Correction to: Efficacy of certolizumab pegol with and without concomitant use of disease-modifying anti-rheumatic drugs over 4 years in psoriatic arthritis patients: results from the RAPID-PsA randomized controlled trial.

The above article originally published with an error present in Discussion section and presented correctly in this article. The original article was corrected.

Efficacy of certolizumab pegol with and without concomitant use of disease-modifying anti-rheumatic drugs over 4 years in psoriatic arthritis patients: results from the RAPID-PsA randomized controlled trial.

To report long-term efficacy of certolizumab pegol (CZP) treatment with and without concomitant DMARDs in patients with psoriatic arthritis (PsA). RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to week 24, dose-blind to week 48, and open-label to week 216. Patients had active PsA with ≥ 1 failed DMARD. At baseline, patients were randomized 1:1:1 to CZP 200 mg every 2 weeks: CZP 400 mg every 4 weeks: placebo. CZP-randomized patients continued their dose into open-label. Observed case efficacy data are reported to week 216 for week 0 CZP-randomized patients (dose combined) with and without baseline DMARD use (DMARD+/DMARD-). Dactylitis (tenderness and ≥ 10% difference in swelling between affected and opposite digits) and enthesitis were measured using Leeds Dactylitis Index (LDI) and Leeds Enthesitis Index (LEI). 273/409 randomized patients received CZP from baseline: 199/273 (72.9%) DMARD+ and 74/273 (27.1%) DMARD- patients. 141/199 (70.9%) DMARD+ and 42/74 (56.8%) DMARD- patients completed Week 216. DMARD+ (79.7%) and 83.3% of DMARD- patients achieved ACR20 response at week 216; 79.2 and 78.1% achieved 75% improvement from baseline in Psoriasis Area and Severity Index (PASI75). High proportions of DMARD+/DMARD- patients with extra-articular manifestations at baseline reported total resolution at week 216; dactylitis 91.4% of DMARD+ and 93.3% of DMARD- patients, enthesitis 74.4% of DMARD+ and 87.5% of DMARD- patients. Long-term improvements in PsA symptoms were observed with CZP monotherapy or concomitant DMARDs, across important psoriatic disease domains, including joint disease, psoriasis, nail disease, dactylitis, and enthesitis.Trial registration: NCT01087788.

Vaginal microbicides save money: a model of cost-effectiveness in South Africa and the USA.

OBJECTIVE: To determine the hypothetical cost-effectiveness of vaginal microbicides preventing male to female HIV transmission. METHODS: A mathematical epidemiological and cost-effectiveness model using data from South Africa and the USA was used. The prospective 1-year-long intervention targeted a general population of women in a city of 1,000,000 inhabitants in two very different epidemiological settings, South Africa with a male HIV prevalence of 18.80% and the USA with a male HIV prevalence of 0.72%. The base case scenario assumes a microbicide effective at 55%, used in 30% of sexual episodes at a retail price for the public sector in South Africa of US$0.51 per use and in the USA of US$2.23 per use. RESULTS: In South Africa, over 1 year, the intervention would prevent 1908 infections, save US$6712 per infection averted as compared with antiretroviral treatment. In the USA, it would be more costly: over 1 year, the intervention would prevent 21 infections, amounting to a net cost per infection averted of US$405,077. However, in the setting of Washington DC, with a higher HIV prevalence, the same intervention would prevent 93 infections and save US$91,176 per infection averted. Sensitivity analyses were conducted and even a microbicide with a low effectiveness of 30% would still save healthcare costs in South Africa. CONCLUSIONS: A microbicide intervention is likely to be very cost-effective in a country undergoing a high-level generalised epidemic such as South Africa, but is unlikely to be cost-effective in a developed country presenting epidemiological features similar to the USA unless the male HIV prevalence exceeds 2.4%.

Identification of new isolates of Turnip mosaic virus that cluster with less common viral strains.

Turnip mosaic virus (TuMV) was found infecting cultivated brassicas and wild and cultivated ornamental Brassicaceae plants in different regions of Spain. Five new TuMV isolates, originating from different host plant species (Brassica cretica, Brassica juncea, Brassica napus, Eruca vesicaria subsp. sativa and Sisymbrium orientale), have been identified. The nucleotide sequences of the coat protein (CP) genes of the five isolates were determined. Phylogenetic analysis of the CP sequences showed that the five isolates grouped into two different clusters. The three isolates from the central region of Spain clustered with a previously reported Pisum sativum isolate from southeastern Spain, whereas the other two isolates from the eastern region clustered with two Italian and two Greek isolates. Both clusters were genetically distinct and belonged to the multi-lineage group OBR. The OBR group contains mainly TuMV isolates from hosts other than Brassica spp. and Raphanus sativus and mostly originating from Mediterranean countries. These new sequences provide further phylogenetic resolution of the OBR group. Although new TuMV isolates have been found in Spain, they were not associated with any serious disease outbreaks.

Genetic mapping of the novel Turnip mosaic virus resistance gene TuRB03 in Brassica napus.

A new source of resistance to the pathotype 4 isolate of Turnip mosaic virus (TuMV) CDN 1 has been identified in Brassica napus (oilseed rape). Analysis of segregation of resistance to TuMV isolate CDN 1 in a backcross generation following a cross between a resistant and a susceptible B. napus line showed that the resistance was dominant and monogenic. Molecular markers linked to this dominant resistance were identified using amplified fragment length polymorphism (AFLP) and microsatellite bulk segregant analysis. Bulks consisted of individuals from a BC(1) population with the resistant or the susceptible phenotype following challenge with CDN 1. One AFLP and six microsatellite markers were associated with the resistance locus, named TuRB03, and these mapped to the same region on chromosome N6 as a previously mapped TuMV resistance gene TuRB01. Further testing of TuRB03 with other TuMV isolates showed that it was not effective against all pathotype 4 isolates. It was effective against some, but not all pathotype 3 isolates tested. It provided further resolution of TuMV pathotypes by sub-dividing pathotypes 3 and 4. TuRB03 also provides a new source of resistance for combining with other resistances in our attempts to generate durable resistance to this virus.

The phylogeny of Turnip mosaic virus; comparisons of 38 genomic sequences reveal a Eurasian origin and a recent 'emergence' in east Asia.

The genomes of a representative world-wide collection of 32 Turnip mosaic virus (TuMV) isolates were sequenced and these, together with six previously reported sequences, were analysed. At least one-fifth of the sequences were recombinant. In phylogenetic analyses, using genomic sequences of Japanese yam mosaic virus as an outgroup, the TuMV sequences that did not show clear recombination formed a monophyletic group with four well-supported lineages. These groupings correlated with differences in pathogenicity and provenance; the sister group to all others was of Eurasian B-strain isolates from nonbrassicas, and probably represents the ancestral TuMV population, and the most recently 'emerged' branch of the population was probably that of the BR-strain isolates found only in east Asia. Eight isolates, all from east Asia, were clear recombinants, probably the progeny of recent recombination events, whereas a similar number, from other parts of the world, were seemingly older recombinants. This difference indicates that the presence of clear recombinants in a subpopulation may be a molecular signature of a recent 'emergence'.

Strains of Turnip mosaic potyvirus as defined by the molecular analysis of the coat protein gene of the virus.

Turnip mosaic virus (TuMV) is a member of the potyvirus genus with a wide host range and highly variable in its biological characteristics. Analysis of the CP gene sequences from databases, combined with the experimental analysis of the CP gene of further isolates, using data derived from sequence or restriction analysis, has allowed the genetic classification of 60 TuMV isolates or sequences. Two main genetic clusters MB (mostly Brassica isolates) and MR (mostly Radish isolates) were found, together with several apparently independent lineages. Isolates in the latter could be grouped as Intermediate between Brassica and Radish clusters (IBR) or outside Brassica and Radish clusters (OBR), according to their genetic distance to the main clusters. The genetic diversity of TuMV isolates deposited in the databases was increased with the sequences of the CP gene of seven selected isolates, mainly belonging to IBR or OBR groups. There was a correlation between the MR genetic cluster and JPN 1 serotype.

Involvement of Beet western yellows virus, Cauliflower mosaic virus, and Turnip mosaic virus in Internal Disorders of Stored White Cabbage.

ABSTRACT Experiments over two growing seasons clearly showed that Turnip mosaic virus (TuMV) infection was associated with internal necrosis (sunken necrotic spots 5 to 10 mm in diameter) and Beet western yellows virus (BWYV) infection was associated with collapse of leaf tissue at the margins (tipburn) in heads of stored white cabbage (Brassica oleracea var. capitata). Virtually no tipburn was seen in cv. Polinius, whereas cv. Impala was affected severely. Internal necrotic spots were seen in both cultivars. BWYV appeared to interact with TuMV. Plants infected with both viruses showed a lower incidence of external symptoms and had less internal necrosis than plants infected with TuMV alone. Cauliflower mosaic virus (CaMV) did not induce significant amounts of internal necrosis or tipburn, but did, in most cases, exacerbate symptoms caused by TuMV and BWYV. BWYV-induced tipburn worsened significantly during storage. Post-transplanting inoculation with TuMV induced more internal necrosis than pre-transplant inoculation. There was a significant association between detection of TuMV just prior to harvest and subsequent development of internal necrotic spots. Individually, all three viruses significantly reduced the yield of cv. Polinius, whereas only BWYV and CaMV treatments reduced the yield of cv. Impala.

Critical assessment of the outcome of infrainguinal vein bypass.

OBJECTIVE: To perform a more critical assessment of infrainguinal vein bypass. SUMMARY BACKGROUND DATA: Graft patency may give an unrealistic impression of the outcome of bypass surgery. METHODS: During a 6-year period, 236 patients undergoing primary vein grafts were entered into the study. An ideal outcome required the patient to have survived 12 months with a patent graft on duplex scanning, no perioperative complication, and no further related open or endovascular surgery or admission. RESULTS: At 12 months, the secondary graft patency rate was 82%; however, only 22% of patients had an ideal outcome. At 1 year, 44 (19%) patients died, 93 (39%) required further ipsilateral and 39 (17%) contralateral intervention, and a total of 108 (46%) were readmitted. An ideal outcome was more likely in patients receiving calcium channel blockers, principally because of improved primary patency, and less likely in those with cardiac failure requiring furosemide, principally because of worse survival in these patients. CONCLUSIONS: Few patients achieve an ideal result after infrainguinal vein bypass. Outcome may be improved by the use of calcium channel blockers. Careful consideration is required before performing revascularization in patients with cardiac failure.

A confirmatory factor analysis on the DSM-IV ADHD and ODD symptoms: what is the best model for the organization of these symptoms?

Confirmatory factor analysis (CFA) was used to evaluate five different models for the organization of the DSM-IV ADHD and oppositional defiant disorder (ODD) symptoms (Model 1: a single factor model; Model 2: an ADHD and ODD two factor model; Model 3a: an inattention (INA), hyperactivity/impulsivity (HYP/IMP), and ODD three factor model; Model 3b: an INA, HYP/IMP, and ODD three factor model where the three IMP symptoms cross-load on the ODD factor; Model 4: an INA, HYP, IMP, and ODD four factor model). To evaluate these models, maternal ratings of ADHD and ODD symptoms were obtained at outpatient pediatric clinics on 742 children not in treatment and 91 children in treatment for ADHD. Model 3a resulted in a good fit as well as a significantly better fit than Model 2. Model 3a was also equivalent across treatment status, gender, and age groupings for the most part. Though Models 3b and 4 provided a statistically better fit than Model 3a, the improvement in fit was small and other model selection criteria argued against these more complex models.

The cylindrical inclusion gene of Turnip mosaic virus encodes a pathogenic determinant to the Brassica resistance gene TuRB01.

The viral component of Turnip mosaic virus (TuMV) determining virulence to the Brassica napus TuRB01 dominant resistance allele has been identified. Sequence comparisons of an infectious cDNA clone of the UK 1 isolate of TuMV (avirulent on TuRB01) and a spontaneous mutant capable of infecting plants possessing TuRB01 suggested that a single nucleotide change in the cylindrical inclusion (CI) protein coding region (gene) of the virus was responsible for the altered phenotype. A second spontaneous mutation involved a different change in the CI gene. The construction of chimeric genomes and subsequent inoculations to plant lines segregating for TuRB01 confirmed the involvement of the CI gene in this interaction. Site-directed mutagenesis of the viral coat protein (CP) gene at the ninth nucleotide was carried out to investigate its interaction with TuRB01. The identity of this nucleotide in the CP gene did not affect the outcome of the viral infection. Both mutations identified in the CI gene caused amino acid changes in the C terminal third of the protein, outside any of the conserved sequences reported to be associated with helicase or cell-to-cell transport activities. This is the first example of a potyvirus CI gene acting as a determinant for a genotype-specific resistance interaction.

Detection of experimentally produced occult microfractures at the bone-cartilage interface in decalcified sections.

We compared three histological preparation methods to detect experimentally produced occult microfractures in decalcified human patellae: a paraffin tape-transfer technique, a paraffin slab-cut method, and a paraffin method with methyl salicylate as the clearing agent. Microfractures were observed at the bone-cartilage interface and were oriented either parallel or perpendicular to the tidemark. Both types of microfractures were documented with each preparation method. The slab-cut method was time-consuming, but the section thickness allowed detailed analysis of the architecture of microcracks as they passed into the depth of the section. The methyl salicylate method was efficient and produced thin, serial sections with good morphological detail and minimal cutting artifact. Reliable histological data were also derived from the tape-transfer technique, but this method was inconsistent. The methods summarized here for processing decalcified human joint tissues provide a basis for future orthopaedic studies investigating occult microfractures at the bone-cartilage interface.

Radial artery use in bypass grafting does not change digital blood flow or hand function.

BACKGROUND: Patient selection criteria have not been clearly established for use of the radial artery as a bypass conduit. To help establish such criteria, we measured changes in digital blood flow and hand function after radial artery removal. METHODS: Ninety-eight patients of the first 122 consecutive patients considered for radial artery harvest met predetermined criteria by vascular noninvasive studies to undergo removal of the radial artery. In 42 of these 98 patients, the radial artery was actually used as a bypass conduit; 28 of these 42 patients returned for noninvasive vascular studies, a critical review of hand function, and a hand symptom questionnaire. RESULTS: There were no significant differences between the operated and nonoperated hands for digital-brachial indices, cold response, grip or pinch strength, digital two-point discrimination, or nine-hole peg tests. The patients had an increased incidence of a small amount of forearm numbness and tingling, but no increase of pain or cold intolerance. CONCLUSIONS: For properly selected patients, there are minimal changes in hand function after radial artery removal.

Internal validity of attention deficit hyperactivity disorder, oppositional defiant disorder, and overt conduct disorder symptoms in young children: implications from teacher ratings for a dimensional approach to symptom validity.

Uses a dimensional approach to evaluate the internal validity of the attention deficit hyperactivity disorder (ADHD) inattention (I) and hyperactivity/impulsivity (H/I), oppositional defiant disorder (ODD), and overt conduct disorder (CD) symptoms (i.e., whether a symptom has a stronger correlation with its own dimension than the other three dimensions). In Study 1, teachers rated 1,445 children on the DSM-III-R I, H/I, ODD, and overt CD symptoms. In Study 2, teachers rated 1,711 children on the DSM-IV I, H/I, ODD, and overt CD symptoms. All the I symptoms showed internal validity in both studies. In contrast, the H/I symptoms and the ODD symptoms, especially the H/I symptoms, showed weaker internal validity. All the overt CD symptoms showed internal validity except the DSM-IV bullies others symptom, with this symptom being more strongly related to the ODD dimension. Confirmatory factor analysis provided support for a 4-factor model consisting of I, H/I, ODD, and overt CD factors. Finally, the importance of internal validity for the construct validation of the disruptive behavior symptoms is discussed.

Internal validity of the disruptive behavior disorder symptoms: implications from parent ratings for a dimensional approach to symptom validity.

A dimensional approach was used to evaluate the internal validity of the DSM-III-R ADHD-inattention, ADHD-hyperactivity/impulsivity, oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms (i.e., whether a symptom has a stronger correlation with its own dimension that the other three). Parents rated 4,019 children between the ages of 2 and 19 on these symptoms. The results showed that 5 of the 6 inattention symptoms, 3 of the 4 hyperactivity symptoms, 1 of the 4 impulsivity symptoms, 6 of the 9 oppositional defiant disorder symptoms, and 8 of the 11 CD symptoms had significant internal validity. Confirmatory factor analysis (CFA) found support for inattention, hyperactivity/impulsivity, oppositional defiant, and conduct disorder dimensions. Multiple-group CFA also found support for factor pattern and loading invariance across gender. The implications of these results as well as the merits of the dimensional approach to symptom validity are discussed in the context of the DSM-IV changes in ADHD, ODD, and CD.

Characterization of the growth center of the avian preovulatory follicle.

Anatomical studies have suggested that the germinal disc (GD) region (GDR; GD plus overlying granulosa cells) is the growth center of the avian preovulatory follicle. The objective of this study was to characterize the physiology of the GDR by comparing the functions of two morphologically distinct populations of granulosa cells. The three markers of the physiology of individual granulosa cells examined were 1) proliferation, 2) production of plasminogen activator (PA), and 3) production of progesterone. The effect of LH on each of these functions was also evaluated. Sections 8 mm in diameter were obtained from granulosa cells associated with the GD (GD granulosa cells) and from granulosa cells on the layer distal to the GD (nonGD granulosa cells) from the five largest preovulatory follicles (F5-F1, F1 designated the largest) 12-14 h (before the LH surge) or 2 h (after the LH surge) before ovulation. Proliferation was measured using [3H]thymidine incorporation. PA activity was measured using the chromogenic substrate S-2251. Progesterone was measured by RIA. Incorporation of [3H]thymidine was very high in GD and nonGD granulosa cells from F5 and F4 follicles and decreased dramatically as the follicle progressed through the hierarchy, but remained significantly higher in GD granulosa cells compared to nonGD granulosa cells at all stages of development examined (F5-F1). Exposure of follicles to LH in vivo inhibited [3H]thymidine incorporation by GD granulosa cells in all follicles except the F5. In contrast, in vivo exposure to LH had no effect on [3H]thymidine incorporation by nonGD granulosa cells. PA production by GD granulosa cells was high throughout the stages of maturation studied (F5-F1), whereas PA production by nonGD granulosa cells decreased as follicles matured from F5 to F1. Interestingly, LH stimulated PA production by F5 GD granulosa cells, had no effect on PA production by F3 GD granulosa cells, and inhibited PA production by F1 GD granulosa cells. In contrast, LH inhibited PA production by nonGD granulosa cells in F3 and F1 follicles. Progesterone production by GD granulosa cells was low in F3 and F1 follicles. Progesterone production by nonGD granulosa cells increased as the follicle matured from the F3 to F1 stage and was stimulated significantly by LH. These data indicate that physiological differences in granulosa cell function are dependent upon the location of granulosa cells relative to the GD. GD granulosa cells are less mature, proliferate more rapidly, and produce more PA than nonGD granulosa cells, which produce more progesterone and less PA. Differences in granulosa cell function may be due to the influence of the GD, providing physiological evidence that the GDR may be the growth center of the follicle.

Setting priorities for the Children's Vaccine Initiative: a cost-effectiveness approach.

To help the Children's Vaccine Initiative (CVI) achieve its goal of new and improved children's vaccines, we developed and applied a cost-effectiveness model to set priorities for vaccine development. The model measures the health benefits in additional Quality-Adjusted Life Years (QALYs) gained by the combined birth cohorts of all developing countries over an assumed useful life of a proposed vaccine (generally 10 years). It measures costs as the net cost of developing, procuring, and administering the vaccine to the same population and time frame compared to the status quo (the current vaccine, if any). It weights each dollar of in-kind allocation of the existing health infrastructure less heavily than a dollar cash outlay to purchase new vaccine to reflect severe constraints on foreign exchange and non-personnel costs. It expresses cost-effectiveness as the net cost per QALY. The model was applied to 13 candidate vaccines selected by the CVI for initial analysis on the basis of their near-term feasibility. The five most cost-effective improvements, each of which could generate a QALY inexpensively (below $25 per QALY), were an early-administration or an early two-dose measles vaccine, slow release tetanus toxoid (for women), improved typhoid vaccine, and hepatitis B combined with diphtheria-tetanus-pertussis vaccine.

Colour duplex ultrasound: a screening modality for femoropopliteal disease in patients with intermittent claudication.

In patients presenting with intermittent claudication, Colour Duplex Ultrasound (CDU) examination of the femoro-popliteal segment has been proposed as a screening modality. Those patients with atheromatous lesions suitable for percutaneous transluminal angioplasty (PTA) could proceed to diagnostic angiography. Patients with long segment occlusive disease demonstrated by CDU, who were not considered suitable candidates for surgery, would not require angiographic examination. This prospective study was performed on 46 limbs in 25 consecutive patients who presented for investigation of claudication. There was close correlation between the two methods in the demonstration of high-grade stenoses and occluded segments. Using angiography as the 'gold standard' this study indicated a diagnostic accuracy for CDU of 93% with a sensitivity of 89% and a specificity of 95%. Angiography tended to show longer occluded segments than CDU. Colour Duplex Ultrasound shows promise as a screening investigation in patients with intermittent claudication to detect lesions that may be suitable for PTA.