Characterization of intonation in Karṇāṭaka music by parametrizing context-based Svara Distributions

Intonation is a fundamental music concept that has a special relevance in Indian art music. It is characteristic of the rāga and intrinsic to the musical expression of the performer. Describing intonation is of importance to several information retrieval tasks like the development of rāga and artist similarity measures. In our previous work, we proposed a compact representation of intonation based on the parametrization of the pitch histogram of a performance and demonstrated the usefulness of this representation through an explorative rāga recognition task in which we classified 42 vocal performances belonging to 3 rāgas using parameters of a single svara. In this paper, we extend this representation to employ context-based svara distributions, which are obtained with a different approach to find the pitches belonging to each svara. We quantitatively compare this method to our previous one, discuss the advantages, and the necessary melodic analysis to be carried out in future.

Blood pressure normalization in a large population of hypertensive patients treated with perindopril/indapamide combination: results of the OPTIMAX trial.

OBJECTIVE: To determine if the fixed-dose perindopril/indapamide combination (Per/Ind) normalizes blood pressure (BP) in the same fraction of hypertensive patients when treated in everyday practice or in controlled trials. METHODS: In this prospective trial, 17 938 hypertensive patients were treated with Per 2 mg/Ind 0.625 mg for 3-6 months. In Group 1 Per/Ind was initiated in newly diagnosed patients (n = 7032); in Group 2 Per/Ind replaced previous therapy in patients already treated but having either their BP still uncontrolled or experiencing side-effects (n = 7423); in Group 3 Per/Ind was added to previous treatment in patients with persistently high BP (n = 3483). BP was considered normalized when < or = 140/90 mm Hg. A multivariate analysis for predictors of BP normalization was performed. RESULTS: Subjects were on average 62 years old and had a baseline BP of 162.3/93.6 mm Hg. After treatment with Per/Ind, BP normalization was reached in 69.6% of patients in the Initiation group, 67.5% in the Replacement Group, and 67.4% in the Add-on Group (where patients were more frequently at risk, diabetic, or with target organ damage). Mean decreases in systolic BP of 22.8 mm Hg and in diastolic BP of 12.4 mm Hg were recorded. CONCLUSIONS: This trial was established to reflect everyday clinical practice, and a treatment strategy based on the Per/Ind combination, administered as initial, replacement, or add-on therapy, led to normalization rates that were superior to those observed in Europe in routine practice. These results support recent hypertension guidelines which encourage the use of combination therapy in the management of arterial hypertension.

Multiple Paternity in Polyandrous Barn Owls (Tyto alba).

In polyandrous species females produce successive clutches with several males. Female barn owls (Tyto alba) often desert their offspring and mate to produce a 2(nd) annual brood with a second male. We tested whether copulating during chick rearing at the 1(st) annual brood increases the male's likelihood to obtain paternity at the 2(nd) annual breeding attempt of his female mate in case she deserts their brood to produce a second brood with a different male. Using molecular paternity analyses we found that 2 out of 26 (8%) second annual broods of deserting females contained in total 6 extra-pair young out of 15 nestlings. These young were all sired by the male with whom the female had produced the 1(st) annual brood. In contrast, none of the 49 1(st) annual breeding attempts (219 offspring) and of the 20 2(nd) annual breeding attempts (93 offspring) of non-deserting females contained extra-pair young. We suggest that female desertion can select male counter-strategies to increase paternity and hence individual fitness. Alternatively, females may copulate with the 1(st) male to derive genetic benefits, since he is usually of higher quality than the 2(nd) male which is commonly a yearling individual.

Synchronous and baroceptor-sensitive oscillations in skin microcirculation: evidence for central autonomic control.

To determine whether skin blood flow is local or takes part in general regulatory mechanisms, we recorded laser-Doppler flowmetry (LDF; left and right index fingers), blood pressure, muscle sympathetic nerve activity (MSNA), R-R interval, and respiration in 10 healthy volunteers and 3 subjects after sympathectomy. We evaluated 1) the synchronism of LDF fluctuations in two index fingers, 2) the relationship with autonomically mediated fluctuations in other signals, and 3) the LDF ability to respond to arterial baroreflex stimulation (by neck suction at frequencies from 0.02 to 0.20 Hz), using spectral analysis (autoregressive uni- and bivariate, time-variant algorithms). Synchronous LDF fluctuations were observed in the index fingers of healthy subjects but not in sympathectomized patients. LDF fluctuations were coherent with those obtained for blood pressure, MSNA, and R-R interval. LDF fluctuations were leading blood pressure in the low-frequency (LF; 0.1 Hz) band and lagging in the respiratory, high-frequency (HF; approximately 0.25 Hz) band, suggesting passive "downstream" transmission only for HF and "upstream" transmission for LF from the microvessels. LDF fluctuations were responsive to sinusoidal neck suction up to 0.1 Hz, indicating response to sympathetic modulation. Skin blood flow thus reflects modifications determined by autonomic activity, detectable by frequency analysis of spontaneous fluctuations.

Hand development and sequence of ossification in the forelimb of the European shrew Crocidura russula (Soricidae) and comparisons across therian mammals.

Hand development in the European shrew Crocidura russula is described, based on the examination of a cleared and double-stained ontogenetic series and histological sections of a c. 20-day-old embryo and a neonate. In the embryo all carpal elements are still mesenchymal condensations, and there are three more elements than in the adult stage: the 'lunatum', which fuses with the scaphoid around birth; a centrale, which either fuses with another carpal element or just disappears later in ontogeny; and the anlage of an element that later fuses with the radius. Carpal arrangement in the neonate and the adult is the same. In order to compare the relative timing of the onset of ossification in forelimb bones in C. russula with that of other therians, we built up two matrices of events based on two sets of data and used the event-pair method. In the first analysis, ossification of forelimb elements in general was examined, including that of the humerus, radius, ulna, the first carpal and metacarpal to ossify, and the phalanges of the third digit. The second analysis included each carpal, humerus, radius, ulna, the first metacarpal and the first phalanx to ossify. Some characters (= event-pairs) provide synapomorphies for some clades examined. There have been some shifts in the timing of ossification apparently not caused by ecological and/or environmental influences. In two species (Oryctolagus and Myotis), there is a tendency to start the ossification of the carpals relatively earlier than in all other species examined, the sauropsid outgroups included.

Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma.

BACKGROUND & AIMS: Pazopanib has demonstrated clinical benefit in patients with advanced renal cell carcinoma (RCC) and is generally well tolerated. However, transaminase elevations have commonly been observed. This 2-stage study sought to identify genetic determinants of alanine transaminase (ALT) elevations in pazopanib-treated white patients with RCC.¦METHODS: Data from two separate clinical studies were used to examine the association of genetic polymorphisms with maximum on-treatment ALT levels.¦RESULTS: Of 6852 polymorphisms in 282 candidate genes examined in an exploratory dataset of 115 patients, 92 polymorphisms in 40 genes were significantly associated with ALT elevation (p<0.01). Two markers (rs2858996 and rs707889) in the HFE gene, which are not yet known to be associated with hemochromatosis, showed evidence for replication. Because of multiple comparisons, there was a 12% likelihood the replication occurred by chance. These two markers demonstrated strong linkage disequilibrium (r(2)=0.99). In the combined dataset, median (25-75th percentile) maximum ALT values were 1.2 (0.7-1.9), 1.1 (0.8-2.5), and 5.4 (1.9-7.6)×ULN for rs2858996 GG (n=148), GT (n=82), and TT (n=1 2) genotypes, respectively. All 12 TT patients had a maximum ALT>ULN, and 8 (67%) had ALT≥3×ULN. The odds ratio (95% CI) for ALT≥3×ULN for TT genotype was 39.7 (2.2-703.7) compared with other genotypes. As a predictor of ALT≥3×ULN, the TT genotype had a negative predictive value of 0.83 and positive predictive value of 0.67. No TT patients developed liver failure.¦CONCLUSIONS: The rs2858996/rs707889 polymorphisms in the HFE gene may be associated with reversible ALT elevation in pazo-panib-treated patients with RCC.

Markedly reduced blood pressure responsiveness in endotoxemic rats; reversal by neuropeptide Y.

This study in conscious normotensive rats was performed to assess the effect of the vasoconstrictor peptide, neuropeptide Y (NPY), on blood pressure responsiveness to exogenous norepinephrine in endotoxaemia. NPY and endotoxin were infused at doses which had no effect on blood pressure, whether given alone or in combination. Endotoxin markedly reduced the pressor responses to bolus injections of norepinephrine. However, blood pressure responsiveness could be enhanced by infusing NPY simultaneously with the endotoxin. It is suggested that low dose NPY infusions may be clinically useful in reversing the reduced vascular responsiveness to pressor amines in shock.

Psychometric properties of the french translation of the constructive thinking inventory in a sample of adolescents and young adults

The Constructive Thinking Inventory (CTI) measures cognitive coping strategies used in everyday problem solving. The main objective of this study was to assess the factorial structure, the internal consistency, the correspondence with the American normative values, and the discriminant validity of the French translation. A community sample of 777 students aged 12 to 26 years, recruited from schools, colleges and universities, answered the 108item selfreport CTI questionnaire during a class period. A sample of 60 male adolescent offenders aged 13 to 18 years, recruited from two institutions for juvenile offenders, answered the CTI during an individual interview. Results show that the French translation of the CTI follows an identical factorial structure as the Epstein's American version in both adolescents and young adults, and that its internal consistency is satisfactory. Differences in Constructive Thinking profiles according to gender and age and between Swiss and American samples, are discussed. Juvenile offenders differed from community youths on most of the scales, speaking for a good discriminant validity of the CTI. In conclusion, the French translation of the CTI appears to preserve the original version's psychometric properties. The present study provides normative values from a community sample of Swiss adolescents and young adults.

Religious beliefs in schizophrenia: Their relevance for adherence to treatment

The study examined how religious beliefs and practices impact upon medication and illness representations in chronic schizophrenia. One hundred three stabilized patients were included in Geneva's outpatient public psychiatric facility in Switzerland. Interviews were conducted to investigate spiritual and religious beliefs and religious practices and religious coping. Medication adherence was assessed through questions to patients and to their psychiatrists and by a systematic blood drug monitoring. Thirty-two percent of patients were partially or totally nonadherent to oral medication. Fifty-eight percent of patients were Christians, 2% Jewish, 3% Muslim, 4% Buddhist, 14% belonged to various minority or syncretic religious movements, and 19% had no religious affiliation. Two thirds of the total sample considered spirituality as very important or even essential in everyday life. Fifty-seven percent of patients had a representation of their illness directly influenced by their spiritual beliefs (positively in 31% and negatively in 26%). Religious representations of illness were prominent in nonadherent patients. Thirty-one percent of nonadherent patients and 27% of partially adherent patients underlined an incompatibility or contradiction between their religion and taking medication, versus 8% of adherent patients. Religion and spirituality contribute to shaping representations of disease and attitudes toward medical treatment in patients with schizophrenia. This dimension should be on the agenda of psychiatrists working with patients with schizophrenia.

Liming influence on soil chemical properties, nutritional status and yield of alfalfa grown in acid soil

Alfalfa is an important forage crop with high nutritive value, although highly susceptible to soil acidity. Liming is one of the most efficient and prevailing practices to correct soil acidity and improve alfalfa yield. The objective of this study was to evaluate response to liming of alfalfa grown in a greenhouse on a Typic Quartzipsamment soil. The treatments consisted of four lime rates (0, 3.8, 6.6 and 10.3 Mg ha-1) and two cuts. Alfalfa dry matter increased quadratically with increasing lime rates. In general, dry matter yield was maximized by a lime rate of 8.0 Mg ha-1. Except for the control, the dry matter nutrient contents in the treatments were adequate. The positive linear correlation between root and nodule dry matter with lime rates indicated improvement of these plant traits with decreasing soil acidity. The soil acidity indices pH, base saturation, Ca2+ concentration, Mg2+ concentration, and H + Al were relevant factors in the assessment of alfalfa yield. The magnitude of influence of these soil acidity indices on yield as determined by the coefficient of determination (R²) varied and decreased in the order: base saturation, H + Al, pH, Ca and Mg concentrations. Optimum values of selected soil chemical properties were defined for maximum shoot dry matter; these values can serve as a guideline for alfalfa liming to improve the yield of this forage on acid soils.

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.

In vivo survival of teicoplanin-resistant Staphylococcus aureus and fitness cost of teicoplanin resistance.

Glycopeptide resistance, in a set of in vitro step-selected teicoplanin-resistant mutants derived from susceptible Staphylococcus aureus SA113, was associated with slower growth, thickening of the bacterial cell wall, increased N-acetylglucosamine incorporation, and decreased hemolysis. Differential transcriptome analysis showed that as resistance increased, some virulence-associated genes became downregulated. In a mouse tissue cage infection model, an inoculum of 10(4) CFU of strain SA113 rapidly produced a high-bacterial-load infection, which triggered MIP-2 release, leukocyte infiltration, and reduced leukocyte viability. In contrast, with the same inoculum of the isogenic glycopeptide-resistant derivative NM67, CFU initially decreased, resulting in the elimination of the mutant in three out of seven cages. In the four cages in which NM67 survived, it partially regained wild-type characteristics, including thinning of the cell wall, reduced N-acetylglucosamine uptake, and increased hemolysis; however, the survivors also became teicoplanin hypersusceptible. The elimination of the teicoplanin-resistant mutants and selection of teicoplanin-hypersusceptible survivors in the tissue cages indicated that glycopeptide resistance imposes a fitness burden on S. aureus and is selected against in vivo, with restoration of fitness incurring the price of resistance loss.

EULAR recommendations for the management of large-vessel vasculitis.

Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. Methods: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.

EULAR recommendations for the management of primary small and medium vessel vasculitis.

Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.

Soil tillage affects the community structure of mycorrhizal fungi in maize roots

In this study we tested whether communities of arbuscular mycorrhizal fungi (AMF) colonizing the roots of maize (Zea mays L.) were affected by soil tillage practices (plowing, chiseling, and no-till) in a long-term field experiment carried out in Tanikon (Switzerland). AMF were identified in the roots using specific polymerase chain reaction (PCR) markers that had been developed for the AMF previously isolated from the soils of the studied site. A nested PCR procedure with primers of increased specificity (eukaryotic, then, fungal, then AMF species or. species-grouop specific) was used. Sequencing of amplified DNA confirmed that the DNA obtained from the maize roots was of AMF origin. Presence of particular AMF species or species-group was scored as a presence of a DNA product after PCR with specific primers. We also used single-strand conformation polymorphism analysis (SSCP), of amplified DNA samples to-check if the amplification of the DNA from maize roots matched the expected profile for a particular AMF isolate with a given specific primer pair. Presence of the genus Scutellospora, in maize roots was strongly reduced in plowed and chiseled soils. Fungi from the suborder Glomineae were more prevalent colonizers of maize roots growing in plowed soils, but were also present in the roots from other tillage treatments. These changes in community of AMF colonizing maize roots might be due to (1), the differences in tolerance to the tillage-induced disruption of the hyphae among the different AMF species, (2) changes in nutrient content of the soil, (3) changes in microbial activity, or (4) changes in weed populations in response to soil tillage. This is the first report on community composition of AMF in the roots of a field-grown crop plant (maize) as affected by soil tillage.