Optimal priming of poxvirus vector (NYVAC)-based HIV vaccine regimens requires 3 DNA injections. Results of the EV03/ANRS Vac20 Phase I/II Trial

Background: Two or three DNA primes have been used in previous smaller clinical trials, but the number required for optimal priming of viral vectors has never been assessed in adequately powered clinical trials. The EV03/ANRS Vac20 phase I/II trial investigated this issue using the DNA prime/poxvirus NYVAC boost combination, both expressing a common HIV-1 clade C immunogen consisting of Env and Gag-Pol-Nef polypeptide. Methods: 147 healthy volunteers were randomly allocated through 8 European centres to either 3xDNA plus 1xNYVAC (weeks 0, 4, 8 plus 24; n¼74) or to 2xDNA plus 2xNYVAC (weeks 0, 4 plus 20, 24; n¼73), stratified by geographical region and sex. T cell responses were quantified using the interferon g Elispot assay and 8 peptide pools; samples from weeks 0, 26 and 28 (time points for primary immunogenicity endpoint), 48 and 72 were considered for this analysis. Results: 140 of 147 participants were evaluable at weeks 26 and/ or 28. 64/70 (91%) in the 3xDNA arm compared to 56/70 (80%) in the 2xDNA arm developed a T cell response (P¼0.053). 26 (37%) participants of the 3xDNA arm developed a broader T cell response (Env plus at least to one of the Gag, Pol, Nef peptide pools) versus 15 (22%) in the 2xDNA arm (P¼0.047). At week 26, the overall magnitude of responses was also higher in the 3xDNA than in the 2xDNA arm (similar at week 28), with a median of 545 versus 328 SFUs/106 cells at week 26 (P<0.001). Preliminary overall evaluation showed that participants still developed T-cell response at weeks 48 (78%, n¼67) and 72 (70%, n¼66). Conclusion: This large clinical trial demonstrates that optimal priming of poxvirus-based vaccine regimens requires 3 DNA regimens and further confirms that the DNA/NYVAC prime boost vaccine combination is highly immunogenic and induced durable T-cell responses.

Stability of the Helical TomoTherapy Hi·Art II detector for treatment beam irradiations.

The Hi·Art II Helical TomoTherapy (HT) unit is equipped with a built-in onboard MVCT detector used for patient imaging and beam monitoring. Our aim was to study the detector stability for treatment beam measurements. We studied the MVCT detector response with the 6 MV photon beam over time, throughout short-term (during an irradiation) and long-term (two times 50 days) periods. Our results show a coefficient of variation ≤ 1% for detector chambers inside the beam (excluding beam gradients) for short- and long-term response of the MVCT detector. Larger variations were observed in beam gradients and an influence of the X-ray target where degradation was found. The results assume that an 'air scan' procedure is performed daily to recalibrate the detector with the imaging beam. On short term, the detector response stability is comparable to other devices. Long-term measure- ments during two 50-day periods show a good reproducibility. 

Psychodynamic interventions in cancer care II: a qualitative analysis of the therapists' reports.

BACKGROUND: To investigate the focus of psychodynamic-oriented interventions in cancer patients by means of a qualitative analysis of the therapists' reports. METHODS: One hundred thirty-five reports collected within a controlled psychotherapy trial were analyzed; the themes addressed during the intervention were classified in categories reflecting the focus of the intervention and correlated with sociodemographic and medical data and type of intervention. RESULTS: Twenty main themes were identified and classified in two categories: category 1 corresponded to interventions based on expression and support, and category 2 to interventions based on introspection, with subcategory 2.1 focusing on the patient's psychological functioning and subcategory 2.2 focusing on his way to engage and communicate in relationships. While the most frequently addressed theme was related to the diagnosis of cancer (N = 102/576; 22.6%), the majority of themes were related to other concerns (N = 446/576; 77.4%). Half of the interventions (50.4%) were classified in category 1, 27.4% in category 2.1, and 9.6% in category 2.2. Patients of category 1 entered less often brief psychotherapy (step 2 of the intervention) and more frequently suffered from advances disease. CONCLUSIONS: A wide variety of themes are addressed in psychodynamic interventions in the oncology setting, illustrating that cancer is not the only focus of therapy. Other themes reflect different psychological difficulties triggered by the disease. This study illustrates that cancer patients have different needs, which surpass the event of the disease. Early clarification and comprehension of the demand may therefore be beneficial to adjust the therapeutic approach. Copyright © 2013 John Wiley & Sons, Ltd.

Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial SAKK17/04.

Aim: We have previously documented the feasibility of neoadjuvant chemotherapy and EPP in a multicenter trial of MPM (Weder, Ann Oncol 18: 1196, 2007). The objectives of the trimodality trial SAKK17/04 (NCT00334594) were to evaluate the time to loco-regional relapse with or without high dose hemithoracic radiotherapy in a prospective multicenter randomized phase II trial in patients with R0 and R1 resection after neoadjuvant chemotherapy and EPP. Methods: Eligible patients had pathologically confirmed MPM, surgically resectable TNM stage (T1-3 N0-2 M0), PS0-1, ages 18-70 years. Part 1 had a phase II design, and included neoadjuvant chemotherapy with 3 cycles of cisplatin and pemetrexed, followed by restaging and EPP. The primary endpoint of part 1 was complete macroscopic resection (R0-1). Part 2 randomized consenting patients with R0-1 resection into two parallel phase II arms (control arm A and radiotherapy arm B). The primary endpoint for part 2 was loco-regional relapse-free survival (RFS). To detect a 1 year increase with 80% power and 10% alpha, 37 patients were needed for arm B. Secondary endpoints included operability, tolerability of chemotherapy and radiotherapy, survival, and translational research Results: Because accrual of part 2 was slower than planned, the trial was stopped in 2013. Overall, 153 patients entered the trial, of whom 125 underwent surgery and 99 had a complete macroscopic resection (primary endpoint part 1). Of the later patients, 54 could be randomized 1:1 into each arm. Reasons for non-randomization included patient refusal in 24 and ineligibility or protocol deviations in 21. Of the 27 patients randomized to hemithoracic radiotherapy, 25 completed the treatment as planned. For part 1 the median RFS was 8.8 (95%CI: 7.3-10.7) and median OS was 15.0 (95% CI: 12.1-19.3) months. For part 2 the median local RFS for group A was 7.6 (95%CI: 5.5-10.7) and for group B 9.4 (95%CI: 6.5-11.9) months (primary endpoint part 2), while the overall RFS and OS for group A were 5.7 (95%CI: 3.5-8.8) and 16.9 (95%CI: 10.7-23.6) months and for group B 7.6 (95% CI:5.2-10.6) and 14.9 (95%CI: 7.0-17.6) months. Conclusions: This study did not reach the primary endpoint which was defined as one-year increase in loco-regional relapse-free survival and thus does not support the routine use of hemithoracic RT after neoadjuvant chemotherapy and EPP. Disclosure: All authors have declared no conflicts of interest.

Genomic analysis of the blood attributed to Louis XVI (1754-1793), king of France.

A pyrographically decorated gourd, dated to the French Revolution period, has been alleged to contain a handkerchief dipped into the blood of the French king Louis XVI (1754-1793) after his beheading but recent analyses of living males from two Bourbon branches cast doubts on its authenticity. We sequenced the complete genome of the DNA contained in the gourd at low coverage (similar to 2.5x) with coding sequences enriched at a higher similar to 7.3x coverage. We found that the ancestry of the gourd's genome does not seem compatible with Louis XVI's known ancestry. From a functional perspective, we did not find an excess of alleles contributing to height despite being described as the tallest person in Court. In addition, the eye colour prediction supported brown eyes, while Louis XVI had blue eyes. This is the first draft genome generated from a person who lived in a recent historical period; however, our results suggest that this sample may not correspond to the alleged king.

POPULATION STRUCTURE AND SPATIAL DISTRIBUTION OF Bauhinia cheilantha (Bong.) Steud. IN TWO FRAGMENTS AT DIFFERENT REGENERATION STAGES IN THE CAATINGA, IN SERGIPE, BRAZIL

ABSTRACTThis study aimed to analyze the vertical and diameter structure and the spatial distribution pattern of Bauhinia cheilantha in two Caatinga fragments in Sergipe, Brazil, at different regeneration stages. Thirty plots were demarcated in area I (Canindé de São Francisco and Poço Redondo), which has vegetation regeneration, and 25 plots in area II (Porto da Folha) with preserved vegetation, both having 400 m2. All B. cheilanthaindividuals had their height and circumference (circumference at breast height > 6 cm) measured. Possible differences in height and diameter at breast height were tested in the two populations by using Student’s T-test. The distribution pattern of species was calculated through Payandeh’s index. We sampled 154 B. cheilantha individuals, equivalent to 33.3% of the plots in area I and in 1,027 individuals in area II, totaling 100% frequency. Height and the diameter of the two populations were statistically different, where AI achieved all values lower than AII. The spatial distribution pattern of B. cheilantha found in both areas was aggregate, with values of 11.85 and 9.00, respectively. Thus, it became clear that the population in AII is at a more advanced successional status than AI, due to its longer conservation time.

A Study of African American Vernacular English in Three Novels and Colloquial Finnish in their Translations – The Dark Tower II: The Drawing of the Three, A Time to Kill and Push

Pro gradu -tutkielma käsittelee afroamerikkalaisen puhekielen (African American Vernacular English, AAVE) käyttöä kolmen englanninkielisen romaanin dialogissa ja suomen yleispuhekielen käyttöä romaanien käännöksissä. Tutkimus on pääasiassa kvantitatiivinen ja deskriptiivinen. Romaanit ovat Stephen Kingin The Dark Tower II: The Drawing of the Three (1987) (Musta torni 2, Kolme korttia pakasta 2005, suom. Kari Salminen), John Grishamin A Time to Kill (1989) (On aika tappaa 1994, suom. Kimmo Linkama) ja Sapphiren Push (1996) (Precious – harlemilaistytön tarina 2010, suom. Kristiina Drews). Alkukielisten romaanien osalta Grisham ja Sapphire suosivat lauseopillisia kielenpiirteitä, kun taas King on suosinut äänteellisiä. Sen sijaan käännöksissä piirteistä yleisimpiä ovat äänteelliset ja harvinaisimpia lauseopilliset. Vaikka käännöksissä sanastolliset piirteet ovat taajaan esiintyviä, äänteellisiä piirteitä esiintyy niitä enemmän. Poikkeuksena on On aika tappaa, jossa sanastollisia piirteitä esiintyy enemmän kuin äänteellisiä. Tulos eroaa Sampo Nevalaisen vuonna 2003 tekemästä tutkimuksesta, jossa hän sai selville, että käännöksissä käytetyt piirteet olivat enimmäkseen sanastollisia, kun taas alun perin suomeksi kirjoitetussa kaunokirjallisuudessa puhekielisyyden vaikutelma saatiin aikaan pääasiassa äänteellisin keinoin. Mahdollinen selitys tässä tutkimuksessa havaitulle erolle on se, että kahdessa romaanissa esiintyvä leimallinen AAVEn käyttö on saanut kääntäjät käyttämään samanlaisia strategioita kuin suomalaiset kirjailijat murretta kirjoittaessaan.

Distribution of the human leukocyte antigen class II alleles in Brazilian patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55% of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1%) and HLA-DQB1*02 (52.9 vs 38.7%) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0%) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1%) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.

An investigation into the functional role of the D1:1 and D1:2 polypeptides in photosystem II in cyanobacteria : the effect of changing PSI/PSII ratio on photoinhibition in Synechococcus sp. PCC7942 /

The cyanobacterium Synechococcus sp. PCC 7942 (Anacystis nidulans R2) adjusts its photosynthetic function by changing one of the polypeptides of photosystem II. This polypeptide, called Dl, is found in two forms in Synechococcus sp. PCC 7942. Changing the growth light conditions by increasing the light intensity to higher levels results in replacement of the original form of D 1 polypeptide, D 1: 1, with another form, D 1 :2. We investigated the role of these two polypeptides in two mutant strains, R2S2C3 (only Dl:l present) and R2Kl (only Dl:2 present) In cells with either high or low PSI/PSII. R2S2C3 cells had a lower amplitude for 77 K fluorescence emission at 695 nm than R2Kl cells. Picosecond fluorescence decay kinetics showed that R2S2C3 cells had shorter lifetimes than R2Kl cells. The lower yields and shorter lifetimes observed in the D 1 and Dl:2 containing cells. containing cells suggest that the presence of D 1: 1 results in more photochemical or non-photochemical quenching of excitation energy In PSII. One of the most likely mechanisms for the increased quenching in R2S2C3 cells could be an increased efficiency in the transfer of excitation energy from PSII to PSI. However, photophysical studies including 77 K fluorescence measurements and picosecond time resolved decay kinetics comparing low and high PSI/PSII cells did not support the hypothesis that D 1: 1 facilitates the dissipation of excess energy by energy transfer from PSII to PSI. In addition physiological studies of oxygen evolution measurements after photoinhibition treatments showed that the two mutant cells had no difference in their susceptibility to photoinhibition with either high PSI/PSII ratio or low PSI/PSII ratio. Again suggesting that, the energy transfer efficiency from PSII to PSI is likely not a factor in the differences between Dl:l and Dl:2 containing cells.

Isolation and partial characterization of a complementary protein from the mycoparasite, Piptocephalis virginiana, which specifically binds to two glycoproteins b and c of the host cell surface

Presence of surface glycoprotein in Piptocephalis virginiana that recognizes the host glycoproteins band c, reported earlier from our laboratory, was detected by immunofluorescence microscopy. Germinated spores of P. virginiana treated with Mortierella pusilla cell wall protein extract, primary antibodies prepared against glycoproteins band c and FITC-goat anti-rabbit IgG conjugate showed fluorescence. This indicated that on the surfaces of the biotrophic mycoparasite P. virginiana , there might be a complementary molecule which recognizes the glycoproteins band c from M. pusilla. Immunobinding analysis identified a glycoprotein of Mr 100 kDa from the mycoparasite which binds with the host glycoproteins band c, separately as well as collectively. Purification of this glycoprotein was achieved by (i) 60% ammonium sulfate precipitation, (ii) followed by heat treatment, and (iii) Sephadex G-IOO gel filtration. The glycoprotein was isolated by preparative polyacrylamide gel electrophoresis by cutting and elution. The purity of the protein ·was ascertained by SDS-PAGE and Western blot analysis. Positive reaction to periodic acid-Schiff reagent revealed the glycoprotein nature of this 100 kDa protein. Mannose was identified as a major sugar component of this glycoprotein by using a BoehringerMannheim Glycan Differentiation Kit. Electrophoretically purified glycoprotein was used to raIse polyclonal antibody in rabbit. The specificity of the antibody was determined by dot-immunobinding test and western-blot analysis. Immunofluorescence mIcroscopy revealed surface localization of the protein on the germ tube of Piptocephalis virginiana. Fluorescence was also observed at the surfaceJ of the germinated spores and hyphae of the host, M. pusilla after treatment with complementary protein from P. virginiana, primary antibody prepared against the complementary protein and FITC-goat anti-rabbit IgG conjugate.

Optimizing Computational Frameworks to Study the Influence of the Protein Environment on the Individual Site Energies of Chromophores in Photosystem II of Photosynthesis

Photosynthesis is a process in which electromagnetic radiation is converted into chemical energy. Photosystems capture photons with chromophores and transfer their energy to reaction centers using chromophores as a medium. In the reaction center, the excitation energy is used to perform chemical reactions. Knowledge of chromophore site energies is crucial to the understanding of excitation energy transfer pathways in photosystems and the ability to compute the site energies in a fast and accurate manner is mandatory for investigating how protein dynamics ef-fect the site energies and ultimately energy pathways with time. In this work we developed two software frameworks designed to optimize the calculations of chro-mophore site energies within a protein environment. The first is for performing quantum mechanical energy optimizations on molecules and the second is for com-puting site energies of chromophores in a fast and accurate manner using the polar-izability embedding method. The two frameworks allow for the fast and accurate calculation of chromophore site energies within proteins, ultimately allowing for the effect of protein dynamics on energy pathways to be studied. We use these frame-works to compute the site energies of the eight chromophores in the reaction center of photosystem II (PSII) using a 1.9 Å resolution x-ray structure of photosystem II. We compare our results to conflicting experimental data obtained from both isolat-ed intact PSII core preparations and the minimal reaction center preparation of PSII, and find our work more supportive of the former.

High-Spin and Emissive Molecular Materials: Synthesis and Characterization of New Polynuclear Ni(II) Complexes from the Use of Aromatic Schiff Bases as Bridging Ligands

The employment of the bridging/chelating Schiff bases, N-salicylidene-4-methyl-o-aminophenol (samphH2) and N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in nickel cluster chemistry has afforded eight polynuclear Ni(II) complexes with new structural motifs, interesting magnetic and optical properties, and unexpected organic ligand transformations. In the present thesis, Chapter 1 deals with all the fundamental aspects of polynuclear metal complexes, molecular magnetism and optics, while research results are reported in Chapters 2 and 3. In the first project (Chapter 2), I investigated the coordination chemistry of the organic chelating/bridging ligand, N-salicylidene-4-methyl-o-aminophenol (samphH2). The general NiII/tBuCO2-/samphH2 reaction system afforded two new tetranuclear NiII clusters, namely [Ni4(samph)4(EtOH)4] (1) and [Ni4(samph)4(DMF)2] (2), with different structural motifs. Complex 1 possessed a cubane core while in complex 2 the four NiII ions were located at the four vertices of a defective dicubane. The nature of the organic solvent was found to be of pivotal importance, leading to compounds with the same nuclearity, but different structural topologies and magnetic properties. The second project, the results of which are summarized in Chapter 3, included the systematic study of a new optically-active Schiff base ligand, N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH2), in NiII cluster chemistry. Various reactions between NiX2 (X- = inorganic anions) and nacbH2 were performed under basic conditions to yield six new polynuclear NiII complexes, namely (NHEt3)[Ni12(nacb)12(H2O)4](ClO4) (3), (NHEt3)2[Ni5(nacb)4(L)(LH)2(MeOH)] (4), [Ni5(OH)2(nacb)4(DMF)4] (5), [Ni5(OMe)Cl(nacb)4(MeOH)3(MeCN)] (6), (NHEt3)2[Ni6(OH)2(nacb)6(H2O)4] (7), and [Ni6(nacb)6(H2O)3(MeOH)6] (8). The nature of the solvent, the inorganic anion, X-, and the organic base were all found to be of critical importance, leading to products with different structural topologies and nuclearities (i.e., {Ni5}, {Ni6} and {Ni12}). Magnetic studies on all synthesized complexes revealed an overall ferromagnetic behavior for complexes 4 and 8, with the remaining complexes being dominated by antiferromagnetic exchange interactions. In order to assess the optical efficiency of the organic ligand when bound to the metal centers, photoluminescence studies were performed on all synthesized compounds. Complexes 4 and 5 show strong emission in the visible region of the electromagnetic spectrum. Finally, the ligand nacbH2 allowed for some unexpected organic transformations to occur; for instance, the pentanuclear compound 5 comprises both nacb2- groups and a new organic chelate, namely the anion of 5-chloro-2-[(3-hydroxy-4-oxo-1,4-dihydronaphthalen-1-yl)amino]benzoic acid. In the last section of this thesis, an attempt to compare the NiII cluster chemistry of the N-naphthalidene-2-amino-5-chlorobenzoic acid ligand with that of the structurally similar but less bulky, N-salicylidene-2-amino-5-chlorobenzoic acid (sacbH2), was made.

Three works on religious themes : psalmus 150, string quartet on the life of Saint John Paul II and symphony “The Redemption”

Dans cette dissertation, je présente trois pièces sur des thèmes religieux composées au cours de ma maîtrise, ainsi que leur analyse : Psalmus 150 pour chœur de jeunes à trois voix, chœur d'adultes à huit voix et orgue ou piano ; Quatuor à Cordes sur la vie de Saint Jean-Paul II ; et la Symphonie « La Rédemption » pour orchestre et chœur. Malgré les particularités de chacune, elles présentent des aspects communs. L'idée principale des compositions fut d'éviter la rupture avec la tradition tout en apportant des nouvelles idées aux pièces, et de souligner l'importance de ma recherche sur la beauté. À cet égard, certaines techniques contemporaines, ainsi que les sonorités médiévales des quintes et octaves parallèles, furent utilisées en accord avec un langage tonal / modal qui demeure la base des trois compositions. Le chant Grégorien fut aussi une importante caractéristique de ces compositions. Pour mieux comprendre les analyses des œuvres, deux techniques seront expliquées, la douce toile de dissonances linéaires et l'harmonie d'accords parfaits majeurs. L'analyse de chaque pièce est divisée en deux parties. La première est une vision générale et la deuxième est plus détaillée. À la fin, les connaissances acquises par la composition des ces œuvres seront résumées et l'importance intemporelle de la beauté sera réaffirmée.

Analysis of the electronic structure, hyperfine structure, and volume isotope shifts in the low lying states of BA I and BA II

Relativistic multi-configuration Dirac Fock (MCDF) wavefunctions coupled to good angular momentum J have been calculated for low lying states of Ba I and Ba II. These wavefunctions are compared with semiempirical ones derived from experimental atomic energy levels. It is found that significantly better agreement is obtained when close configurations are included in the MCDF wavefunctions. Calculations of the electronic part of the field isotope shift lead to very good agreement with electronic factors derived from experimental data. Furthermore, the slopes of the lines in a King plot analysis of many of the optical lines are predicted accurately by these calculations. However, the MCDF wavefunctions seem not to be of sufficient accuracy to give agreement with the experimental magnetic dipole and electric quadrupole hyperfine structure constants.

The physical properties of the atmosphere in the new Hadley Centre Global Environmental Model (HadGEM1). Part II: Aspects of variability and regional climate

The performance of the atmospheric component of the new Hadley Centre Global Environmental Model (HadGEM1) is assessed in terms of its ability to represent a selection of key aspects of variability in the Tropics and extratropics. These include midlatitude storm tracks and blocking activity, synoptic variability over Europe, and the North Atlantic Oscillation together with tropical convection, the Madden-Julian oscillation, and the Asian summer monsoon. Comparisons with the previous model, the Third Hadley Centre Coupled Ocean-Atmosphere GCM (HadCM3), demonstrate that there has been a considerable increase in the transient eddy kinetic energy (EKE), bringing HadGEM1 into closer agreement with current reanalyses. This increase in EKE results from the increased horizontal resolution and, in combination with the improved physical parameterizations, leads to improvements in the representation of Northern Hemisphere storm tracks and blocking. The simulation of synoptic weather regimes over Europe is also greatly improved compared to HadCM3, again due to both increased resolution and other model developments. The variability of convection in the equatorial region is generally stronger and closer to observations than in HadCM3. There is, however, still limited convective variance coincident with several of the observed equatorial wave modes. Simulation of the Madden-Julian oscillation is improved in HadGEM1: both the activity and interannual variability are increased and the eastward propagation, although slower than observed, is much better simulated. While some aspects of the climatology of the Asian summer monsoon are improved in HadGEM1, the upper-level winds are too weak and the simulation of precipitation deteriorates. The dominant modes of monsoon interannual variability are similar in the two models, although in HadCM3 this is linked to SST forcing, while in HadGEM1 internal variability dominates. Overall, analysis of the phenomena considered here indicates that HadGEM1 performs well and, in many important respects, improves upon HadCM3. Together with the improved representation of the mean climate, this improvement in the simulation of atmospheric variability suggests that HadGEM1 provides a sound basis for future studies of climate and climate change.