Prevention of vitamin K deficiency bleeding with three oral mixed micellar phylloquinone doses: results of a 6-year (2005-2011) surveillance in Switzerland.

In 2003, the Swiss guidelines to prevent vitamin K deficiency bleeding (VKDB) were adapted. As two oral doses (2 mg, hour/day 4) of mixed micellar VK preparation had failed to abolish late VKDB, a third dose (week 4) was introduced. This report summarizes the new guidelines acceptance by Swiss pediatricians and the results of a prospective 6-year surveillance to study their influence on the incidence of VKDB. The new guidelines acceptance by Swiss pediatricians was evaluated by a questionnaire sent to all pediatricians of the Swiss Society of Paediatrics. With the help of the Swiss Paediatric Surveillance Unit, the incidence of VKDB was monitored prospectively from July 1, 2005 until June 30, 2011. Over a 6-year period (458,184 live births), there was one case of early and four cases of late VKDB. Overall incidence was 1.09/10(5) (95 % confidence intervals (CI) 0.4-2.6). Late VKDB incidence was 0.87/10(5) (95 % CI 0.24-2.24). All four infants with late VKDB had an undiagnosed cholestasis at the time of bleeding; parents of 3/4 had refused VK prophylaxis, and in 1/4, the third VK dose had been forgotten. Compared with historical control who had received only two oral doses of mixed micellar VK (18 cases for 475,372 live births), the incidence of late VKDB was significantly lower with three oral doses (Chi(2),Yates correction, P = 0.007). CONCLUSION: VKDB prophylaxis with 3 × 2 mg oral doses of mixed micellar VK seems to prevent adequately infants from VKDB. The main risk factors for VKDB in breast-fed infants are parental VK prophylaxis refusal or an unknown cholestasis.

Failure of the surgical treatment in 115 infected hip arthroplasties-­analysis of a 12-­year prosthetic joint cohort study (1999-­2010)

Background:¦Infection after total or partial hip arthroplasty (HA) leads to significant long-­term morbidity and high healthcare cost. We evaluated reasons for treatment failure of different surgical modalities in a 12-­year prosthetic hip joint infection cohort study.¦Method:¦All patients hospitalized at our institution with infected HA were included either retrospectively (1999-­‐2007) or prospectively¦(2008-­‐2010). HA infection was defined as growth of the same microorganism in ≥2 tissues or synovialfluid culture, visible purulence, sinus tract or acute inflammation on tissue histopathology. Outcome analysis was performed at outpatient visits, followed by contacting patients, their relatives and/or treating physicians afterwards.¦Results:¦During the study period, 117 patients with infected HA were identified. We excluded 2 patients due to missing data. The average age was 69 years (range, 33-­‐102 years); 42% were female. HA was mainly performed for osteoarthritis (n=84), followed by trauma (n=22), necrosis (n=4), dysplasia(n=2), rheumatoid arthritis (n=1), osteosarcoma (n=1) and tuberculosis (n=1). 28 infections occurred early(≤3 months), 25 delayed (3-­‐24 months) and 63 late (≥24 months after surgery). Infected HA were¦treated with (i) two-­‐stage exchange in 59 patients (51%, cure rate: 93%), (ii) one-­‐stage exchange in 5 (4.3%, cure rate: 100%), (iii) debridement with change of mobile parts in 18 (17%, cure rate: 83%), (iv) debridement without change of mobile¦parts in 17 (14%, cure rate : 53% ), (v) Girdlestone in 13 (11%, cure rate: 100%), and (vi) two-­‐stage exchange followed by¦removal in 3 (2.6%). Patients were followed for an average of 3.9 years (range, 0.1 to 9 years), 7 patients died unrelated to the infected HA. 15 patients (13%) needed additional operations, 1 for mechanical reasons(dislocation of spacer) and 14 for persistent infection: 11 treated with debridement and retention (8 without change; and 3 with change of mobile parts) and 3 with two-­‐stage exchange. The average number of surgery was 2.2 (range, 1 to 5). The infection was finally eradicated in all patients, but the functional outcome remained unsatisfactory in 20% (persistent pain or impaired mobility due to spacer or Girdlestone situation).¦Conclusions:¦Non-­‐respect of current treatment concept leads to treatment failure with subsequent operations. Precise analysis of each treatment failure can be used for improving the treatment algorithm leading to better results.

Level of accumulation of epoxy fatty acid in Arabidopsis thaliana expressing a linoleic acid delta12-epoxygenase is influenced by the availability of the substrate linoleic acid.

Arabidopsis thaliana (L.) Heynh. expressing the Crepis palaestina (L.) linoleic acid delta12-epoxygenase in its developing seeds typically accumulates low levels of vernolic acid (12,13-epoxy-octadec-cis-9-enoic acid) in comparison to levels found in seeds of the native C. palaestina. In order to determine some of the factors limiting the accumulation of this unusual fatty acid, we have examined the effects of increasing the availability of linoleic acid (9cis, 12cis-octadecadienoic acid), the substrate of the delta12-epoxygenase, on the quantity of epoxy fatty acids accumulating in transgenic A. thaliana. The addition of linoleic acid to liquid cultures of transgenic plants expressing the delta12-epoxygenase under the control of the cauliflower mosaic virus 35S promoter increased the amount of vernolic acid in vegetative tissues by 2.8-fold. In contrast, the addition to these cultures of linoelaidic acid (9trans, 12trans-octadecadienoic acid), which is not a substrate of the delta12-epoxygenase, resulted in a slight decrease in vernolic acid accumulation. Expression of the delta12-epoxygenase under the control of the napin promoter in the A. thaliana triple mutant fad3/fad7-1/fad9, which is deficient in the synthesis of tri-unsaturated fatty acids and has a 60% higher level of linoleic acid than the wild type, was found to increase the average vernolic acid content of the seeds by 55% compared to the expression of the delta12-epoxygenase in a wild-type background. Together, these results reveal that the availability of linoleic acid is an important factor affecting the synthesis of epoxy fatty acid in transgenic plants.

Iowa Department of Transportation Fiscal Year 2010 Report of Savings by Using Video Conferencing Through Iowa Communications Network to the Iowa General Assembly Pursuant to Iowa Code § II 84 Acts and Joint Resolutions Enacted at the 1994 Regular Session of the 75th General Assembly of the State of Iowa

Introduction and summary Iowa Code § 8D.10 requires certain state agencies to prepare an annual report to the General Assembly certifying the identified savings associated with that state agency’s use of the Iowa Communications Network (ICN). This report covers estimated cost savings related to video conferencing via ICN for the Iowa Department of Transportation (DOT). In FY 2010, the DOT did not conduct any sessions utilizing ICN’s video conferencing system. Therefore, no cost savings were calculated for this report.

Physicians' estimates of the 10-year cardiovascular risk in hypertensive patients

RESUME L'objectif de cette étude est d'évaluer comment de jeunes médecins en formation perçoivent le risque cardiovasculaire de leurs patients hypertendus en se basant sur les recommandations médicales (« guidelines ») et sur leur jugement clinique. Il s'agit d'une étude transversale observationnelle effectuée à la Policlinique Médicale Universitaire de Lausanne (PMU). 200 patients hypertendus ont été inclus dans l'étude ainsi qu'un groupe contrôle de 50 patients non hypertendus présentant au moins un facteur de risque cardiovasculaire. Nous avons comparé le risque cardiovasculaire à 10 ans calculé par un programme informatique basé sur l'équation de Framingham. L'équation a été adaptée pour les médecins par l'OMS-ISH au risque perçu, estimé cliniquement par les médecins. Les résultats de notre étude ont montrés que les médecins sous-estiment le risque cardiovasculaire à 10 ans de leurs patients, comparé au risque calculé selon l'équation de Framingham. La concordance entre les deux méthodes était de 39% pour les patients hypertendus et de 30% pour le groupe contrôle de patients non hypertendus. La sous-estimation du risque. cardiovasculaire pour les patients hypertendus était corrélée au fait qu'ils avaient une tension artérielle systolique stabilisée inférieure a 140 mmHg (OR=2.1 [1.1 ;4.1]). En conclusion, les résultats de cette étude montrent que les jeunes médecins en formation ont souvent une perception incorrecte du risque cardiovasculaire de leurs patients, avec une tendance à sous-estimer ce risque. Toutefois le risque calculé pourrait aussi être légèrement surestimé lorsqu'on applique l'équation de Framingham à la population suisse. Pour mettre en pratique une évaluation systématique des facteurs de risque en médecine de premier recours, un accent plus grand devrait être mis sur l'enseignement de l'évaluation du risque cardiovasculaire ainsi que sur la mise en oeuvre de programme pour l'amélioration de la qualité.

Relationships between grain yield and accumulation of biomass, nitrogen and phosphorus in common bean cultivars

Shoot biomass is considered a relevant component for crop yield, but relationships between biological productivity and grain yield in legume crops are usually difficult to establish. Two field experiments were carried out to investigate the relationships between grain yield, biomass production and N and P accumulation at reproductive stages of common bean (Phaseolus vulgaris) cultivars. Nine and 18 cultivars were grown on 16 m² plots in 1998 and 1999, respectively, with four replications. Crop biomass was sampled at four growth stages (flowering R6, pod setting R7, beginning of pod filling R8, and mid-pod filling R8.5), grain yield was measured at maturity, and N and P concentrations were determined in plant tissues. In both years, bean cultivars differed in grain yield, in root mass at R6 and R7 stages, and in shoot mass at R6 and R8.5, whereas at R7 and R8 differences in shoot mass were significant in 1998 only. In both years, grain yield did not correlate with shoot mass at R6 and R7 and with root mass at R6. Grain yield correlated with shoot mass at R8 in 1999 but not in 1998, with shoot mass at R8.5 and with root mass at R7 in both years. Path coefficient analysis indicated that shoot mass at R8.5 had a direct effect on grain yield in both years, that root mass at R7 had a direct effect on grain yield in 1998, and that in 1999 the amounts of N and P in shoots at R8.5 had indirect effects on grain yield via shoot mass at R8.5. A combined analysis of both experiments revealed that biomass accumulation, N and P in shoots at R6 and R7 as well as root mass at R6 were similar in both years. In 1998 however bean accumulated more root mass at R7 and more biomass and N and P in shoots at R8 and R8.5, resulting in a 57 % higher grain yield in 1998. This indicates that grain yield of different common bean cultivars is not intrinsically associated with vegetative vigor at flowering and that mechanisms during pod filling can strongly influence the final crop yield. The establishment of a profuse root system during pod setting, associated with the continuous N and P acquisition during early pod filling, seems to be relevant for higher grain yields of common bean.

2011 Road Use Tax Fund (RUTF) Study A report to the Iowa Legislature, per 2011 Iowa Code Section 307.31

The transportation system is in demand 24/7 and 365 days a year irrespective of neither the weather nor the conditions. Iowa’s transportation system is an integral and essential part of society serving commerce and daily functions of all Iowans across the state. A high quality transportation system serves as the artery for economic activity and, the condition of the infrastructure is a key element for our future growth opportunities. A key component of Iowa’s transportation system is the public roadway system owned and maintained by the state, cities and counties. In order to regularly re-evaluate the conditions of Iowa’s public roadway infrastructure and assess the ability of existing revenues to meet the needs of the system, the Iowa Department of Transportation’s 2006 Road Use Tax Fund (RUTF) report to the legislature included a recommendation that a study be conducted every five years. That recommendation was included in legislation adopted in 2007 and signed into law. The law specifically requires the following (2011 Iowa Code Section 307.31): •“The department shall periodically review the current revenue levels of the road use tax fund and the sufficiency of those revenues for the projected construction and maintenance needs of city, county, and state governments in the future. The department shall submit a written report to the general assembly regarding its findings by December 31 every five years, beginning in 2011. The report may include recommendations concerning funding levels needed to support the future mobility and accessibility for users of Iowa's public road system.” •“The department shall evaluate alternative funding sources for road maintenance and construction and report to the general assembly at least every five years on the advantages and disadvantages and the viability of alternative funding mechanisms.” Consistent with this requirement, the Iowa Department of Transportation (DOT) has prepared this study. Recognizing the importance of actively engaging with the public and transportation stakeholders in any discussion of public roadway conditions and needs, Governor Terry E. Branstad announced on March 8, 2011, the creation of, and appointments to, the Governor’s Transportation 2020 Citizen Advisory Commission (CAC). The CAC was tasked with assisting the Iowa DOT as they assess the condition of Iowa’s roadway system and evaluate current and future funding available to best address system needs. In particular the CAC was directed to gather input from the public and stakeholders regarding the condition of Iowa’s public roadway system, the impact of that system, whether additional funding is needed to maintain/improve the system, and, if so, what funding mechanisms ought to be considered. With this input, the CAC prepared a report and recommendations that were presented to Governor Branstad and the Iowa DOT in November 2011 for use in the development of this study. The CAC’s report is available at www.iowadot.gov/transportation2020/pdfs/CAC%20REPORT%20FINAL%20110211.pdf. The CAC’s report was developed utilizing analysis and information from the Iowa DOT. Therefore, the report forms the basis for this study and the two documents are very similar. Iowa is fortunate to have an extensive public roadway system that provides access to all areas of the state and facilitates the efficient movement of goods and people. However, it is also a tremendous challenge for the state, cities and counties to maintain and improve this system given flattening revenue, lost buying power, changing demands on the system, severe weather, and an aging system. This challenge didn’t appear overnight and for the last decade many studies have been completed to look into the situation and the legislature has taken significant action to begin addressing the situation. In addition, the Iowa DOT and Iowa’s cities and counties have worked jointly and independently to increase efficiency and streamline operations. All of these actions have been successful and resulted in significant changes; however, it is apparent much more needs to be done. A well-maintained, high-quality transportation system reduces transportation costs and provides consistent and reliable service. These are all factors that are critical in the evaluation companies undertake when deciding where to expand or locate new developments. The CAC and Iowa DOT heard from many Iowans that additional investment in Iowa’s roadway system is vital to support existing jobs and continued job creation in the state of Iowa. Beginning June 2011, the CAC met regularly to review material and discuss potential recommendations to address Iowa’s roadway funding challenges. This effort included extensive public outreach with meetings held in seven locations across Iowa and through a Transportation 2020 website hosted by the Iowa DOT (www.iowadot.gov/transportation2020). Over 500 people attended the public meetings held through the months of August and September, with 198 providing verbal or written comment at the meetings or through the website. Comments were received from a wide array of individuals. The public comments demonstrated overwhelming support for increased funding for Iowa’s roads. Through the public input process, several guiding principles were established to guide the development of recommendations. Those guiding principles are: • Additional revenues are restricted for road and bridge improvements only, like 95 percent of the current state road revenue is currently. This includes the fuel tax and registration fees. • State and local governments continue to streamline and become more efficient, both individually and by looking for ways to do things collectively. • User fee concept is preserved, where those who use the roads pay for them, including non¬residents. • Revenue-generating methods equitable across users. • Increase revenue generating mechanisms that are viable now but begin to implement and set the stage for longer-term solutions that bring equity and stability to road funding. • Continue Iowa’s long standing tradition of state roadway financing coming from pay-as-you-go financing. Iowa must not fall into the situation that other states are currently facing where the majority of their new program dollars are utilized to pay the debt service of past bonding. Based on the analysis of Iowa’s public roadway needs and revenue and the extensive work of the Governor’s Transportation 2020 Citizen Advisory Commission, the Iowa DOT has identified specific recommendations. The recommendations follow very closely the recommendations of the CAC (CAC recommendations from their report are repeated in Appendix B). Following is a summary of the recommendations which are fully documented beginning on page 21. 1. Through a combination of efficiency savings and increased revenue, a minimum of $215 million of revenue per year should be generated to meet Iowa’s critical roadway needs. 2. The Code of Iowa should be changed to require the study of the sufficiency of the state’s road funds to meet the road system’s needs every two years instead of every five years to coincide with the biennial legislative budget appropriation schedule. 3.Modify the current registration fee for electric vehicles to be based on weight and value using the same formula that applies to most passenger vehicles. 4.Consistent with existing Code of Iowa requirements, new funding should go to the TIME-21 Fund up to the cap ($225 million) and remaining new funding should be distributed consistent with the Road Use Tax Fund distribution formula. 5.The CAC recommended the Iowa DOT at least annually convene meetings with cities and counties to review the operation, maintenance and improvement of Iowa’s public roadway system to identify ways to jointly increase efficiency. In direct response to this recommendation, Governor Branstad directed the Iowa DOT to begin this effort immediately with a target of identifying $50 million of efficiency savings that can be captured from the over $1 billion of state revenue already provided to the Iowa DOT and Iowa’s cities and counties to administer, maintain and improve Iowa’s public roadway system. This would build upon past joint and individual actions that have reduced administrative costs and resulted in increased funding for improvement of Iowa’s public roadway system. Efficiency actions should be quantified, measured and reported to the public on a regular basis. 6.By June 30, 2012, Iowa DOT should complete a study of vehicles and equipment that use Iowa’s public roadway system but pay no user fees or substantially lower user fees than other vehicles and equipment.

Iowa Department of Transportation Fiscal Year 2011 Report of Savings by Using Video Conferencing Through Iowa Communications Network to the Iowa General Assembly

Iowa Code section 8D.10 requires certain state agencies prepare an annual report to the General Assembly certifying the identified savings associated with that state agency’s use of the Iowa Communications Network (ICN). This report covers estimated cost savings related to video conferencing via ICN for the Iowa Department of Transportation (Iowa DOT). In fiscal year 2011, the Iowa DOT did not conduct any sessions utilizing ICN’s video conferencing system, therefore, no cost savings were calculated for this report.

Failure of surgical treatment in 115 infected total hip arthroplasties - analysis of a 12-year prosthetic joint cohort study (1999-2010)

Infection of total hip arthroplasties (THA) leads to significant long-termmorbidity and high healthcare costs. We evaluated the differentreasons for treatment failure using different surgical modalities in a12-year prosthetic joint infection cohort study.Method: All patients hospitalized at our institution with infected THAwere included either retrospectively (1999-2007) or prospectively(2008-2010). THA infection was defined as growth of the same microorganismin ≥2 tissue or synovial fluid culture, visible purulence, sinustract or acute inflammation on tissue histopathology. Outcome analysiswas performed at outpatient visits, followed by contacting patients,their relatives and/or treating physicians afterwards.Results: During the study period, 117 patients with THA were identified.We exclude 2 patients due to missing data. The median age was69 years (range, 33-102 years); 42% were women. THA was mainlyperformed for osteoarthritis (n = 84), followed by trauma (n = 22),necrosis (n = 4), dysplasia (n = 2), rheumatoid arthritis (n = 1), osteosarcoma(n = 1) and tuberculosis (n = 1). 28 infections occurred early(≤3 months), 25 delayed (3-24 months) and 63 late (≥24 months aftersurgery). Infected THA were treated with (i) two-stage exchange in59 patients (51%, cure rate: 93%), (ii) one-stage exchange in 5 (4.3%,cure rate: 100%), (iii) debridement with change of mobile parts in18 (17%, cure rate: 83%), (iv) debridement without change of mobileparts in 17 (14%, cure rate: 53% ), (v) Girdlestone in 13 (11%, curerate: 100%), and (vi) two-stage exchange followed by removal in 3(2.6%). Patients were followed for a mean of 3.9 years (range, 0.1 to 9years), 7 patients died unrelated to the infected THA. 15 patients (13%)needed additional operations, 1 for mechanical reasons (dislocationof spacer) and 14 for persistent infection: 11 treated with debridementand retention (8 without change and 3 with change of mobile parts)and 3 with two-stage exchange. The mean number of surgery was 2.2(range, 1 to 5). The infection was finally eradicated in all patients, butthe functional outcome remained unsatisfactory in 20% (persistentpain or impaired mobility due to spacer or Girdlestone situation).Conclusions: Non-respect of current treatment concept leads totreatment failure with subsequent operations. Precise analysis of eachtreatment failures can be used for improving the treatment algorithmleading to better results.

Forms and accumulation of copper and zinc in a sandy typic hapludalf soil after long-term application of pig slurry and deep litter

Successive applications of pig slurry and pig deep litter may lead to an accumulation of copper (Cu) and zinc (Zn) fractions in the soil profile. The objective of this study was to evaluate the Cu and Zn forms and accumulation in a Sandy Typic Hapludalf soil after long-term application of pig slurry and deep litter. In March 2010, eight years after initiating an experiment in Braço do Norte, Santa Catarina (SC), Brazil, on a Sandy Typic Hapludalf soil, soil samples were collected from the 0-2.5, 2.5-5.0, 5-10 and 10-15 cm layers in treatments consisting of no manure application (control) and with applications of pig slurry and deep litter at two levels: the single and double rate of N requirement for maize and black oat succession. The soil was dried, ground in an agate mortar and analyzed for Cu and Zn contents by 0.01 mol L-1 EDTA and chemically fractionated to determine Cu and Zn. The applications of Pig deep litter and slurry at doses equivalent to 90 kg ha-1 N increased the contents of available Cu and Zn in the surface soil layer, if the double of this dose was applied in pig deep litter or double this dose in pig slurry, Cu and Zn migrated to a depth of 15 cm. Copper is accumulated mainly in the organic and residual fractions, and zinc preferentially in the fraction linked to clay minerals, especially in the surface soil layers.

Accumulation of phosphorus fractions and contamination potential in vineyard soils in the southern region of the state of Santa Catarina, Brazil

In vineyards, if phosphate is applied both before planting and at intervals during growth without consideration of technical criteria, the soil P fractions may be increased and their proportions altered. This study was carried out to evaluate the accumulation of P fractions and the parameters of the adsorption isotherm in a sandy Typic Hapludalf soil in vineyards with a history of successive and excessive phosphate fertilization. In December 2010, two vineyards were selected, one 4 and the other 15 years old, in Urussanga, State of Santa Catarina (Brazil). Three trenches were dug in each area and soil was collected from the 0-5, 5-10 and 10-20 cm depth ranges. The soil samples were dried in a forced-air oven, sieved and subjected to chemical analyses, P chemical fractionation and P adsorption isotherms. Excessive phosphate fertilization, before and during cultivation, particularly in the older vineyard and, consequently, with a longer history of phosphate fertilization, increased the inorganic P concentrations to the depth of 20 cm, especially in labile fractions extracted by anion exchange resin and NaHCO3 in the non-labile fraction, as well as in the non-labile fraction extracted by 1.0 mol L-1 HCl. The application of phosphate fertilizers and the long cultivation period increased the P levels in the organic labile fraction extracted by 0.5 mol L-1 NaHCO3, and especially in the moderately labile fraction extracted by 0.1 and 0.5 mol L-1 NaOH. Phosphate fertilization of older vineyards, i.e., cultivated for 15 years, increased the amounts of P desorbed in water, indicating a risk of contamination of surface waters and groundwater. The phosphate fertilization before planting, without considering the results of soil analysis, and during cultivation, disregarding the results of soil analysis, leaf analysis and expected yield, led to a reduction in the maximum P adsorption capacity in the 0-5 cm layer of vineyard 2, indicating saturation of part of the reactive particle adsorption sites.

Genotypic variability in seed accumulation of foliar-applied molybdenum to common bean

The genotypic variability in molybdenum (Mo) accumulation in common bean seeds has been demonstrated in cases in which soil is the main Mo source, but this variability is yet unknown when Mo is foliar-applied. Therefore, seed Mo concentrations (SMoCc) and seed Mo contents (SMoCt) of 12 genotypes were determined in four experiments in the Zona da Mata, Minas Gerais, Brazil, in which plants were sprayed with 600 g ha-1 Mo. For comparison, two additional experiments without external Mo were conducted. Without Mo application, the average SMoCc was undetectable or 2.83 µg g-1, without significant differences among genotypes. On average, with Mo applications, SMoCc ranged from 14.7 to 25.0 µg g-1 and SMoCt, from 3.94 to 6.84 µg. 'Majestoso' was among the genotypes with the highest SMoCc in the four experiments. However, the large-seeded 'Jalo MG-65' and 'Carnaval' generally had higher SMoCt than the small-seeded 'Majestoso'. 'Ouro Negro' and especially 'Valente' were among the genotypes with the lowest SMoCc and SMoCt. The values of these variables were 61 and 90 %, respectively, higher for 'Majestoso' than those for 'Valente'. Our results suggest that common bean genotypes differ in their capacity to accumulate foliar-applied Mo in the seeds. Mo-rich seeds of large-seeded genotypes or of small-seeded of small-seeded genotypes with good capacity to accumulate Mo in seeds can be produced with relatively less Mo fertilizer.

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis. Results of a 2-year study.

A Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (mu FEA), over 2 years, in postmenopausal osteoporotic women.Introduction Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk.Methods Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers.Results In the intention-to-treat population (n = 83, age: 64 +/- 8 years; lumbar T-score: -2.8 +/- 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (-0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (-1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated.Conclusions Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

The accumulation of reproductive incompatibilities in African cichlid fish.

The rate at which different components of reproductive isolation accumulate with divergence time between species has only been studied in a limited, but growing, number of species. We measured premating isolation and hybrid inviability at four different ontogenetic stages from zygotes to adults in interspecific hybrids of 26 pairs of African cichlid species, spanning the entire East African haplochromine radiation. We then used multiple relaxed molecular clock calibrations to translate genetic distances into absolute ages to compare evolutionary rates of different components of reproductive isolation. We find that premating isolation accumulates fast initially but then changes little with increasing genetic distance between species. In contrast, postmating isolation between closely related species is negligible but then accumulates rapidly, resulting in complete hybrid inviability after 4.4/8.5/18.4 million years (my). Thus, the rate at which complete intrinsic incompatibilities arise in this system is orders of magnitude lower than rates of speciation within individual lake radiations. Together these results suggest divergent ecological adaptations may prevent populations from interbreeding and help maintain cichlid species diversity, which may be vulnerable to environmental degradation. By quantifying the capacity to produce viable hybrids between allopatric, distantly related lineages our results also provide an upper divergence time limit for the "hybrid swarm origin" model of adaptive radiation.