Synthesis, characterisation and reactivity of a zinc triazenide for potential use in vapour deposition.

In this study, we synthesised and characterised a new zinc(II) triazenide for potential use in vapour deposition of zinc sulphide thin films. The compound is volatile and quantitatively sublimes at 80 °C under vacuum (0.5 mbar). Thermogravimetric analysis showed a one-step volatilisation with an onset temperature at ∼125 °C and 5% residual mass. The compound also reacted with 2 or 4 molar equivalents of triphenylsilanethiol to give dimeric and monomeric zinc thiolates, respectively. The high volatility, thermal stability, and reactivity with sterically hindered thiols makes this compound a potential candidate for use in vapour deposition of zinc containing thin films.

Synthesis, Structure, and Thermal Properties of Volatile Group 11 Triazenides as Potential Precursors for Vapor Deposition.

Group 11 thin films are desirable as interconnects in microelectronics. Although many M-N-bonded Cu precursors have been explored for vapor deposition, there is currently a lack of suitable Ag and Au derivatives. Herein, we present monovalent Cu, Ag, and Au 1,3-di-tert-butyltriazenides that have potential for use in vapor deposition. Their thermal stability and volatility rival that of current state-of-the-art group 11 precursors with bidentate M-N-bonded ligands. Solution-state thermolysis of these triazenides yielded polycrystalline films of elemental Cu, Ag, and Au. The compounds are therefore highly promising as single-source precursors for vapor deposition of coinage metal films.

Thermal atomic layer deposition of In2O3 thin films using a homoleptic indium triazenide precursor and water.

Indium oxide (In2O3) is an important transparent conducting material widely used in optoelectronic applications. Herein, we study the deposition of In2O3 by thermal atomic layer deposition (ALD) using our recently reported indium(III) triazenide precursor and H2O. A temperature interval with self-limiting growth was found between ∼270 and 385 °C with a growth per cycle of ∼1.0 Å. The deposited films were polycrystalline cubic In2O3 with In : O ratios of 1 : 1.2, and low levels of C and no detectable N impurities. The transmittance of the films was found to be >70% in visible light and the resistivity was found to be 0.2 mΩ cm. The high growth rates, low impurities, high optical transmittance, and low resistivity of these films give promise to this process being used for ALD of In2O3 films for future microelectronic displays.

Synthesis and structure of a phosphinoboronic ester in a fused bicyclic framework.

The first phosphinoboronic ester bearing a fused bicyclic framework was synthesised by either deprotonation and hydride abstraction or Rh-catalysed dehydrogenation of a hydrophosphineboronic ester. The phosphinoboronic ester reacted as a Lewis acid with KF/18-crown-6, pyridine and DMAP to give the corresponding adducts. Furthermore, its crystal structure shows a remarkably short P-B bond in comparison with other P-B bonded derivatives in spite of the trigonal pyramidal geometry of the phosphorus. Consistent with the phosphorus pyramidality, the π-type donor-acceptor interaction of the P-B bond is small as revealed by the DFT calculations. The P-B bond shared within the fused six-membered rings has to shorten because of the geometrical requirement and high s-character of the boron.

Assessing Self-Efficacy and Communication Regarding Sexual Agreements among Men Who Have Sex with Men in the USA: Development and Validation of Two Novel Scales.

HIV disproportionately impacts men who have sex with men (MSM) in the USA. Building upon research on relationship constructs unique to MSM couples' HIV-prevention needs, we developed two new scales measuring sexual agreement self-efficacy (SASE) and importance of sexual agreement communication (ISAC). Following qualitative item development, we used two large independent samples of MSM couples (N1 = 441, N2 = 388) to conduct scale validation. Exploratory factor analyses indicated both SASE and ISAC to be unidimensional with 7 and 5 items (eigenvalues = 5.68 and 3.50), respectively, with strong factor loadings. Confirmatory factor analyses yielded satisfactory model fit for SASE (CFI = 0.99; SRMR = 0.03) and ISAC (CFI = 0.99; SRMR = 0.05). Reliability was high for SASE (ω = 0.92) and ISAC (ω = 0.84). Predictive validity analysis revealed a protective association between higher scores on both scales and the outcomes of sexual risk behavior and agreement breaks. Convergent and discriminant validity analyses demonstrated associations in the expected directions between these scales and multiple measures of relationship quality. Therefore, SASE and ISAC are two brief, valid, and reliable scales that can facilitate more in-depth explorations of sexual agreements in MSM and thereby contribute greatly to improving our understanding of and ability to intervene on sexual agreements to improve health and relationship outcomes.

Synthesis, Characterization, and Thermal Study of Divalent Germanium, Tin, and Lead Triazenides as Potential Vapor Deposition Precursors.

Only a few M-N bonded divalent group 14 precursors are available for vapor deposition, in particular for Ge and Pb. A majority of the reported precursors are dicoordinated with the Sn(II) amidinates, the only tetracoordinated examples. No Ge(II) and Pb(II) amidinates suitable for vapor deposition have been demonstrated. Herein, we present tetracoordinated Ge(II), Sn(II), and Pb(II) complexes bearing two sets of chelating 1,3-di-tert-butyltriazenide ligands. These compounds are thermally stable, sublime quantitatively between 60 and 75 °C (at 0.5 mbar), and show ideal single-step volatilization by thermogravimetric analysis.

Resolving Impurities in Atomic Layer Deposited Aluminum Nitride through Low Cost, High Efficiency Precursor Design.

A heteroleptic amidoalane precursor is presented as a more suitably designed candidate to replace trimethylaluminum (TMA) for atomic layer deposition of aluminum nitride (AlN). The lack of C-Al bonds and the strongly reducing hydride ligands in [AlH2(NMe2)]3 (1) were specifically chosen to limit impurities in target aluminum nitride (AlN) films. Compound 1 is made in a high yield, scalable synthesis involving lithium aluminum hydride and dimethylammonium chloride. It has a vapor pressure of 1 Torr at 40 °C and evaporates with negligible residual mass in thermogravimetric experiments. Ammonia (NH3) plasma and 1 in an atomic layer deposition (ALD) process produced crystalline AlN films above 200 °C with an Al:N ratio of 1.04. Carbon and oxygen impurities in resultant AlN films were reduced to <1% and <2%, respectively. By using a precursor with a rational and advantageous design, we can improve the material quality of AlN films compared to those deposited using the industrial standard trimethylaluminum and could reduce material cost by up to 2 orders of magnitude.

Synthesis and Thermal Study of Hexacoordinated Aluminum(III) Triazenides for Use in Atomic Layer Deposition.

Amidinate and guanidinate ligands have been used extensively to produce volatile and thermally stable precursors for atomic layer deposition. The triazenide ligand is relatively unexplored as an alternative ligand system. Herein, we present six new Al(III) complexes bearing three sets of a 1,3-dialkyltriazenide ligand. These complexes volatilize quantitatively in a single step with onset volatilization temperatures of ∼150 °C and 1 Torr vapor pressures of ∼134 °C. Differential scanning calorimetry revealed that these Al(III) complexes exhibited exothermic events that overlapped with the temperatures of their mass loss events in thermogravimetric analysis. Using quantum chemical density functional theory computations, we found a decomposition pathway that transforms the relatively large hexacoordinated Al(III) precursor into a smaller dicoordinated complex. The pathway relies on previously unexplored interligand proton migrations. These new Al(III) triazenides provide a series of alternative precursors with unique thermal properties that could be highly advantageous for vapor deposition processes of Al containing materials.

Predictors of cognitive behavioral therapy outcomes for insomnia in veterans with post-traumatic stress disorder.

BACKGROUND: Insomnia is a well-recognized co-morbid condition in veterans with post-traumatic stress disorder (PTSD) with negative personal and social consequences. Cognitive behavioral therapy (CBT) is considered an efficacious treatment, yet little attention has been devoted to treatment response in this population. The aim of this study was to identify factors that may predict clinical response to CBT for insomnia (CBT-I) in veterans with PTSD. METHODS: A retrospective chart review of 136 veterans with PTSD-related insomnia was conducted. Epworth Sleepiness Score (ESS), PTSD Checklist (PCL), and Insomnia Severity Index (ISI) were assessed at baseline. We converted prescribed antidepressant and hypnotic dosages before and after CBT-I to dose equivalent of fluoxetine diazepam, respectively. A 6-point reduction or greater in ISI scores at 6-month follow-up visit was defined as CBT-I responsiveness. RESULTS: CBT-I responsiveness was observed in 47% of veterans with PTSD. Seventy-seven percent completed treatment. Lack of perceived benefit was the most given reason for failure to return for follow-up. In contrast to hypnotics, antidepressants usage decreased in those who had experienced benefit from CBT-I (p = 0.001). Younger age, non-white race, and use of hypnotics prior to behavioral therapy were independently associated with lack of response to CBT-I. CONCLUSIONS: While CBT-I ameliorates insomnia in veterans with PTSD, the use of hypnotics prior to instituting behavioral therapy may negatively affect the response rate to CBT-I. Future studies should examine whether racial and cultural influences on the generation of insomnia in veterans with PTSD affects the response to CBT-I.

Trihydroborates and Dihydroboranes Bearing a Pentacoordinated Phosphorus Atom: Double Ring Expansion To Balance the Coordination States.

The first trihydroborate bearing a pentacoordinated phosphorus atom was synthesized as a new P-B bonded compound. Hydride abstraction of the trihydroborate gave an intermediary dihydroborane, which showed hydroboration reactivity and was trapped with pyridine whilst maintaining the P-B bond. The dihydroborane underwent a rearrangement, which involved a double ring expansion to compensate for the unbalanced coordination states of the phosphorus and boron atoms, to give a new fused bicyclic phosphine-boronate.

The synthesis and structure of a dianionic species with a bond between pentacoordinated tin atoms: bonding properties of the tin-tin bond.

The first dianionic compound bearing a bond between two pentacoordinated tin atoms, a distannate, was synthesized in a stable form by using two sets of an electron-withdrawing C,O-bidentate ligand on each tin atom. The structure of the distannate was determined by NMR spectroscopy and X-ray crystallographic analysis. The Sn-Sn bond of the distannate was shown to be a single bond featuring high s-character. The 1J(Sn-Sn) coupling constant was larger than that of Sn(sp3)-Sn(sp3) bonds found in most hexaorganodistannanes. This bond feature was also supported by computational studies. The Sn-Sn bond was cleaved by treatment with hydrochloric acid, which shows a different reactivity to the homonuclear bonds of pentacoordinated disilicates and digermanates.

Antimalarial activity of novel 4-cyano-3-methylisoquinoline inhibitors against Plasmodium falciparum: design, synthesis and biological evaluation.

Central to malaria pathogenesis is the invasion of human red blood cells by Plasmodium falciparum parasites. Following each cycle of intracellular development and replication, parasites activate a cellular program to egress from their current host cell and invade a new one. The orchestration of this process critically relies upon numerous organised phospho-signaling cascades, which are mediated by a number of central kinases. Parasite kinases are emerging as novel antimalarial targets as they have diverged sufficiently from their mammalian counterparts to allow selectable therapeutic action. Parasite protein kinase A (PfPKA) is highly expressed late in the cell cycle of the parasite blood stage and has been shown to phosphorylate a critical invasion protein, Apical Membrane Antigen 1. This enzyme could therefore be a valuable drug target so we have repurposed a substituted 4-cyano-3-methylisoquinoline that has been shown to inhibit rat PKA with the goal of targeting PfPKA. We synthesised a novel series of compounds and, although many potently inhibit the growth of chloroquine sensitive and resistant strains of P. falciparum, they were found to have minimal activity against PfPKA, indicating that they likely have another target important to parasite cytokinesis and invasion.

Synthesis and biological evaluation of 2-anilino-4-substituted-7H-pyrrolopyrimidines as PDK1 inhibitors.

PDK1, a biological target that has attracted a large amount of attention recently, is responsible for the positive regulation of the PI3K/Akt pathway that is often activated in a large number of human cancers. A series of second-generation 2-anilino-4-substituted-7H-pyrrolopyrimidines were synthesised by installation of various functions at the 4-position of the 7H-pyrrolopyrimidine scaffold. All compounds were screened against the isolated PDK1 enzyme and dose response analysis was obtained on the best compounds of the series.

Synthesis and biological evaluation of substituted 3-anilino-quinolin-2(1H)-ones as PDK1 inhibitors.

PDK1 is an important regulator of the PI3K/Akt pathway, which has been found frequently activated in a large number of human cancers. Herein we described the preparation of novel substituted 3-anilino-quinolin-2(1H)-ones as PDK1 inhibitors. The synthesis is based around a Buchwald-Hartwig cross-coupling of various 3-bromo-6-substituted-quinolin-2(1H)-ones with three different functionalised anilines. The modular nature of the designed synthesis allowed access to a series of novel inhibitors through derivatisation of a late-stage intermediate. All compounds were screened against isolated PDK1 enzyme, with modest inhibition observed.

Automatic scoring of medical students' clinical notes to monitor learning in the workplace.

BACKGROUND: Educators need efficient and effective means to track students' clinical experiences to monitor their progress toward competency goals. AIM: To validate an electronic scoring system that rates medical students' clinical notes for relevance to priority topics of the medical school curriculum. METHOD: The Vanderbilt School of Medicine Core Clinical Curriculum enumerates 25 core clinical problems (CCP) that graduating medical students must understand. Medical students upload clinical notes pertinent to each CCP to a web-based dashboard, but criteria for determining relevance of a note and consistent uploading practices by students are lacking. The Vanderbilt Learning Portfolio (VLP) system automates both tasks by rating relevance for each CCP and uploading the note to the student's electronic dashboard. We validated this electronic scoring system by comparing the relevance of 265 clinical notes written by third year medical students to each of the 25 core patient problems as scored by VLP verses an expert panel of raters. RESULTS: We established the threshold score which yielded 75% positive prediction of relevance for 16 of the 25 clinical problems to expert opinion. DISCUSSION: Automated scoring of student's clinical notes provides a novel, efficient and standardized means of tracking student's progress toward institutional competency goals.

Potent inhibitors of phosphatidylinositol 3 (PI3) kinase that have antiproliferative activity only when delivered as prodrug forms.

Prodrugs for PI3K: A series of substituted analogues of the phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 were prepared and found to potently inhibit the isolated enzyme but not MCF7 cell proliferation. Two tetrazolyl-substituted analogues were further derivatized as prodrugs resulting in restoration of cell-based activity. These data provide a conceptual model for development of tumor-targeting prodrug forms of cell-impermeable PI3K inhibitors.

A phase I study of cetuximab in combination with gemcitabine and radiation for locally advanced pancreatic cancer.

BACKGROUND: Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR). The primary goal of this phase I study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine when combined with cetuximab plus radiation in patients with locally advanced pancreatic cancer. PATIENTS AND METHODS: Patients with locally unresectable adenocarcinoma of the pancreas were treated with gemcitabine (200 mg/m(2)/week before dose escalation) plus cetuximab (400 mg/m(2) loading dose, 250 mg/m(2) weekly maintenance dose) concurrent with radiation (50.4 Gy). RESULTS: Nine patients were enrolled in the study. One withdrew due to declining performance status before receiving any therapy. Grade 4 allergic reactions to cetuximab caused the withdrawal of 2 patients. Another patient had elevated liver function test results and a stroke after his loading dose of cetuximab. Grade 3 or 4 toxicity developed in 3 of the remaining 5 patients treated with the level 1 dose. Therefore, no further dose escalations were planned. Grade 3 toxicities included nausea, vomiting, ileus, and pneumonitis. One patient had grade 4 diarrhea. CONCLUSIONS: The combination of cetuximab, gemcitabine, and radiation resulted in significant toxicity. A recommended phase II dose could not be determined.

Different baseline characteristics and different outcomes of HIV-infected patients receiving HAART through clinical trials compared with routine care in Mexico.

BACKGROUND: The efficacy of antiretroviral therapy (ART) has been established through clinical trials (CTs). However, selection bias and differences can limit their applicability to the general population. METHODS: All treatment-naive HIV-infected patients who began ART in routine care (RC) between 2000 and 2008 were compared with all patients who initiated ART through a CT in terms of incidence of virological failure (VF), increase in CD4(+) count, mortality rate, and loss to follow-up (LTFU). RESULTS: At baseline, the RC group had less years of education, higher unemployment rate, higher proportion of females (14.2 vs. 5.7%; P < 0.01), lower median CD4(+) (97 vs. 158 cells/µL; P < 0.01), and lower proportion of patients with hemoglobin >12 g/dL (74 vs. 83%, P = 0.04). VF at week 48 was less frequent in the CT compared with the RC group (1.8% vs. 6.21%, P = 0.02). In multivariate analysis, participation in CT [odds ratio (OR): 0.20, 95% confidence interval (CI): 0.04 to 0.91, P = 0.03], hemoglobin >12 g/dL (OR: 0.29, 95% CI 0.09-0.89, P = 0.03), and receiving an optimal highly active antiretroviral therapy regimen (OR: 0.09, 95% CI: 0.01 to 0.52, P < 0.01) remained associated with lower risk of VF. All cause mortality was 0.017 (95% CI: 0.002 to 0.122) versus 0.094 (95% CI: 0.053 to 0.17) deaths per 1000 person-days in the CT group and in the RC group, respectively (P = 0.05). No differences were found in the proportion of patients LTFU. CONCLUSIONS: Receiving ART through CT was associated with lower probability of VF, lower mortality (probably related to less severe clinical characteristics at baseline), and similar rates of LTFU than RC.