The structural characterization and hydroformylation activity of the tri-rhodium complex [Rh-3(mu(2)-dppm)(2)(mu(2)-CO)(3)(K-1-CO)(3)]BF4

Rh-2(cod)(2)(mu(2)-dppm)(mu(2)-Cl)]BF4 (1) rearranges under carbon monoxide to give [Rh-3(mu(2)-dppm)(2)-(mu(2)-CO)(3)(K-1-CO)(3)]BF4 (2). Complex 2 has been structurally characterized by single crystal X-ray crystallography. The hydroformylation activities of 1 and 2 were compared for substrates styrene and 1-hexene and the activity of 2 found to be unexpectedly high.

The control of social attention from 1 to 4 months

The control of social attention during early infancy was investigated in two studies. In both studies, an adult turned towards one of two targets within the infant's immediate visual field. We tested: (a) whether infants were able to follow the direction of the adult's head turn; and (b) whether following a head turn was accompanied by further gaze shifts between experimenter and target. In the first study, 1-month-olds did not demonstrate attention following at the group level. In addition, those infants who turned towards the same target remained fixed on it and did not shift attention again. In Study 2, we tested infants longitudinally at 2-4 months. At the group level, infants followed the adult's head turn at 3 and 4 months but not at 2 months. Those infants who turned towards the same target at 3 and 4 months also shifted gaze back and forth between experimenter and target. By 3 months, infants seem able to capitalize on the social environment to disengage and distribute attention more flexibly. The results support the claim that the control of social attention begins in early infancy, and are consistent with the hypothesis that following the attention of other people is dependent on the development of disengagement skills.

Platinum(II) phosphine and orotate complexes with aminopyridine co-ligands, and their molecular recognition via hydrogen bonding

The new complexes [Pt(dppp)(py)(2)][OTf](2), 1, [Pt(dppp)(2-ap)(2)][OTf](2), 2, [(dppp)Pt(mu -OH){mu -NH(C5H3N)NH2}Pt(dppp)][OTf](2), 3 (py=pyridine, 2-ap=2-aminopyridine, NH(C5H3N)NH2=2,6-diaminopyridine anion, dppp = 1,3-bis(diphenylphosphino)propane, OTf=O3SCF3) have been prepared via reactions between [Pt(dppp)(OTf)(2)] and pyridine, 2-aminopyridine or 2,6-diaminopyridine (2,6-dap) respectively. The amines exhibit a range of co-ordination modes. Pyridine and 2-aminopyridine co-ordinate to platinum through endo-nitrogen atoms in complexes 1 and 2, the latter existing as a pair of rotomers due to the steric hindrance introduced by the 2-substituent. However, 2,6-diaminopyridine co-ordinates to platinum through the exo-nitrogen of one amino group, to give the unusual mu -amido complex 3. Reaction of the known orotate chelate complex [Pt(PEt3)(2)(N,O-HL)] [HL=orotate, the dianion of 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid (orotic acid)] with 2,6-dap gave [Pt(PEt3)(2)(2,6-dap)(N-HL)] 4, which contains an unconventional monodentate orotate ligand. In this co-ordination mode the orotate retains an ADA hydrogen bonding site and was found to co-crystallise with 2,6-dap via complementary ADA:DAD triple hydrogen bonds to give [Pt(PEt3)(2)(N-HL)(2,6-dap)].2,6-dap, 5. Complex 5 exhibits a helical chain structure of associated [1+1] adducts in the solid state.

Orotate complexes of rhodium(I) and iridium(I): effect of coligand, counter ion, and solvent of crystallisation on association via complementary hydrogen bonding

The new complexes [NEt3H][M(HL)(cod)] (M = Rh 1 or Ir 2; H3L = 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid, erotic acid; cod = cycloocta-1,5-diene) have been prepared by the reaction between [M2Cl2(cod)(2)] and erotic acid in dichloromethane in the presence of Ag2O and NEt3. They crystallise as dichloromethane adducts 1 . CH2Cl2 and 2 . CH2Cl2 from dichloromethane-hexane solutions. These isomorphous structures contain doubly hydrogen-bonded dimers, with additional hydrogen bonding to NEt3H+ cations and bridging CH2Cl2 molecules to form tapes. The use of (NBu4OH)-O-n instead of NEt3 gave the related complex [NBu4n][Rh(HL)(cod)] 1' which has an innocent cation not capable of forming strong hydrogen bonds and in contrast to 1 exists as discrete doubly hydrogen-bonded dimers. Complex 1' cocrystallises with 2,6-diaminopyridine (dap) via complementary triple hydrogen bonds to give [NBu4n][Rh(HL)(cod)]. dap . CH2Cl2 3. Complex 3 exhibits an extended sheet structure of associated [2 + 2] units, with layers of NBu4n, cations separating the sheets. These structural data together with those reported previously for platinum orotate complexes suggest that the steric requirements of the other ligands co-ordinated to the metal are important in influencing their hydrogen-bonding abilities. The solvent of crystallisation, the hydrogen-bonding propensity of the coligand and the nature of the counter ion also determine the type of association in the solid state.

Synthesis and in Vitro and in Vivo Evaluation of a Series of Dihydroisocoumarin Derivatives Conjugated with Fatty Acids, Alcohols, and Amines as Potential Anticancer Agents

In this paper, we report the synthesis and biological activity of a series of dihydroisocoumarin analogues Conjugated with fatty acids, alcohols, or amines, of varying hydrocarbon chain length and degree of unsaturation, to (he dihydroisocoumarins, kigelin and mellein, at the C-7 and C-8 positions on the core dihydroisocoumarin structure. These compounds were evaluated for their antiproliferative activity against human breast cancer (MCF-7 and MDA-MB-468) and melanoma cells (SK-MEL-28 and Malme-3M) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Two compounds Conjugated with gamma-linolenyl alcohol (18:3 n-6) demonstrated potent antiproliferative activity in vitro with one of these 4-hydroxy-3-oxo-1.3-dihydro-isobenzofuran-5-carboxylic acid octadeca-6,9,12-trienyl ester, demonstrating significant antitumor activity in vivo ill a number of human tumor xenograft models.

PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: A systematic review

Background: Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed. Methods: Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer-specific survival, and overall survival. Results: In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2- positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76-4.41; P <0.001) and had poorer colorectal cancer-specific survival (n = 7; HR, 1.36; 95% CI, 1.02-1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancerspecific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n= 16; pooled unadjusted HR, 1.30; 95% CI, 0.94-1.79; P=0.11) and (n=9; pooled adjusted HR, 1.02; 95% CI, 0.72-1.45; P = 0.91)]. Conclusions: PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer-specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely. Impact: There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required. © 2013 AACR.

Transcutaneous sacral neurostimulation for irritative voiding dysfunction

with refractory irritative voiding dysfunction. Following an initial response, patients may successfully apply this treatment themselves to ensure long-term relief. Objective: Patients with irritative voiding dysfunction are often unresponsive to standard clinical treatment. We evaluated the response of such individuals to transcutaneous electrical stimulation of the third sacral nerve. Methods: 32 patients with refractory irritative voiding dysfunction (31 female and 1 male; mean age 47 years) were recruited to the study. Ambulatory transcutaneous electrical neurostimulation was applied bilaterally to the third sacral dermatomes for 1 week. Symptoms of frequency, nocturia, urgency, and bladder pain were scored by each patient throughout and up to 6 months following treatment. Results: The mean daytime frequency was reduced from 11.3 to 7.96 (p = 0.01). Nocturia episodes were reduced from a mean of 2.6 to 1.8 (p = 0.01). Urgency and bladder pain mean symptom scores were reduced from 5.97 to 4.89 and from 1.48 to 0.64, respectively. After stopping therapy, symptoms returned to pretreatment levels within 2 weeks in 40% of the patients and within 6 months in 100%, Three patients who continued with neurostimulation remained satisfied with this treatment modality at 6 months. Conclusions: Transcutaneous third sacral nerve stimulation may be an effective and noninvasive ambulatory technique for the treatment of patients with refractory irritative voiding dysfunction. Following an initial response, patients may successfully apply this treatment themselves to ensure long-term relief.

Impact of geometric variations on delivered dose in highly focused single vocal cord IMRT

Purpose. To investigate the robustness of single vocal cord intensity modulated radiation therapy (IMRT) treatment plans for set-up errors, respiration, and deformation. Material and methods. Four-dimensional computed tomography (4D-CT) scans of 10 early glottic carcinoma patients, previously treated with conventional techniques, were used in this simulation study. For each patient a pre-treatment 4D-CT was used for IMRT planning, generating a reference dose distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up errors was simulated by applying shifts of ± 2 mm to the planning CT scans, followed by dose re-calculation with original beam segments, MUs, etc. Effects of respiration and deformation were determined utilizing extreme inhale and exhale CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively. All doses were calculated using Monte Carlo dose simulations. Results. Considering all investigated geometrical perturbations, reductions in the clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform dose (gEUD) were limited to 1.2 ± 2.2%, 2.4 ± 2.9%, 0.2 ± 1.8%, and 0.6 ± 1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%, and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal cord DMean, gEUD, and V40 Gy were 38.2 ± 6.0 Gy, 43.4 ± 5.6 Gy, and 42.7 ± 14.9%. With perturbations these values changed by -0.1 ± 4.3 Gy, 0.1 ± 4.0 Gy, and -1.0 ± 9.6%, respectively. Conclusions. On average, CTV dose reductions due to geometrical perturbations were very low, and sparing of the CL vocal cord was maintained. In a few observations (6 of 103 simulated situations), the near-minimum CTV-dose was around 90%, requiring attention in deciding on a future clinical protocol.