additional independent synthetic pathways.

Synthesis and Characterization of Functionalized [12]Cycloparaphenylenes Containing Four Alternating Biphenyl and Naphthyl Units.

Functionalized [12]cycloparaphenylenes ([12]CPPs) containing four alternating biphenyl and naphthyl units were synthesized. A macrocyclic furan-containing CPP precursor was used for the Diels-Alder reaction with the parent benzyne or 3,6-dimethoxybenzyne to form the corresponding macrocyclic carbon frameworks. The subsequent reductive deoxygenation of the Diels-Alder adducts with Fe2(CO)9 followed by oxidative aromatization with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone produced the functionalized [12]CPPs. The effect of macrocyclic ring size on the reaction rate of oxidative aromatization was investigated.

Neoplasms of the Appendix: Pictorial Review with Clinical and Pathologic Correlation.

Appendiceal neoplasms are uncommon tumors of the gastrointestinal tract that may manifest with symptoms of appendicitis, right lower quadrant pain, or palpable mass, leading to imaging or surgical intervention. The majority of appendiceal masses consist of primary epithelial neoplasms and neuroendocrine tumors (NETs). Epithelial neoplasms-mucinous and nonmucinous types-are more often detected at imaging than NETs due to their larger size and propensity for peritoneal spread and metastatic disease. Epithelial mucinous neoplasms are defined by the presence of mucin, detected at radiologic and pathologic examination. A mucocele or pseudomyxoma peritonei from epithelial mucinous tumors are the two most common cross-sectional imaging findings of appendiceal mucinous neoplasms. Nonmucinous epithelial tumors are less common and manifest as masses similar to colonic-type malignancies. NETs are often discovered incidentally at appendectomy due to their small size and nonaggressive behavior. Imaging findings of primary appendiceal tumors may overlap with those of acute appendicitis. Additionally, an appendiceal mass may cause acute appendicitis, obscuring the underlying mass. Other neoplasms including lymphoma, sarcoma, mesenchymal and nerve sheath tumors, or secondary malignant involvement of the appendix are rare. Treatment depends on the histologic subtype and extent of disease. Detailed description of organ, nodal, and peritoneal involvement informs surgical management with the goal of complete cytoreduction. Novel treatments such as hyperthermic intraperitoneal chemotherapy have increased survival for patients with mucinous tumors. ©RSNA, 2017.

A Luminescent Zirconium(IV) Complex as a Molecular Photosensitizer for Visible Light Photoredox Catalysis.

Titanium and zirconium complexes carrying two 2,6-bis(pyrrolyl)pyridine ligands have been synthesized and characterized. The neutral complexes Ti(MePDP)2 and Zr(MePDP)2 (MePDP = 2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2-yl)pyridine) show intense ligand-to-metal charge-transfer bands in the visible region and undergo multiple reversible redox events under highly reducing conditions. Zr(MePDP)2 exhibits photoluminescent behavior and its excited state can be quenched by mild reductants to generate a powerful electron transfer reagent with a ground state potential of -2.16 V vs Fc+/0. This reactivity was utilized to facilitate dehalogenation reactions, the reduction of electron-poor olefins, and the reductive coupling of benzyl bromide via photoredox catalysis. In these reactions, the earth-abundant metal complex Zr(MePDP)2 acts as a substitute for the precious metal photosensitizer [Ru(bpy)3]2+.