bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Coherent Description of Diffusion‐Influenced Fluorescence Quenching Experiments
Authors: Rosspeintner Arnulf , Kattnig Daniel R. , Angulo Gonzalo , Landgraf Stephan , Grampp Günter , Cuetos Alejandro
Published: May 2007

The fluorescence quenching by electron transfer of a fluorophore, 2,5‐bis(dimethylamino)‐1,3‐benzenedicarbonitrile, to 1,3‐dimethyl‐2‐nitrobenzene, has been studied by means of time‐resolved and steady‐state experiments at different viscosities and up to large quencher concentrations. Differential Encounter Theory (DET) has been used to rationalize the results, in combination with electron transfer modelled by the Marcus theory. Additionally, the solvent structure and the hydrodynamic effect on the diffusion coefficient have been taken into account. Any simpler model failed to simultaneously fit all the results. The large number of quencher concentrations used is crucial to unambiguously extract the electron transfer parameters.
On the Chemical Reaction of Matter with Antimatter
Authors: Lodi Rizzini Evandro , Venturelli Luca , Zurlo Nicola
Published: May 2007

A chemical reaction between the building block antiatomic nucleus, the antiproton (p̄ or ${\bar H^ - }$ in chemical notation), and the hydrogen molecular ion (${H_2^ + }$) has been observed by the ATHENA collaboration at CERN. The charged pair interact via the long‐range Coulomb force in the environment of a Penning trap which is purpose‐built to observe antiproton interactions. The net result of the very low energy collision of the pair is the creation of an antiproton–proton bound state, known as protonium (Pn), together with the liberation of a hydrogen atom. The Pn is formed in a highly excited, metastable, state with a lifetime against annihilation of around 1 μs. Effects are observed related to the temperature of the ${H_2^ + }$ prior to the interaction, and this is discussed herein.
A Theoretical Study of Anion–π Interactions in Seven‐Membered Rings
Authors: Quiñonero David , Frontera Antonio , Escudero Daniel , Ballester Pablo , Costa Antonio , Deyà Pere M.
Published: May 2007

Several complexes of tropylium (1) with anions are optimized at the RI‐MP2(full)/6‐31++G** level of theory. This binding unit can interact very favorably with anions, and it combines the strength of the electrostatic interaction with the directionality of the anion–π interaction. The complexes of1with anions are characterized by means of the Bader theory of “atoms‐in‐molecules,” and the physical nature of the interaction has been analyzed by means of the molecular interaction potential with polarization tool. Experimental evidence of anion–π interactions involving seven‐membered rings has been found in the solid state.
Gas‐Phase Reactions Between Thiourea and Ca2+: New Evidence for the Formation of [Ca(NH3)]2+and Other Doubly Charged Species
Authors: Trujillo Cristina , Mó Otilia , Yáñez Manuel , Salpin Jean‐Yves , Tortajada Jeanine
Published: May 2007

The gas‐phase reactions between Ca2+and thiourea are investigated by means of electrospray ionization/mass spectrometry experiments. The MS/MS spectra of [Ca(thiourea)]2+complexes show the appearance of new doubly charged species formed by the loss of NH3and HNCS. Other intense peaks atm/z43, 56, 60, 73, 76 and 98 are also observed, and assigned to monocations produced in different coulomb‐explosion processes. The structures and bonding characteristics of the different stationary points of the [Ca(thiourea)]2+potential energy surface (PES) were theoretically studied by DFT calculations carried out at B3LYP/cc‐pWCVTZ level. The analysis of the topology of this PES permits to propose different mechanisms for the loss of ammonia and HNCS, and to identify, them/z43, 56, 60, 73, 76 and 98 peaks as H2NCNH+, CaNH2+, H2NCS+, CaSH+, thiourea+⋅and CaNCS+ions respectively. There are significant dissimilarities between the reactivity of urea and thiourea, which are related to the lower ionization energy of the latter, and to the fact that thioenols are intrinsically more stable than enols with respect to the corresponding keto forms.
Fractal response of physiological signals to stress conditions, environmental changes, and neurodegenerative diseases
Authors: Scafetta Nicola , Moon Richard E. , West Bruce J.
Published: May 2007

In the past two decades the biomedical community has witnessed several applications of nonlinear system theory to the analysis of biomedical time series and the development of nonlinear dynamic models. The development of this area of medicine can best be described as nonlinear and fractal physiology. These studies have been intended to develop more reliable methodologies for understanding how biological systems respond to peculiar altered conditions induced by internal stress, environment stress, and/or disease. Herein, we summarize the theory and some of our results showing the fractal dependency on different conditions of physiological signals such as inter‐breath intervals, heart inter‐beat intervals, and human stride intervals. © 2007 Wiley Periodicals, Inc. Complexity 12: 12–17, 2007
Generation of mice deficient for Lbx2, a gene expressed in the urogenital system, nervous system, and Pax3 dependent tissues
Authors: Wei Ke , Chen Jiyuan , Akrami Kevan , Sekhon Rashmi , Chen Fabian
Published: May 2007

Lbx2 is a member of the ladybird family of homeobox genes. The first murine ortholog identified, Lbx1, is required for hypaxial musculature and dorsal spinal cord neuron development. The second murine ortholog, Lbx2, is expressed in the developing urogenital and nervous systems. To elucidate the function of Lbx2, we generated a gene‐targeted allele of Lbx2 in mice. Lbx2 deficiency did not impair mouse development, and Lbx2 null mice appeared healthy and fertile. Replacement of Lbx2 by the lacZ gene provides a valuable histological marker for Lbx2‐expressing cells. Given the important role of Pax3 in neural crest, we intercrossed our Lbx2 deficient mice with Splotch Pax3 mutant mice to determine if Pax3 affects Lbx2 expression. There was reduced Lbx2 expression in dorsal root ganglia and cranial nerve ganglia with Pax3 deficiency, but not in the genital tubercle. This suggested that Pax3 is required for Lbx2 expression in affected neural crest‐derived tissues. genesis 45:361–368, 2007. Published 2007 Wiley‐Liss, Inc.
Synthesis of Cycloruthenated Compounds as Potential Anticancer Agents
Authors: Leyva Lida , Sirlin Claude , Rubio Laura , Franco Cecilia , Le Lagadec Ronan , Spencer John , Bischoff Pierre , Gaiddon Christian , Loeffler Jean‐Philippe , Pfeffer Michel
Published: May 2007

A library of 19 cycloruthenated derivatives is constructed by making use of the well‐known cyclometalation reaction. Their geometries are modified in a straightforward manner by addition of either mono‐ or bidentate ligands, such as bipyridine, phenanthroline, 1,2‐bis(diphenylphosphanyl)ethane, dimethylphenylphosphane, triphenylphosphane, and 1,3,5‐triaza‐7‐phosphatricyclo[3.3.1.1]decane (PTA) ligands, to cationic cycloruthenated centers. The antitumor properties of the compounds thus obtained are investigated in order to compare them with recently reported ruthenium complexes and cisplatin. IC50values against mammalian cells (A‐172, HCT‐116, and RDM‐4) are determined for the library compounds and some of them, such as those derived from orthoruthenated phenylpyridine and a bidentate N,N ligand, display activity of the same order of magnitude as cisplatin. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis and Photophysical Properties of Bis‐Cyclometallated Iridium(III)–Styryl Complexes and Their Saturated Analogues
Authors: Lepeltier Marc , Lee Terence Kwok‐Ming , Lo Kenneth Kam‐Wing , Toupet Loic , Le Bozec Hubert , Guerchais Véronique
Published: May 2007

This manuscript reports the synthesis and photophysical investigation of a series of IrIII complexes Ir(C∧N)2(O∧O) which are functionalized in the para position of the pyridine ring by styryl groups substituted with electron‐donor and ‐acceptor end groups. The saturated derivative Ir(C∧N‐ppy‐4‐CH2CH2C6H4OMe)2(O∧O‐acac) (4a‐H2) was formed from [Ir(C∧N‐ppy‐4‐CH=CHC6H4OMe)2]2(μ‐Cl)2 (3a) at 140 °C, whereas at 80 °C the parent unsaturated complexes Ir(C∧N‐ppy‐4‐CH=CHC6H4R)2(O∧O) [OO = acac, R = OMe (4a), NEt2 (4b), H (4c), NO2 (4d); OO = dpm, R = OMe (5a), NEt2 (5b)] were isolated. The saturated complex 4a‐H2 exhibits intense green emission with a 36 % quantum yield at 298 K. The styryl complexes 4a–4d, 5a and 5b are very weakly emissive at 298 K, but show intense red luminescence in alcohol glass at 77 K. The amino‐ and nitro‐substituted complexes 4b and 4d give low‐energy emission (λem = 651 and 647 nm, respectively). The emissive states of these complexes are believed to possess predominant triplet intra‐ligand charge‐transfer (3ILCT) and metal‐to‐ligand charge‐transfer (3MLCT) character, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis, Characterization and Stability of Spirodiene Complexes of Molybdenum(II): New Route to ansa‐Molybdenocene and Ring‐Functionalized Molybdenocene Compounds
Authors: Honzíček Jan , Almeida Paz Filipe A. , Romão Carlos C.
Published: May 2007

The reactions of [Mo(CO)2(Cp)(NCCH3)2][BF4] (1) with spiro[2.4]hepta‐4,6‐diene and spiro[4.4]nona‐1,3‐diene give the complexes [Mo{η4‐C5H4(CH2)2}(CO)2(Cp)][BF4] (3) and [Mo{η4‐C5H4(CH2)4}(CO)2(Cp)][BF4] (4), respectively. [Mo{η4‐C5H4(CH2)2}(CO)2(Cp)][BF4] (3) is stable towards ring opening at room temperature, but its formation is accompanied by small amounts of ring‐opening products [Mo(η5‐C5H4CH2‐η1‐CH2)(CO)(Cp)][BF4] (5) and [Mo{η5‐C5H4(CH2)2‐η1‐CO}(CO)(Cp)][BF4] (6). With 1,1‐dimethyl‐spiro[2.4]hepta‐4,6‐diene, two isomers with the formula [Mo{η4‐C5H4CH2C(CH3)2}(CO)2(Cp)][BF4] are formed (7 and 8). While the endo‐isomer 7 is stable towards ring opening, the exo‐isomer 8 slowly rearranges to the ring‐opened product [Mo{η5‐C5H4C(CH3)2CH2‐η1‐CO}(CO)(Cp)][BF4] (9). The reaction of [Mo(CO)2(Ind)(NCCH3)2][BF4] (2) with spiro[4.4]nona‐1,3‐diene also gives the diene coordinated species [Mo{η4‐C5H4(CH2)4}(CO)2(Ind)][BF4] (11), which is the first example of a structurally characterized, coordinated, unsubstituted spirodiene. In contrast, reaction of 2 with spiro[2.4]hepta‐4,6‐diene leads directly to the ansa‐cyclopentadienyl complex [Mo(η5‐C5H4CH2‐η1‐CH2)(CO)(Ind)][BF4] (12). Reaction of 12 with bromine or iodine leads to the formation of Cp‐substituted molybdenocene derivatives [Mo{η5‐C5H4(CH2)2X}(CO)(Ind)X][BF4] (13: X = Br, 14: X = I). The compounds [Mo(η5‐C5H4CH2‐η1‐CH2)(CO)(Ind)][BF4] (12) and [MoBr{η5‐C5H4(CH2)2Br}(CO)(Ind)][Br]·0.5H2O (13a) were structurally characterized, and they open the way to new functionalized molybdenocene complexes that have biological applications.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Substituent Effects on the Stereoelectronic and Chemical Properties of a Novel Phosphapalladacycle
Authors: Ng Joseph Kok‐Peng , Chen Shuli , Tan Geok‐Kheng , Leung Pak‐Hing
Published: May 2007

A novel phosphapalladacycle was prepared by direct cyclopalladation of the ligand (diphenylmethyl)diphenylphosphane (2). The corresponding μ‐chloro five‐membered phosphapalladacycle 3 was obtained by heating a toluene solution of 2 and Pd(OAc)2 followed by chloride ion metathesis. An optical resolution procedure was then employed by separation of the (S)‐prolinato derivatives 4 by fractional crystallization followed by treatment with dilute hydrochloric acid to yield both enantiopodes of the dimers 3 in the optically active forms. The current phosphapalladacycle was noted to display different properties with respect to the analogous phosphapalladacycle prepared from (diphenylmethyl)di‐tert‐butylphosphane. For instance, the phosphapalladacycle based on the (diphenylmethyl)di‐tert‐butylphosphane was shown to be conformationally rigid. In contrast, the analogous five‐membered phosphapalladacycle of phosphane 2 was noted to exist in both the δ and λ conformations in the solid state, while a flattened conformation was observed in solution. In addition, the (diphenylmethyl)di‐tert‐butylphosphane‐based phosphapalladacycle was noted to exhibit a much more improved regioselectivity towards ancillary ligands such as (S)‐prolinate and triphenylphosphane than 2. Furthermore, the μ‐chloro dimer 3 of the current palladacycle was shown to be lacking in thermodynamic stability of the Pd–C bond that was noted for the tBu analogue. In contrast, the Pd–C bonds of dimer 3 were immediately ruptured in the presence of concentrated HCl to give rise to the binuclear complex 5, in which the phosphane was coordinated in the η1‐P coordination mode.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Influence of the Polypyridyl (pp) Ligand Size on the DNA Binding Properties, Cytotoxicity and Cellular Uptake of Organoruthenium(II) Complexes of the Type [(η6‐C6Me6)Ru(L)(pp)]n+ [L = Cl, n = 1; L = (NH2)2CS, n = 2]
Authors: Schäfer Sven , Ott Ingo , Gust Ronald , Sheldrick William S.
Published: May 2007

The DNA binding of polypyridyl (pp) (η6‐hexamethylbenzene)ruthenium(II) complexes of the type [(η6‐C6Me6)RuCl(pp)](CF3SO3) (pp = phen, tap, dpq, dppz, dppn) 1–5 and [(η6‐C6Me6)Ru{(NH2)2CS}(pp)](CF3SO3)2 (pp = dpq, dppz, dppn) 6–8 has been studied by UV/Vis spectroscopy, circular dichroism and viscosity measurements. Complexes 3–5, 7 and 8 are potent cytotoxic agents towards the human cancer cell lines MCF‐7 and HT‐29. Stable intercalative binding into CT DNA is indicated for the dpq and dppz complexes by large increases ΔTm of 12–25 °C in the DNA thermal denaturation temperature for r = [complex]/[DNA] = 0.1. Large viscosity increases for DNA in the presence of 3 and 4 are also in accordance with this binding mode as are the pronounced hypochromic UV/Vis shifts for the π–π* transitions of the dppz ligands of 4 and 7 in the range 360–400 nm. A small ΔTm value of 2 °C and effectively unchanged viscosity suggest that Ru–N (nucleobase) coordinative binding is thermodynamically preferred for the larger polypyridyl ligand of 5 under equilibrium conditions, as is also the case for the small ligands phen and tap in complexes 1 and 2. CD spectra indicate that the B DNA conformation is essentially retained for interaction with the chloro complexes 1–5 but that very significant distortions occur for the thiourea complexes 6–8. The in vitro cytotoxicities of the chloro complexes 3–5 are dependent on the size of the polypyridyl ligand with IC50 values increasing in the order dppn < dppz < dpq: for instance IC50 values of 11.1, 2.12, and 0.13 μM were determined for 3–5 towards MCF‐7. These values correlate well with the cellular uptake efficiency which increases from 1.1 over 146.6 to 906.7 ng(Ru)/mg (protein) within the series 3–5. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Recent Developments in Phosphole‐Containing Oligo‐ and Polythiophene Materials
Authors: Hobbs Matthew G. , Baumgartner Thomas
Published: May 2007

The introduction of phosphorus‐containing moieties into π‐conjugated thiophene materials has been found to provide materials with strongly optimized and highly tunable optoelectronic features compared to their native thiophene counterparts. 2,5‐Diaryl‐ and 2,5‐bis(heteroaryl)phospholes as well as fused tricyclic dithieno[3,2‐b:2′,3′‐d]phospholes represent two very valuable building blocks for organic electronics as their intriguing features can be altered systematically by several, in part unique, methodologies. The potential scope of these modifications has been determined by comprehensive investigations of their structure–property relationships via suitable molecular model compounds. Onseveral occasions, these observations could successfully be transposed to corresponding polymers that are often difficult to characterize independently. The same is true for the first organic light‐emitting diodes (OLEDs) based on a phosphole scaffold, whose properties could also be predicted successfully. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Heptakis[2,3‐di‐O‐methyl‐6‐O‐(L‐valine‐tert‐butylamide‐Nα‐ylcarbonylmethyl)]‐β‐cyclodextrin: a New Multifunctional Cyclodextrin CSA for the NMR Enantiodiscrimination of Polar and Apolar Substrates
Authors: Uccello‐Barretta Gloria , Nazzi Samuele , Balzano Federica , Levkin Pavel A. , Schurig Volker , Salvadori Piero
Published: May 2007

Heptakis[2,3‐di‐O‐methyl‐6‐O‐(L‐valine‐tert‐butylamide‐Nα‐ylcarbonylmethyl)]‐β‐cyclodextrin with methyl groups on the secondary sites and a diamide chiral selector on the primary ones showed considerable utility as a CSA in the NMR enantiodiscrimination of a wide spectrum of amino acid derivatives, while also allowing trisubstituted allenes to be enantiodiscriminated. Enantiodiscrimination processes were investigated by Diffusion‐Ordered SpectroscopY (DOSY). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Base‐Catalyzed Anti‐Markovnikov Hydroamination of Vinylarenes – Scope, Limitations and Computational Studies
Authors: Horrillo‐Martínez Patricia , Hultzsch Kai C. , Gil Adrià , Branchadell Vicenç
Published: May 2007

The hydroamination of vinylarenes with primary and secondary amines was studied with catalytic amounts as low as 2 mol‐% of LiN(SiMe3)2/TMEDA. Reactions proceeded readily at 120 °C in the absence of solvent to give selective anti‐Markovnikov addition. Slow addition was observed at 25 °C with either electron‐deficient p‐chlorostyrene or secondary cyclic amines such as pyrrolidine, piperidine, or morpholine. Primary amines were prone to a second hydroamination reaction to form tertiary amine byproducts. The selectivity for the mono(hydroamination) products could be improved with a two‐fold excess of the amine. KN(SiMe3)2 showed higher catalytic activity but lower selectivity in comparison to that of LiN(SiMe3)2, resulting in undesired C–H‐activation byproducts. The mechanism of the lithium‐catalyzed hydroamination and the influence of TMEDA was studied with density functional theory. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Stereoselective Synthesis of Hexahydroisobenzofuran‐4(1H)‐ones from Chiral Substituted Cyclohex‐2‐enyl Carbamates via Asymmetric Homoaldol Reaction and THF Cyclocondensation
Authors: Becker Jochen , Fröhlich Roland , Kataeva Olga , Hoppe Dieter
Published: May 2007

The diastereofacial selectivity of the homoaldol reaction of metalated substituted cyclohex‐2‐enyl carbamates with aldehydes is controlled by the nature of the metal complex. Allyllithiums yield syn‐configured products whereas transmetallation to Ti(NEt2)3 gives access to anti‐configured 3‐(1‐hydroxyalkyl)cyclohexenes. The syn‐configured homoaldol products were transformed into annulated all‐cis‐tetrahydrofurans by Lewis acid‐mediated cyclocondensation with aldehydes. Analogous cis,trans,cis‐substituted hexahydroisobenzofuran‐4(1H)‐ones, the core structure of many biologically active natural products, were synthesized starting from anti‐configured homoaldol products. The configurations of the products were determined by 1H NMR coupling constants, nOe‐studies, and X‐ray crystal structure analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Cover Picture: From Allenes to Tetracenes: A Synthetic and Structural Study of Silyl‐ and Halo‐Allenes and Their Dimers (Eur. J. Org. Chem. 16/2007)
Authors: Banide Emilie V. , Molloy Bevin C. , Ortin Yannick , Müller‐Bunz Helge , McGlinchey Michael J.
Published: May 2007

The cover picture shows the entrance to the World Heritage Site at Newgrange, a 5000‐year‐old Neolithic passage tomb, situated near Dublin. The background depicts a twofold symmetric spiral engraving on the entrance stone and provides an appropriate motif for the sequential transformation of 9‐(trimethylsilylethynyl)‐9H‐fluoren‐9‐ol, via 3,3‐(biphenyl‐2,2′‐diyl)‐1‐(trimethylsilyl)allene, into a series of sterically crowded head‐to‐tail and tail‐to‐tail silyl‐allene dimers with unusually long carbon–carbon and carbon–silicon bonds. Removal of the silyl substituents culminates in the formation of the bis(alkylidene)cyclobutane shown, whose intrinsic C2 symmetry arises solely from the overlap of fluorenylidene fragments with very large wingspans. Details of this work are described in the article by M. J. McGlinchey et al. on p. 2611 ff.
Combined cup loading, bis(2‐hydroxyethyl) disulfide, and protein precipitation protocols to improve the alkaline proteome of Lactobacillus hilgardii
Authors: Lamberti Cristina , Pessione Enrica , Giuffrida Maria G. , Mazzoli Roberto , Barello Cristina , Conti Amedeo , Giunta Carlo
Published: May 2007

Despite the large number of papers dealing with bacterial proteomes, very few include information about proteins with alkaline pI's, because of the limits inherent in 2‐DE technology. Nonetheless, analyses of in silico proteomes of many prokaryotes show a bimodal distribution of their proteins based on their pI's; the most crowded areas lying between pI 4–7 and 9–11. The aim of the present research was to set up a general, simple, and standardizable 2‐DE protocol suitable for studying the alkaline proteome of Lactobacillus hilgardii, a Gram‐positive bacillus isolated from wine. The method has also been tested on a Gram‐negative bacterium able to degrade aromatic pollutants, Acinetobacter radioresistens S13. Optimization of the method was mainly focused on improving protein extraction and IEF (pI 6–11) separation protocols. Concerning IEF, different methods for sample loading (in‐gel rehydration and cup loading), and different reducing agents (DTT and bis(2‐hydroxyethyl) disulfide (HED)) were tested and compared. The proposed protocol was found to resolve efficiently alkaline proteins from both of our Lactobacillus and Acinetobacter strains, in spite of their different external layers, thus, enabling a more comprehensive study of their proteomes.
Genome‐wide array‐based comparative genomic hybridization of ocular marginal zone B cell lymphoma: Comparison with pulmonary and nodal marginal zone B cell lymphoma
Authors: Kim Won Seog , Honma Keiichiro , Karnan Sivasundaram , Tagawa Hiroyuki , Kim Yoon Duck , Oh Young Lyun , Seto Masao , Ko Young Hyeh
Published: May 2007

The genetic changes in marginal zone B cell lymphomas (MZBCL) vary according to the anatomical region. This study aimed to investigate genomic aberrations in ocular MZBCL and to compare them with those of tumors from other anatomical sites. The study population comprised 24 cases of primary ocular MZBCL, 11 pulmonary MZBCL, and seven nodal MZBCL. For array CGH, fresh tumor tissues were analyzed with a genome‐wide scanning array containing 2,304 BAC/PAC clones which cover the whole human genome at a resolution of 1.3 Mb. FISH analysis for MALT1 gene alteration was performed for ocular and nodal MZBCL and RT‐PCR for the detection of API2‐MALT1 transcripts was performed for pulmonary MZBCL. The recurrent genomic alterations in ocular MZBCL were losses of chromosome bands 6q23.3 (9/24, 38%), 7q36.3 (2/24, 8%), and 13q34 (2/24, 8%), and gains of chromosomes 3 (9/24, 38%), and 15 (4/24, 16%), and chromosome arms 18q (4/24, 16%), and 6p (2/24, 8%). The t(11;18)(q21;q21) was not detected. The genomic alterations of pulmonary MZBCL included recurrent loss of 18q21 (2/11, 19%). A t(11;18)(q21;q21) fusion transcript was detected in five out of eight cases (63%). Nodal MZBCL showed neither recurrent genome alterations nor any change in MALT1 gene copy number. In conclusion, the array CGH profile of ocular MZBCL is distinct from those of pulmonary and nodal MZBCL. Deletion of chromosome band 6q23.3 in ocular MZBCL is a novel finding and may constitute a crucial genetic alteration in the pathogenesis of ocular MZBCL. © 2007 Wiley‐Liss, Inc.
Early Triassic carbon isotope excursions from South China: proxies for devastation and restoration of marine ecosystems following the end‐Permian mass extinction
Authors: Jinnan Tong , Jingxun Zuo , Z.Q. Chen
Published: May 2007

Early Triassic carbon isotopes are measured based on 1422 carbonate bulk samples from 10 Lower Triassic sections in different palaeogeographic settings in South China. Early Triassic fluctuation ofδ13C is used as a proxy for environmental change to discuss the devastation and restoration of marine ecosystems following the biggest Phanerozoic mass extinction at the end of the Permian. Early Triassicδ13C profiles derived from various depositional settings in South China yield comparable excursion patterns. A dramatic negative shift ofδ13C across the Permian/Triassic boundary is followed by a moderate increase inδ13C values throughout the Induan. A positiveδ13C anomaly occurs near the Induan/Olenekian boundary, followed by a Smithian interval of lowerδ13C values. A distinct positive shift inδ13C coincides with the Smithian/Spathian boundary, and is followed by a high Spathian plateau ofδ13C values. Thus the distinctδ13C anomalies coincide well with key stratigraphic boundaries.

Early Triassic intervals of lowδ13C values correspond to a decline in benthic generic diversity in South China and intervals of highδ13C values are coupled with an increase in biodiversity. The Early Triassic fluctuations ofδ13C profiles are good proxies for perturbations of ecologic environments, indicating multiple phases of devastation–restoration of marine ecosystems punctuated by several unexpected extraneous events such as volcanic activity. The initial restoration of marine ecosystems may have occurred earlier in the Induan and the ecosystems were subsequently destroyed during the Smithian. Biotic and environmental recoveries occurred at the Spathian, while the ecosystems eventually returned to normal levels in the early Middle Triassic. Copyright © 2007 John Wiley & Sons, Ltd.
Screening for diabetic retinopathy: A relative cost‐effectiveness analysis of alternative modalities and strategies
Authors: Sculpher M. J. , Buxton M. J. , Ferguson B. A. , Spiegelhalter D. J. , Kirby A. J.
Published: May 2007

Diabetic retinopathy is the most common cause of blindness among adults of working age in the UK. If the disease is detected early effective treatment can be provided and this has resulted in calls for a systematic national screening programme. Using data on the screening of 3423 diabetics collected as part of an experimental programme in three UK centres, the relative cost‐effectiveness of various screening options is assessed. The paper utilises direct evidence on a number of single modality screening options, including ophthalmoscopy undertaken by general practitioners or ophthalmic opticians, and non‐mydriatic photography. With the objective of increasing the sensitivity of screening and using data collected in the study, options based on two further potential screening strategies are modelled and evaluated: combined screening using both ophthalmoscopy and non‐mydriatic photography; and selective screening where high‐risk diabetics are directly referred to an ophthalmologist and lowrisk cases are either left unscreened or are screened by one of the single or combined modality screening options. Given the objective of early detection, effectiveness is assessed in terms of the sensitivity and specificity of the referral decisions of screening options. Both health service and private resource costs of the various screening options are estimated, the latter in terms of travel and the opportunity cost of time. Cost effectiveness is evaluated in terms of the expected cost per true positive case of diabetic retinopathy referred by the screening options. To narrow the choice between the options, those subject to three‐way domination with respect to the three choice variables of sensitivity, specificity and expected cost per true positive are excluded. Amongst the remaining options, the choice is dependent on the trade‐off between the higher specifics of unselective single modality screening options and the higher sensitivities and lower expected costs per true positive case detected of combined modality and selective screening options.
Cost savings in mass population screening for colorectal cancer resulting from the early detection and excision of adenomas
Authors: Whynes David K. , Walker Andrew R. , Hardcastle Jack D.
Published: May 2007

The widely‐accepted hypothesis of a development sequence from colorectal adenoma to carcinoma is felt by clinicians to legitimate adenoma excision during routine colonoscopic investigation. Using published data on adenoma development, and adenoma prevalence data derived from the Nottingham colorectal cancer screening trial, the number of carcinomas prevented by early excision as a result of screening is predicted. The cost‐effectiveness of early excision is then evaluated with reference to the expected treatment costs saved. These cost savings are found to represent a discount on the overall costs of mass population screening for colorectal cancer.
Forces for reforming the U.S. health care system: A review of the cost and access issues
Authors: Browning Susan M.
Published: May 2007

In recent years, a spate of health care reform proposals have emerged on the American agenda. Although the elements of the reform proposals often vary substantially, most of the initiatives are fuelled by two common concerns: rising health care expenditures and a growing uninsured population. National health spending, for example, commands an increasing share of U.S. gross national product despite numerous cost‐containment efforts initiated by public and private payers throughout the 1980s. And the uninsured population continues to grow—by an estimated 30 percent between 1978 and 1989. To facilitate understanding of the public policy options being considered to address these concerns, the article examines U.S. health care expenditure data and some of the causes of rising health care costs. The article also discusses the demographic characteristics of the uninsured population, the reasons why they lack health coverage, and the health consequences associated with being uninsured.
Proposals to reform the U.S. health care system: A critical review
Authors: Gaffney John C. , Browning Susan M. , Hirshfeld Edward B.
Published: May 2007

The objective is to provide an overview and analysis of the current discussion of ways to reform the U.S. health care system. A common analytic framework is needed to evaluate the alternative approaches that are being advocated. Such a framework, organized around seven general questions, is developed and discussed. The analytic framework is then applied to five specific reform proposals, selected to be representative of the range of options being considered. The results are used to identify the basic choices that are inherent in the current discussion of health system reform. A discussion of the political realities of the health system reform movement in the U.S. concludes that an incremental reform measure will be implemented at the federal level in the near future and that the reform measure will give the federal government increased control over the health care sector. However, the pressure for more fundamental reform will continue to grow.
Pooling international health care expenditure data
Authors: Gerdtham Ulf‐G.
Published: May 2007

The purpose of this paper is twofold. The first is to analyse the statistical relationship between real health care expenditure per capita and aggregate income, public share in finance, age‐dependency ratio and inflation. The second purpose deals with methodological problems involved in pooling health care expenditure data. The empirical work is based on pooled cross‐sectional, time‐series data for 22 OECD countries from 1972 to 1987. Public finance share and inflation were found to be associated with lower per capita health care expenditure. No consistent correlation was found between the age‐dependency ratio and health care expenditure. Contrary to results of earlier studies, we found that health care expenditure does not appear to be income (GDP) elastic. However, the results do not appear to be robust to changes in the time periods and countries included.
The cost and efficiency of public and private health care facilities in Ogun state, Nigeria
Authors: Wouters Annemarie
Published: May 2007

During the 1980s, Nigeria faced difficult economic conditions resulting in a severely constrained budget for public health services. To assess more carefully the costs and efficiency of the public and private health sectors, the Federal Ministry of Health in Nigeria undertook a comprehensive survey of health care facilities in Ogun State in 1987, the analysis of which is presented in this study. The findings suggest that there is potential to increase service delivery within existing budgets by more cost‐effective allocation of inputs. Many public and private providers are not operating at full technical capacity. It also appears that public facilities are not using cost‐minimizing combinations of high and low‐level health workers, in particular, too many low‐level staff are being used to support high‐level workers. The cost analysis indicates that there are short‐run increasing returns to scale for inpatient and nearly constant returns to scale for outpatient services. Economies of scope for joint production of inpatient and outpatient services are not being realized. A major implication of such analysis is that improved resource allocation decisions heavily depend on the existence of information systems at the health facility level which carefully integrate financial information with other appropriate and adequate measures of service inputs, health care quality, facility utilization and ultimately health status.
Sometimes sensitive, seldom specific: A review of the economics of screening
Authors: Cairns John , Shackley Phil
Published: May 2007

As the policy relevance of screening has increased, the application of the techniques of economic evaluation to screening has become widespread. This paper critically reviews the literature, and in so doing, highlights several ways in which future evaluations might be improved. These include: the adoption of a broader perspective regarding the questions to be addressed and the relevant margins; a reconsideration of the nature of the benefits and how they might be valued; and a greater emphasis being placed upon the role of individual behaviour and its potential impact on the outcome of economic evaluations.
Individual behaviour and tobacco consumption: A panel data approach
Authors: Labeaga Jose M.
Published: May 2007

This paper considers estimators of tobacco demand equations using Becker and Murphy's model of addiction with a complete panel of households for Spain. With these tools, we face two main problems: first, the endogeneity of past and future consumption and, second, the limited‐dependent variable. To control these problems simultaneously is difficult and we proceed to confront them separately. We follow an instrumental variable approach (which also allows us to control for measurement errors in variables and non‐independent effects) to tackle the first and we use a consistent within‐group procedure to obtain the parameter vector of the structural form, once we have estimated T‐Tobit models for the reduced form in order to deal with the limited‐dependent variable problem.
Econometric analyses of national health expenditures: Can positive economics help to answer normative questions?
Authors: McGuire Alistair , Parkin David , Hughes David , Gerard Karen
Published: May 2007

The size of national health care expenditure is an important research and policy issue. This paper reviews theoretical and empirical analyses of an implied optimal size for a health sector. Various economic theories are explicitly or implicitly invoked, but none is fully satisfactory. Theory provides, at best, a loose justification for empirical specifications of health sector behaviour. Nevertheless, this has a large and growing empirical research industry. The complexity of the issues provides an excuse for reliance on empirical analyses using ad hoc models.

The paper analyses aggregate time‐series data, using the cointegration approach, on health, health care expenditures and national income. Only one national model met both statistical criteria and showed a significant relationship: between potential life years lost and health care expenditure in the UK. The case for any general relationships remains unproven.

There is no objective scientific method to determine optimal health expenditure, nor should we expect one. However, positive analyses can help with normative questions. A better understanding of health expenditure determination would arise from better specification of the relationships, perhaps by analysis at a lower level of aggregation.
Health care expenditure and income in Europe
Authors: Murillo Carlos , Piatecki Cyrille , Saez Marc
Published: May 2007

In this work we have tried to analyse the variations in health care expenditure in all the countries of the European Community except Greece and Portugal. We have wanted to provide additional evidence on the empirical relationship between expenditure on health care and income. Our analysis, starting from the approach of Fuchs and Baumol, has been an extension of the traditional studies on health care international comparisons, in at least three directions: we have not imposed any restrictions on the price effects, we have analysed dynamic models instead of the cross‐sectional analysis and we have used proper deflators. We have deflated health care expenditure in each country by means of its sectoral price index and by the purchasing parity power of its currency, to allow international comparisons. In the former case we express health care in terms of ‘expenditure’, in the latter we express health care in terms of ‘weighted quantity’. Income elasticities, in the short and in the long‐run, have been estimated using econometric methods that allow us to obtain simultaneously equilibrium long‐run relationships, if any, and adjustment processes in the short‐run. We have found cointegrating relationships and we have estimated consistent estimators of the elasticities. The estimated income elasticities are greater than one in all the models analysed.
Financial incentives for physicians: The Quebec experience
Authors: Rochaix Lise
Published: May 2007

This paper presents an empirical investigation of physician labour supply, based on a two‐stage budgeting model, drawing on an analogy with consumer theory. Physicians' trade‐offs between income and leisure constitute the first stage of the decision‐making process. In turn, choices are made in the second stage concerning the choice of particular activities (hospital versus office care, for example) or procedures (ordinary versus complete medical examinations), given the total medical care activity chosen in the first stage.

The objective of the study is to identify physicians' responses to exogenous shocks in the remuneration system. The focus of analysis is shifted away from the identification of Supply‐Induced Demand (SID) to a more pragmatic analysis of some of the determinants of physicians' choices. The study uses monthly activity data on a panel of 677 Québec GPs between 1977 and 1983. Quantity adjustments and drifts to more complex (and therefore better paid) procedures are evidenced, mainly in response to a fifteen month tariff‐freeze. Physicians' ability to control their own work loads is also documented, both in terms of timing and level of complexity, and expenditure caps (in the form of an individual ceiling on GPs' quarterly gross income) are found to be effective at curbing high activity rates.
Capitation payments based on prior hospitalizations
Authors: Van Vliet R. C. J. A. , van de Ven W. P. M. M.
Published: May 2007

In many countries the concept of capitating health care insurers is receiving increasing attention. In a competitive environment, capitation should induce insurers to concentrate more on cost containment instead of indulging in risk selection. The necessary premium‐replacing capitation payments should account for predictable variations in annual per‐person health care expenditures as far as these are related to health status. Various studies have shown that crude capitation models based on e.g. age, sex and place of residence, do not reflect expected costs accurately. This implies inefficient pricing possibly leading to risk selection and windfall profits or losses for insurers, thereby undermining the objectives of a capitation system.

Using Dutch micro data on some 200,000 individuals, this article simulates various alternative capitation models based on, among others, diagnostic information from previous hospitalizations. Results suggest that the problems of both risk selection and windfall profits/losses may be mitigated substantially by using this type of information together with data on prior costs. These results are not only relevant for situations where competing insurers are capitated, as intended in the Netherlands, but also when providers are capitated, as in the UK, or when HMOs are capitated, as in the US.
The demand for health: An empirical reformulation of the Grossman model
Authors: Wagstaff Adam
Published: May 2007

Previous tests of Grossman's model of the demand for health have been based on Grossman's own empirical formulation. This paper argues that this formulation fails to capture the dynamic character of the model. It proposes an alternative formulation, which appears to be more consistent with Grossman's theoretical model and which may also explain the apparent rejections of the model by the data in the author's earlier empirical work. The paper also presents some empirical results obtained using the new formulation, which are, on the whole, consistent with the predictions of Grossman's theoretical model.
Clinical importance, statistical significance and the assessment of economic and quality‐of‐life outcomes
Authors: Drummond Michael , O'Brienm Bernie
Published: May 2007

The assessment of economic and quality‐of‐life outcomes of health care interventions is moving into a new era, with such assessments increasingly being made within the context of controlled clinical trials. Traditionally the measurement of many variables in economic evaluations, particularly costs, has been deterministic. In the context of clinical trials the measurement of variables is stochastic, with the standard principles of statistical inference being applied to analyse differences between treatments in terms of effectiveness. Economists participating in clinical research are therefore being called upon to specify the sample size for the economic component of the evaluation and to undertake statistical tests for differences in cost or cost‐effectiveness. This paper discusses the current methodological issues surrounding stochastic measurement in clinical trials, discusses the additional issues raised by the assessment of economic and quality‐of‐life outcomes and specifies the challenges facing economists if they are to answer the questions now being posed about economic analysis by statisticians and clinical researchers. It is concluded that application of the standard principles of statistical inference to economic data is not straightforward and will require value judgements to be made about statistical significance and economic importance, which may differ from those already made in purely clinical studies.
The rand 36‐item health survey 1.0
Authors: Hays Ron D. , Sherbourne Cathy Donald , Mazel Rebecca M.
Published: May 2007

Recently, Ware and Sherbourne1 published a new short‐form health survey, the MOS 36‐Item Short‐Form Health Survey (SF‐36), consisting of 36 items included in long‐form measures developed for the Medical Outcomes Study. The SF‐36 taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, general mental health, social functioning, energy/fatigue, and general health perceptions. It also includes a single item that provides an indication of perceived change in health. The SF‐36 items and scoring rules are distributed by MOS Trust, Inc. Strict adherence to item wording and scoring recommendations is required in order to use the SF‐36 trademark. The RAND 36‐Item Health Survey 1.0 (distributed by RAND) includes the same items as those in the SF‐36, but the recommended scoring algorithm is somewhat different from that of the SF‐36. Scoring differences are discussed here and new T‐scores are presented for the 8 multi‐item scales and two factor analytically‐derived physical and mental health composite scores.
The costs and effects of open versus laparoscopic cholecystectomies
Authors: Kesteloot K. , Penninckx F.
Published: May 2007

The costs and effects of open versus laparoscopic cholecystectomies are compared, from the point of view of hospitals and patients, for a consecutive series of 47 patients undergoing a cholecystectomy in the University Hospital Gasthuisberg, in Belgium.

For the patients the laparoscopic technique is superior, since effects are better and direct costs are lower than for the open technique.

From a financial viewpoint, hospitals have to weigh the higher costs of the laparoscopic equipment against the lower variable costs due to the shorter postoperative length of stay. Total hospital costs would be lower in case all cholecystectomies were performed with the laparoscopic rather than with the open technique if at least 140 cholecystectomies are done annually with the electrocautery technique, or 300 procedures with laser.

However, more recent data reveal that the operating time reduces with the number of laparoscopic procedures (learning effects), implying that the laparoscopic electrocautery procedure would already be the cheaper alternative if more than 70 cholecystectomies are done annually, if disposables are used (or if 50 procedures are done with re‐usables).

It can be concluded that, once sufficient experience with laparoscopy has been achieved, most hospitals could realise cost savings by switching, as much as is medically justified, to laparoscopic procedures. This will also hold for hospitals performing few cholecystectomies, as long as re‐usables and electrocautery are used.
Cost‐benefit analysis of a national screening programme for cystic fibrosis in an israeli population
Authors: Ginsberg Gary , Blau Hannah , Kerem Eitan , Springer Chaim , Kerem Bat‐Sheba , Akstein Edna , Greenberg Alan , Kolumbos Ami , Abeliovich Devorah , Gazit Eli , Yahav Jacob
Published: May 2007

The recently acquired ability to identify 97% of CF carriers in an Israeli Ashkenazi population, prompts an evaluation of a nationwide screening programme. In 1993, the programme would first screen and counsel 9,261 parents, then 396 spouses of carrier parents and finally screen 16.5 fetuses where both parents are carriers. Assuming 92% of screened parents choose abortion of fetus screened positive, 2.33 cases of CF will be prevented in 1993 at a direct cost of $781,000. The $326,000 direct costs of preventing a CF case, exceed the lifetime excess direct costs per case of $297,000. However, benefits of screening also accrue to subsequent pregnancies, resulting in a direct benefit ($14.45 million) to cost ($10.39 million) ratio of 1.39/1 for the period 1993–2032. When benefits and costs resulting from mortality changes, work absences and transport costs are included, the benefit ($15.95 million) to cost ($13.88 million) ratio falls to 1.15/1. Benefit‐cost ratios are lower for other ethnic groups in Israel, due to lower carrier rates and lower mutation detection abilities. A CF screening programme will increase the freedom of individuals choice, but should be carried out carefully in order to minimize stigmatization and even discrimination against CF carriers.