The wave regimes of the Central Pacific Ocean with a focus on pearl farming atolls.

Pearl farming sustainability in South Central Pacific (SCP) atolls strongly depends on water quality and renewal. These factors are partly controlled by the wave conditions that impact the lagoon circulation. To characterize the wave conditions around 83 SCP atolls including those hosting pearl farming activities, we used 18 years of WaveWatchIII simulation with a grid refined from 50 to 5 km resolution. Three regional wave regimes are statistically identified: two associated with long distant swells originating from mid-latitude storms, and one with local trade winds. All regimes occur with a relatively high frequency (22-44%), but with a marked seasonality. Wave conditions are also strongly modified locally during their propagation between the archipelagoes. Western and southern isolated atolls generally have a single regime all around their rims. In contrast, central Tuamotu atolls experience different regimes depending on their levels of protection. These results help understanding atoll hydrodynamics, which has implications for their management.

Characterization of south central Pacific Ocean wind regimes in present and future climate for pearl farming application.

In the South Pacific (SP) pearl farming atolls, wind is the main driver of lagoon water circulation, affecting dispersal and survival of pearl oyster larvae. To characterize typical wind conditions in the SP, wind regime classifications are performed from regional climate simulations using the WRF model, for present-day and for the end of the 21st century under RCP8.5 scenario conditions. At the daily time-scale, 4 regimes are identified: a trade-wind, a north-easterly, and two easterly regimes. Their characteristics are driven by large-scale circulation and climate modes of variability. In future projection, all regimes are characterized by a ~15% wind speed increase, while directions and occurrence frequencies undergo marginal changes. At the monthly time-scale that corresponds to pearl oyster pelagic larval duration, nine wind regimes are determined including three regimes with wind reversals. These regimes can be used to model typical lagoon conditions during larval dispersal.

Impact of projected sea surface temperature biases on tropical cyclones projections in the South Pacific.

Climate model projections generally indicate fewer but more intense tropical cyclones (TCs) in response to increasing anthropogenic emissions. However these simulations suffer from long-standing biases in their Sea Surface Temperature (SST). While most studies investigating future changes in TC activity using high-resolution atmospheric models correct for the present-day SST bias, they do not consider the reliability of the projected SST changes from global climate models. The present study illustrates that future South Pacific TC activity changes are strongly sensitive to correcting the projected SST changes using an emergent constraint method. This additional correction indeed leads to a strong reduction of the cyclogenesis (-55%) over the South Pacific basin, while no statistically significant change arises in the uncorrected simulations. Cyclogenesis indices suggest that this strong reduction in the corrected experiment is caused by stronger vertical wind shear in response to a South Pacific Convergence Zone equatorward shift. We thus find that uncertainty in the projected SST patterns could strongly hamper the reliability of South Pacific TC projections. The strong sensitivity found in the current study will need to be investigated with other models, observational constraint methods and in other TC basins in order to assess the reliability of regional TC projections.

Analytical models approximating individual processes: a validation method.

Upscaling population models from fine to coarse resolutions, in space, time and/or level of description, allows the derivation of fast and tractable models based on a thorough knowledge of individual processes. The validity of such approximations is generally tested only on a limited range of parameter sets. A more general validation test, over a range of parameters, is proposed; this would estimate the error induced by the approximation, using the original model's stochastic variability as a reference. This method is illustrated by three examples taken from the field of epidemics transmitted by vectors that bite in a temporally cyclical pattern, that illustrate the use of the method: to estimate if an approximation over- or under-fits the original model; to invalidate an approximation; to rank possible approximations for their qualities. As a result, the application of the validation method to this field emphasizes the need to account for the vectors' biology in epidemic prediction models and to validate these against finer scale models.

[Fibromyalgia]. / La fibromyalgie.

PURPOSE: We review the current knowledge about fibromyalgia, adding to the clinical aspects, the nosology, epidemiology and pathogenesis. The therapeutic and social management of these suffering patients are discussed. KEY POINTS: The limitations of the American College of Rheumatology classification criteria used as diagnostic criteria are discussed. Fibromyalgia is not a simple psychiatric disorder, even if psychiatric symptoms are constantly found. Based on functional brain imaging, there is some evidence pointing to an abnormal function of the supra-spinal centres for pain regulation. CONCLUSION: Fibromyalgia is a clinical autonomous entity. Physiopathology knowledge is improving, but must be confirmed by new research. Patients will take profit of multimodal individualized treatment programs, including explanations about the diagnosis. In most cases, fibromyalgia is compatible with the maintenance of a professional activity, possibly adapted to the patient. Recognized disability requiring compensation is infrequent.

Early determination of the reproductive number for vector-borne diseases: the case of dengue in Brazil.

OBJECTIVE: To evaluate a new method of deriving the reproductive number for vector-borne diseases from the early epidemic curves for vector-borne diseases with incubations in the vectors and in the hosts. METHOD: We applied the model to several dengue epidemics in different climatic regions of Brazil: Brasilia, Belém, Fortaleza, Boa Vista. RESULTS: The new method leads to higher estimates of the reproductive number than previous models. CONCLUSION: At present, Aedes aegypti densities, the meeting of more compatible strains of viruses and mosquitoes, may lead to re-emergence of urban yellow fever epidemics.

Total joint replacement of hip or knee as an outcome measure for structure modifying trials in osteoarthritis.

OBJECTIVE: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working group to assess the value of time to joint surgery as a potential therapeutic failure outcome criterion for osteoarthritis (OA) of the hip or knee in the assessment of potential structure modifying agents. METHODS: PubMed was searched for manuscripts from 1976 to 2004. Relevant studies were discussed at a 1-day meeting. RESULTS: There are no accepted guidelines for 'time to' and 'indications for' joint replacement surgery. A limited number of trials have examined joint replacement surgery within the study population. Several parameters, particularly joint space narrowing (interbone distance), correlate with surgical intervention. However, at the level of the knee, none of the parameters have positive predictive value for joint replacement surgery better than 30%. In contrast, lack of significant joint space narrowing has a strong negative predictive value for joint replacement surgery (>90%), that remains after controlling for OA pain severity. CONCLUSION: At this time, GREES cannot recommend time to joint surgery as a primary endpoint of failure for structure modifying trials of hip or knee OA-as the parameter has sensitivity but lacks specificity. In contrast, in existing trials, a lack of progression of joint space narrowing has predictive value of >90% for not having surgery. GREES suggests utilizing joint space narrowing (e.g., >0.3-0.7 mm) combined with a lack of clinically relevant improvement in symptoms (e.g., >/=20-25%) for 'failure' of a secondary outcome in structure modifying trials of the hip and knee.

Better results with rhenium-186 radiosynoviorthesis than with cortivazol in rheumatoid arthritis (RA): a two-year follow-up randomized controlled multicentre study.

OBJECTIVE: The aim of this international multicentric randomized phase 3 clinical trial was to compare prospectively radiosynoviorthesis (RSO) with rhenium-186-sulfide (186Re) to intra-articular corticotherapy in patients with clinically controlled rheumatoid arthritis (RA), but in whom one or a few medium-sized joints remained painful or swollen. METHODS: One hundred and twenty-nine joints in 81 RA patients [stratified into 2 groups: wrists (group 1, n = 78) and all the other joints (group 2, n = 51, including 18 elbows, 21 shoulders and 12 ankles)] were randomized to receive intra-articular injections of either 186Re-sulfide (64 +/- 4 MBq), or cortivazol (Altim) 3.75 mg. Clinical assessment was performed before and then at 3, 6, 12, 18 and 24 months after local therapy, using a 4-step verbal rating scale (VRS) and a 100 mm visual analog scale for pain, a 4-step VRS for joint swelling and mobility and a 2-step VRS for the radiological stage. The Mantel-Haenszel test was used for qualitative variables, analysis of variance (ANOVA) for quantitative pain analysis and Kaplan-Meyer survival test for relapse analysis. RESULTS: 186Re was observed to be statistically superior to cortivazol at 18 and 24 months while no statistical difference was seen for any criterion at 3, 6 and 12 months post injection. At 24 months, the difference in favor of 186Re was significant for pain (p = 0.024), joint swelling (p = 0.01), mobility (p = 0.05, non-wrists only), pain and swelling (p = 0.03) and pain or swelling (p = 0.02). "Survival" studies (Kaplan-Meyer) demonstrated a greater relative risk of relapse in corticoid treated joints, but only from the second year of follow-up. No serious side effect was observed in any patient, with only light and transient local pain and/or swelling occurring in 24% of cases, regardless of the treatment used. CONCLUSION: 186Re-sulfide and cortivazol had similar efficacy up to 12 months post-injection, but 186Re became clearly more effective at 18 and 24 months, for all criteria monitored and for RA outcome. Therefore, 186Re RSO can be recommended for routine clinical use.

Sacral inflammatory pseudotumor revealed by paraneoplastic syndrome.

There is still debate on whether inflammatory pseudotumor should be considered benign or malignant. This lesion has only been reported twice in bone, apart from cases complicating foreign body reaction to joint replacement arthroplasty. We report here a third case, localized at the sacrum. A 31-year-old man had inflammatory dorsalgia and polyarthralgia without synovitis but with fever, asthenia, and erythema nodosa. Biological tests and X-rays were not informative, but technetium scintigraphy revealed a high level of left sacroiliac tracer binding. Several nonsteroidal anti-inflammatory drugs and sulfasalazine treatment were given over 3 months but ineffective. Pelvic magnetic resonance imaging showed an osteolytic tumor of the sacrum. Biopsy suggested a malignant fibrosarcoma, but complete evaluation after surgical resection demonstrated an inflammatory pseudotumor. All clinical symptoms disappeared within a few days after surgery, which is suggestive of a paraneoplastic syndrome. No relapse has occurred after 4 years.

169Erbium-citrate synoviorthesis after failure of local corticosteroid injections to treat rheumatoid arthritis-affected finger joints.

OBJECTIVES: Intra-articular injection of 169Erbium-citrate (169Er-citrate; radiosynoviorthesis or radiosynovectomy) is an effective local treatment of rheumatic joint diseases. However, its efficacy in corticosteroid-resistant rheumatoid arthritis-affected joints has not been clearly demonstrated. METHODS: A double-blind, randomised, placebo-controlled, international multicentre study was conducted in patients with rheumatoid arthritis with recent (< or = 24 months) ineffective corticosteroid injection(s) into their finger joint(s). Eighty-five finger joints of 44 patients were randomised to receive a single injection of placebo (NaCl 0.9%) or 169Er-citrate. Results of evaluation 6 months later were available for 82 joints (46 metacarpophalangeal and 36 proximal interphalangeal joints) of 42 patients: 39 169Er-citrate-injected joints and 43 placebo-injected joints. Efficacy was assessed using a rating scale for joint pain, swelling and mobility. RESULTS: Intent-to-treat analysis of the results of the 82 joints showed a significant effect of 169Er-citrate compared to placebo for the principal criteria decreased pain or swelling (95 vs 79%; p = 0.038) and decreased pain and swelling (79 vs 47%; p = 0.0024) and for the secondary criteria decreased pain (92 vs 72%; p = 0.017), decreased swelling (82 vs 53%; p = 0.0065) and increased mobility (64 vs 42%; p = 0.036). Per-protocol analysis, excluding 18 joints of patients who markedly changed their usual systemic treatment for arthritis, gave similar percentages of improvement but statistical significance was lower owing the reduced power of the statistical tests. CONCLUSION: These results confirm the clinical efficacy of 169Er-citrate synoviorthesis of rheumatoid arthritis-diseased finger joints after recent failure of intra-articular corticotherapy.

Quantitative assessment of joint space width with an electronic caliper.

UNLABELLED: The progression of joint space narrowing (JSN) is considered to be the best available marker of osteoarthritis (OA) progression. Several techniques have been proposed for the measurement of joint space at its narrowest point in OA of the hips and knees. OBJECTIVE: To evaluate the properties of the technique using an electronic caliper for the measurement of JSN in OA patients. DESIGN: We used an electronic caliper to measure joint space width (JSW) for hips on 100 plain radiographs. JSW was measured in the vertical position at the center of the femoral head. Femoral head diameter was also determined to correct for variations due to differences in magnification of digitized X-rays. All films were read twice by each of two rheumatologists (one junior, one senior) and two radiologists (one junior, one senior). Intraclass correlation coefficients and their 95% confidence intervals were calculated. RESULTS: Detailed results are given for right hips (38 with OA, 18 inflammatory, 44 normal); very similar results were obtained for left hips. For JSW, the intraclass correlation coefficient was between 0.96 and 0.99 for intraobserver reliability. The level of reliability was similar for analysis of the diameter of the femoral head (R:0.84 to 0.98) and for the ratio of these two measurements (0.96 to 0.99). The most reliable measurements were those made by the senior radiologist, followed by those made by the two rheumatologists. In assessments of interobserver reliability for the measurement of JSW, R varied from 0.91 to 0.96 for the first reading and from 0.88 to 0.96 for the second reading. For the measurement of femoral head diameter, R varied from 0.86 to 0.96 for the first reading and from 0.74 to 0.96 for the second reading. CONCLUSION: The electronic caliper technique is an accurate method for measuring JSW in the hip. This technique seems to be reproducible, is simple, and could be used for routine evaluation. Further validation is required, with the measurement of serial X-rays from the same patients.

[Inducible nitric oxide synthase expression and nitric oxide production by monocytes in systemic sclerosis]. / Expression de la NO synthase inductible et production du monoxyde d'azote par les cellules mononucléées sanguines dans la sclérodermie systémique.

We investigated nitric oxide (NO) production and inducible NO synthase (iNOS) expression by cultured peripheral blood mononuclear cells (PBMC) in systemic sclerosis (SSc). Eighteen patients with SSc were compared to two control groups: 16 rheumatoid arthritis patients (RA) and 23 mechanical sciatica patients. The sum of nitrites and nitrates was determined by fluorimetry in sera and spectrophotometry in supernatants. Inducible iNOS was detected in cultured PBMC by immunofluorescence, immunoblot and flow cytometry with or without IL-1 beta + TNF alpha, IL-4 or IFN gamma from day 1 to day 5. NO metabolite concentrations in the plasma were lower in SSc (34.3 mumol/l +/- 2.63 SEM) than in RA (48.3 mumol/l +/- 2.2; p < 0.02) and sciatica (43.3 mumol/l +/- 5.24; p < 0.03) patients. iNOS was detected in cultured monocytes in the 3 groups but induction occurred on day 1 in RA, day 2 in sciatica and only on day 3 in SSc, whatever the stimulus. The concentrations of NO metabolites are decreased in SSc patients and the induction of iNOS in PBMC is delayed. Low levels of NO, a vasodilator, may be involved in vasospasm, which is critical in SSc. This may suggest therapeutic implications.

HLA class I and class II are both associated with the genetic predisposition to primary Sjögren syndrome.

Primary Sjögren syndrome (pSS) is an autoimmune disease characterized by progressive destruction of the exocrine glands leading to mucosal and conjunctival dryness. It is marked by lymphocytic infiltration of the glands and the accumulation of several types of autoantibodies such as rheumatoid factor (RF), antinuclear, anti-SS-A (anti-Ro) and anti-SS-B (anti-LA) autoantibodies. The susceptibility to pSS and/or the presence of SS-A/SS-B autoantibodies in pSS patients is associated with DRB1*03-DQB1*02 and DRB1*02-DQB1*06 haplotypes, whereas no associations have been described with any HLA class I allele. To define the impact of HLA class I alleles in predisposition to pSS, 46 patients responding to the European criteria and 222 healthy unrelated Caucasians were analyzed for their HLA class I and class II haplotypes. Our results confirm the association of the DRB1*03-DQB1*02 haplotype with SS-A/SS-B autoantibodies positive pSS and demonstrate a significant association of the HLA-A24 with the disease. Moreover, HLA-A24 is more often associated with DRB1*11-DQB1*0301 and/or DRB1*0301-DQB1*02 in pSS patients than in the controls. The novel association of HLA class I alleles with susceptibility to pSS provides new insights to the genetic predisposition to this disease and subsequently to its physiopathology.

Physical and biological dosimetry in patients undergoing radiosynoviorthesis with erbium-169 and rhenium-186.

Physical and biological dosimetry were investigated in 45 rheumatoid arthritis patients treated by radiosynoviorthesis (RSO) with 186Re-sulphide (medium-sized joints) and 169Er-citrate (digital joints). Biological dosimetry involved scoring dicentrics in lymphocytes, cultured from blood samples withdrawn just before and 6 h, 24 h and 7 days after treatment. Physical methods included repeated blood sample counts and scintigraphy data. For erbium-169 (pure beta emitter), only bremsstrahlung could be measured and solely in the injection area. For rhenium-186 (both beta and gamma emitter), whole body scans and static images of joints and locoregional lymph nodes were performed. Dosimetry calculations were in accordance with the MIRDOSE 3 software and tables. For erbium-169 (21 patients), either metacarpophalangeal (30 MBq) or proximal interphalangeal (20 MBq) joints of the hands were treated (one joint per patient); 18 patients (out of 21) were interpretable for biological dosimetry, 10 (out of 11) for physical dosimetry and six (out of 10) for both. For rhenium-186, 23 wrists, nine elbows, three shoulders and two ankles were injected in 24 patients, with a maximum of three joints per patient (70 MBq per joint); 20 patients (out of 24) and 10 (out of 10) were interpretable for biological and physical dosimetry, respectively, and eight (out of 10) for both methods. Erbium-169 biological dosimetry was negative in all interpretable patients, and physical dosimetry gave a blood dose of 15 +/- 29 microGy and an effective dose lower than 1 mSv/30 MBq. For rhenium-186, biological results were negative in 16 patients (out of 20), but showed a blood irradiation around 200 mGy in the last four. A significant cumulative increase of dicentrics 7 days after injection (16/10,000 instead of 5/10,000 prior to treatment; p < 0.04) was also noted. Gamma counts gave a blood dose of 23.9 +/- 19.8 mGy/70 MBq and the effective dose was found to be 26.7 +/- 5.1 mGy/70 MBq, i.e. about 380 microGy.MBq-1. Erbium-169 RSO is very safe from both physical and biological dosimetry standpoints. Rhenium-186 leak is greater, as demonstrated by the higher blood activity and the measurable, although limited, dicentrics induction in blood lymphocytes. However, the effective dose remains moderate, i.e. 30 times lower than in 131I therapy in benign thyroid diseases.

Management of a patient with sarcoid calcaneitis and dactylitis.

Dactylitis and calcaneitis developed in a patient with untreated sarcoidosis of the skin and lungs. Radiographs showed a defect in the second phalanx of the left middle finger. Radiographs of the feet were normal, but magnetic resonance imaging demonstrated a defect in the left calcaneus. Methylprednisolone therapy (1 g per day for 3 consecutive days) induced a dramatic improvement within 48 hours. Low-dose oral glucocorticoid therapy was given subsequently. One year later, a recurrent episode of dactylitis responded promptly to the same regimen. Maintenance therapy was given, and no further recurrences were noted during the four-year follow-up. Sarcoid bone lesions are uncommon and arise selectively in the small bones of the hands and feet. Involvement of the calcaneus is exceedingly rare, and its treatment is not standardized. In our patient, glucocorticoid therapy combined with methotrexate and hydroxychloroquine were effective in controlling the disease.

Inhibition of the nitrosothiol production of cultured osteoarthritic chondrocytes by rhein, cortisol and diclofenac.

OBJECTIVE: Nitric oxide (NO degrees ) is a free molecule produced by NO synthases which acts as a mediator in inflammatory processes. NO degrees can react with thiol groups of proteins to produce nitrosothiols. Increased concentrations of these bioactive compounds have been found in sera and synovial fluids from patients with osteoarthritis (OA). The aim of this study was to assess the ability of human osteoarthritic chondrocytes to synthesize nitrosothiols and to compare the in vitro effects of rhein, cortisol and diclofenac on nitrosothiol and nitrite production. METHODS: Osteoarthritic chondrocytes were incubated for 24 h with 1 ng/ml of recombinant human interleukin-1beta (IL-1beta) in the presence or absence of rhein (1.3x10(-5) M, 6.5x10(-6) M, or 1.3x10(-6) M), cortisol (10(-5) M) or diclofenac (10(-5) M or 10(-6) M). Nitrite levels were measured in cell supernatants by the Griess method; nitrosothiol levels were determined in supernatants and cellular lysates by fluorimetry. RESULTS: At the basal level, nitrosothiols represented 80% of the total of nitrite and nitrosothiol production. After IL-1beta stimulation, NO degrees production was highly increased in the supernatants (45-fold increase in nitrite, 60-fold increase in nitrosothiols) as well as in cell lysates (35-fold increase in nitrosothiols). Rhein caused a dose-dependent decrease in nitrosothiol and nitrite production. In comparison, diclofenac (10(-5) M) moderately decreased nitrite and nitrosothiol levels in the supernatants but had no effect on lysate nitrosothiol. Cortisol had no significant effect on NO degrees production. CONCLUSIONS: The IL-1beta stimulation increased nitrosothiol production by osteoarthritic chondrocytes. These results demonstrate the need to measure nitrosothiol as well as nitrite production. Rhein inhibited the IL-1beta induced NO degrees production, and may be a suitable treatment for osteoarthritis.

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.