The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment.

Species-Specific Relationships between Water Transparency and Male Coloration within and between Two Closely Related Lake Victoria Cichlid Species

Environmental variation in signalling conditions affects animal communication traits, with possible consequences for sexual selection and reproductive isolation. Using spectrophotometry, we studied how male coloration within and between populations of two closely related Lake Victoria cichlid species (Pundamilia pundamilia and P. nyererei) covaries with water transparency. Focusing on coloration patches implicated in sexual selection, we predicted that in clear waters, with broad-spectrum light, (1) colours should become more saturated and (2) shift in hue away from the dominant ambient wavelengths, compared to more turbid waters. We found support for these predictions for the red and yellow coloration of P. nyererei but not the blue coloration of P. pundamilia. This may be explained by the species difference in depth distribution, which generates a steeper gradient in visual conditions for P. nyererei compared to P. pundamilia. Alternatively, the importance of male coloration in intraspecific sexual selection may differ between the species. We also found that anal fin spots, that is, the orange spots on male haplochromine anal fins that presumably mimic eggs, covaried with water transparency in a similar way for both species. This is in contrast to the other body regions studied and suggests that, while indeed functioning as signals, these spots may not play a role in species differentiation.

Evaluating the Trade-off Between Energy Efficiency and QoE in Wireless Mesh Networks

The increasing usage of wireless networks creates new challenges for wireless access providers. On the one hand, providers want to satisfy the user demands but on the other hand, they try to reduce the operational costs by decreasing the energy consumption. In this paper, we evaluate the trade-off between energy efficiency and quality of experience for a wireless mesh testbed. The results show that by intelligent service control, resources can be better utilized and energy can be saved by reducing the number of active network components. However, care has to be taken because the channel bandwidth varies in wireless networks. In the second part of the paper, we analyze the trade-off between energy efficiency and quality of experience at the end user. The results reveal that a provider's service control measures do not only reduce the operational costs of the network but also bring a second benefit: they help maximize the battery lifetime of the end-user device.

The Validation of a New Visual Anaemia Evaluation Tool HemoHue HH1 in Patients with End-Stage Renal Disease

In chronic haemodialysis patients, anaemia is a frequent finding associated with high therapeutic costs and further expenses resulting from serial laboratory measurements. HemoHue HH1, HemoHue Ltd, is a novel tool consisting of a visual scale for the noninvasive assessment of anaemia by matching the coloration of the conjunctiva with a calibrated hue scale. The aim of the study was to investigate the usefulness of HemoHue in estimating individual haemoglobin concentrations and binary treatment outcomes in haemodialysis patients. A prospective blinded study with 80 hemodialysis patients comparing the visual haemoglobin assessment with the standard laboratory measurement was performed. Each patient's haemoglobin concentration was estimated by seven different medical and nonmedical observers with variable degrees of clinical experience on two different occasions. The estimated population mean was close to the measured one (11.06 ± 1.67 versus 11.32 ± 1.23 g/dL, P < 0.0005). A learning effect could be detected. Relative errors in individual estimates reached, however, up to 50%. Insufficient performance in predicting binary outcomes (ROC AUC: 0.72 to 0.78) and poor interrater reliability (Kappa < 0.6) further characterised this method.

Vorlanite, (CaU6+)O4, from Jabel Harmun, Palestinian Autonomy, Israel

Vorlanite (CaU6+)O4 Fm3̄m, a = 5.3647(9) Å, V = 154.40(4) Å3, Z = 2 was found in larnite pyrometamorphic rocks of the Hatrurim formation at the Jabel Harmun locality, Judean Desert, Palestinian Autonomy. Vorlanite crystals from these larnite rocks are dark-gray with greenish hue in transmitted light. This color in transmitted light is in contrast to dark-red vorlanite Fm3̄m, a = 5.3813(2) Å, V = 155.834(10)Å3, Z = 2 from the type locality Upper Chegem caldera, Northern Caucasus. Heating above 750 °C of dark-gray vorlanite from the Jabel Harmun, as well as dark-red vorlanite from Caucasus, led to formation of yellow trigonal uranate CaUO4. The unusual color of vorlanite from Jabel Harmun is assumed to be related to small impurities of tetravalent uranium.

Female preference for male color is necessary and sufficient for assortative mating in 2 cichlid sister species

A critical step for speciation in the face of gene flow is the origination of reproductive isolation. The evolution of assortative mating greatly facilitates this process. Assortative mating can be mediated by one or multiple cues across an array of sensory modalities. We here explore possible cues that may underlie female mate choice in a sympatric species pair of cichlid fish from Lake Victoria, Pundamilia pundamilia and Pundamilia nyererei. Previous studies identified species-specific female preferences for male coloration, but effects of other cues could not be ruled out. Therefore, we assessed female choice in a series of experiments in which we manipulated visual (color) and chemical cues. We show that the visibility of differences in nuptial hue (i.e., either blue or red) between males of the 2 species is necessary and sufficient for assortative mating by female mate choice. Such assortment mediated by a single cue may evolve relatively quickly, but could make reproductive isolation vulnerable to environmental changes. These findings confirm the important role of female mate choice for male nuptial hue in promoting the explosive speciation of African haplochromine cichlids.

Subgingival microbiota of Sri Lankan tea labourers naïve to oral hygiene measures.

AIM To characterize the subgingival microbiota within a cohort of adult males (n = 32) naïve to oral hygiene practices, and to compare the composition of bacterial taxa present in periodontal sites with various probing depths. MATERIAL AND METHODS Subgingival plaque samples were collected from single shallow pocket [pocket probing depth (PPD)≤3 mm] and deep pocket (PPD≥6 mm) sites from each subject. A polymerase chain reaction based strategy was used to construct a clone library of 16S ribosomal RNA (rRNA) genes for each site. The sequences of ca. 30-60 plasmid clones were determined for each site to identify resident taxa. Microbial composition was compared using a variety of statistical and bioinformatics approaches. RESULTS A total of 1887 cloned 16S rRNA gene sequences were analysed, which were assigned to 318 operational taxonomic units (98% identity cut-off). The subgingival microbiota was dominated by Firmicutes (69.8%), Proteobacteria (16.3%), and Fusobacteria (8.0%). The overall composition of microbial communities in shallow sites was significantly different from those within deep sites (∫-Libshuff, p < 0.001). CONCLUSIONS A taxonomically diverse subgingival microbiota was present within this cohort; however, the structures of the microbial communities present in the respective subjects exhibited limited variation. Deep and shallow sites contained notably different microbial compositions, but this was not correlated with the rate of periodontal progression.

The Effect of 6 versus 9 Years of Zoledronic Acid Treatment in Osteoporosis: A Randomized Second Extension to the HORIZON-Pivotal Fracture Trial (PFT).

While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n=95) and Z6P3 (n=95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p=0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. This article is protected by copyright. All rights reserved.

Evolution of colour patterns in East African cichlid fish

African cichlid fishes have undergone outbursts of explosive speciation in several lakes, accompanied by rapid radiations in coloration and ecology. Little is known about the evolutionary forces that triggered these events but a hypothesis, published by Wallace Dominey in 1984, has figured prominently. It states that the evolution of colour patterns is driven by sexual selection and that these colour patterns are important in interspecific mate choice, a combination which holds the potential for rapid speciation. Here we present phylogenetic analyses that describe major events in colour evolution and test predictions yielded by Dominey's hypothesis. We assembled information on stripe patterns and the presence or absence of nuptial coloration from more than 700 cichlid species representing more than 90 taxa for which molecular phylogenetic hypotheses were available. We show that sexual selection is most likely the selection force that made male nuptial coloration arise and evolve quickly. In contrast, stripe patterns, though phylogenetically not conserved either, are constrained ecologically. The evolution of vertical bar patterns is associated with structurally complex habitats, such as rocky substrates or vegetation. The evolution of a horizontal stripe is associated with a piscivorous feeding mode. Horizontal stripes are also associated with shoaling behaviour. Strength of sexual selection, measured in terms of the mating system (weak in monogamous, strong in promiscuous species), has no detectable effects on stripe pattern evolution. In promiscuous species the frequency of difference between sister species in nuptial hue is higher than in pair bonding and harem forming species, but the frequency of difference in stripe pattern is lower. We argue that differences between the two components of coloration in their exposure to natural selection explain their very different evolutionary behaviour. Finally, we suggest that habitat-mediated selection upon chromomotor flexibility, a special form of phenotypic plasticity found in the river-dwelling outgroups of the lake-dwelling cichlids, explains the rapid and recurrent ecology-associated radiation of stripe patterns in lake environments, a new hypothesis that yields experimentally testable predictions.

Can ancient colour polymorphisms explain why some cichlid lineages speciate rapidly under disruptive sexual selection?

It is not sufficiently understood why some lineages of cichlid fishes have proliferated in the Great Lakes of East Africa much more than anywhere else in the world, and much faster than other cichlid lineages or any other group of freshwater fish. Recent field and experimental work on Lake Victoria haplochromines suggests that mate choice-mediated disruptive sexual selection on coloration, that can cause speciation even in the absence of geographical isolation, may explain it. We summarize the evidence and propose a hypothesis for the genetics of coloration that may help understand the phenomenon. By detl ning colour patterns by hue and arrangement of hues on the body, we could assign almost all observed phenotypes of Lake Victoria cichlids to one of three female («plain», «orange blotched», «black and white») and three male («blue», «red-ventrum», «reddorsum») colour patterns. These patterns diagnose species but frequently eo-occur also as morphs within the same population, where they are associated with variation in mate preferences, and appear to be transient stages in speciation. Particularly the male patterns occur in almost every genus of the species flock. We propose that the patterns and their association into polymorphisms express an ancestral trait that is retained across speciation. Our model for male colour pattern assumes two structural loci. When both are switched off, the body is blue. When switched on by a cascade of polymorphic regulatory genes, one expresses a yellow to red ventrum, the other one a yellow to red dorsum. The expression of colour variation initiates speciation. The blue daughter species will inherit the variation at the regulatory genes that can, without new mutational events, purely by recombination, again expose the colour polymorphism, starting the process anew. Very similar colour patterns also dominate among the Mbuna of Lake Malawi. In contrast, similar colour polymorphisms do not exist in the lineages that have not proliferated in the Great Lakes. The colour pattern polymorphism may be an ancient trait in the lineage (or lineages) that gave rise to the two large haplochromine radiations. We propose two tests of our hypothesis.

A novel colourimetric technique to assess chewing function using two-coloured specimens: Validation and application

OBJECTIVES Chewing efficiency may be evaluated using cohesive specimen, especially in elderly or dysphagic patients. The aim of this study was to evaluate three two-coloured chewing gums for a colour-mixing ability test and to validate a new purpose built software (ViewGum©). METHODS Dentate participants (dentate-group) and edentulous patients with mandibular two-implant overdentures (IOD-group) were recruited. First, the dentate-group chewed three different types of two-coloured gum (gum1-gum3) for 5, 10, 20, 30 and 50 chewing cycles. Subsequently the number of chewing cycles with the highest intra- and inter-rater agreement was determined visually by applying a scale (SA) and opto-electronically (ViewGum©, Bland-Altman analysis). The ViewGum© software determines semi-automatically the variance of hue (VOH); inadequate mixing presents with larger VOH than complete mixing. Secondly, the dentate-group and the IOD-group were compared. RESULTS The dentate-group comprised 20 participants (10 female, 30.3±6.7 years); the IOD-group 15 participants (10 female, 74.6±8.3 years). Intra-rater and inter-rater agreement (SA) was very high at 20 chewing cycles (95.00-98.75%). Gums 1-3 showed different colour-mixing characteristics as a function of chewing cycles, gum1 showed a logarithmic association; gum2 and gum3 demonstrated more linear behaviours. However, the number of chewing cycles could be predicted in all specimens from VOH (all p<0.0001, mixed linear regression models). Both analyses proved discriminative to the dental state. CONCLUSION ViewGum© proved to be a reliable and discriminative tool to opto-electronically assess chewing efficiency, given an elastic specimen is chewed for 20 cycles and could be recommended for the evaluation of chewing efficiency in a clinical and research setting. CLINICAL SIGNIFICANCE Chewing is a complex function of the oro-facial structures and the central nervous system. The application of the proposed assessments of the chewing function in geriatrics or special care dentistry could help visualising oro-functional or dental comorbidities in dysphagic patients or those suffering from protein-energy malnutrition.

Relationships between soil nitrate desorbed from anion-exchange membranes, canopy reflectance and nitrate leaching losses from cool-season lawn turf.

Nutrient leaching studies are expensive and require expertise in water collection and analyses. Less expensive or easier methods that estimate leaching losses would be desirable. The objective of this study was to determine if anion-exchange membranes (AEMs) and reflectance meters could predict nitrate (NO3-N) leaching losses from a cool-season lawn turf. A two-year field study used an established 90% Kentucky bluegrass (Poa pratensis L.)-10% creeping red fescue (Festuca rubra L.) turf that received 0 to 98 kg N ha-1 month-1, from May through November. Soil monolith lysimeters collected leachate that was analyzed for NO3-N concentration. Soil NO3-N was estimated with AEMs. Spectral reflectance measurements of the turf were obtained with chlorophyll and chroma meters. No significant (p > 0.05) increase in percolate flow-weighted NO3-N concentration (FWC) or mass loss occurred when AEM desorbed soil NO3-N was below 0.84 µg cm-2 d-1. A linear increase in FWC and mass loss (p < 0.0001) occurred, however, when AEM soil NO3-N was above this value. The maximum contaminant level (MCL) for drinking water (10 mg L-1 NO3-N) was reached with an AEM soil NO3-N value of 1.6 µg cm-2 d-1. Maximum meter readings were obtained when AEM soil NO3 N reached or exceeded 2.3 µg cm-2 d-1. As chlorophyll index and hue angle (greenness) increased, there was an increased probability of exceeding the NO3-N MCL. These data suggest that AEMs and reflectance meters can serve as tools to predict NO3-N leaching losses from cool-season lawn turf, and to provide objective guides for N fertilization.

Cool-season turfgrass color and growth calibrated to leaf nitrogen

Tissue N analysis a tool available for N management of turfgrass. However, peer-reviewed calibration studies to determine optimum tissue N values are lacking. A field experiment with a mixed cool-season species lawn and a greenhouse experiment with Kentucky bluegrass (Poa pratensis L.) were conducted across 2 yr, each with randomized complete block design. Treatments were N application rates between 0 and 587 kg N ha-1 yr-1. In the field experiment, clipping samples were taken monthly from May to September, dried, ground, and analyzed for total N. Clippings samples were collected one to two mowings after plots were fertilized. Linear plateau models comparing relative clipping yield, Commission Internationale de l' Eclairage hue, and CM1000 index to leaf N concentrations were developed. In the greenhouse experiment, clipping samples were taken every 2 wk from May to October and composited across sample dates for leaf N analysis. Color and clipping yields were related to leaf N concentrations using linear plateau models. These models indicated small marginal improvements in growth or color when leaf N exceeded 30 g kg-1, suggesting that a leaf N test can separate turf with optimum leaf N concentrations from turf with below optimum leaf N concentrations. Plateaus in leaf N concentrations with increasing N fertilizer rates suggest, however, that this test may be unable to identify sites with excess available soil N when turf has been mowed before tissue sampling.

Efecto del estado de madurez y atmósferas modificadas sobre la calidad de cerezas cv. Sweetheart

Se estudió el efecto de cosechar cerezas en dos estados de madurez, así como el uso de atmósferas modificadas empleando PBD y PVC, sobre la calidad de fruta almacenada a 0 °C durante 21 y 42 días, respectivamente. La calidad fue evaluada en base a pérdida de peso (%), color (ángulo hue), firmeza, contenido de sólidos solubles, aspecto de los pedicelos y presencia de podredumbres. La fruta cosechada más madura presentó color, sólidos solubles y firmeza adecuados durante los 21 días a 0 °C, pero el almacenamiento estuvo limitado por la deshidratación de los pedicelos, que mantuvieron aspecto comercial sólo durante una semana. Para ambos estados de madurez, la pérdida de peso fue importante y se registró aumento del contenido de sólidos solubles y firmeza. Sin embargo, la fruta cosechada más inmadura no alcanzó en ningún momento la coloración ni contenido de azúcares de la fruta cosechada en estado de madurez más avanzado. Mediante el uso de las bolsas PBD se logró minimizar la deshidratación y mantener las características organolépticas de la fruta, así como un alto porcentaje de pedicelos con buen aspecto y color durante los 42 días de conservación en frío. El uso de PVC se vio limitado por el deterioro de los pedicelos que afectó alrededor del 50 % de la fruta analizada al término de la primera semana.

Influencia del tiempo de maceración sobre el color, la composición tánica y la astringencia de vinos Cabernet Sauvignon y Malbec de Argentina

El objetivo fue determinar qué tiempo de maceración permite una mayor expresión del color y del cuerpo y una menor astringencia en vinos Cabernet Sauvignon (CS) y Malbec (M), de Mendoza, Argentina. A partir de dos vinificaciones industriales de 20 000 L se llevó a cabo un experimento (n = 3) probando tres tiempos de maceración: 5, 10 y 20 días, mediante sucesivos descubes de 60 L. En los vinos resultantes se determinaron fenoles totales, taninos condensados totales, índice de gelatina, intensidad colorante, matiz, color copigmentado y color polimérico, mediante técnicas de espectrofotometría VIS y UV. Los vinos fueron evaluados por un panel de degustadores expertos. Los CS obtenidos con maceración de 10 y 20 días fueron similares y resultaron superiores a los de 5 días en contenidos de antocianos, color polimérico y taninos. También provocaron sensaciones de concentración y untuosidad mayores. Además resultaron más ásperos, astringentes y secantes que los de 5 días, pero estas sensaciones no alcanzaron notas elevadas. Los vinos CS de 20 días alcanzaron contenidos de polifenoles totales y de taninos no precipitables con gelatina mayores que los CS de 10 días. Los vinos M de 10 lograron mayores intensidades colorantes, polifenoles tales, antocianos, color polimérico y taninos que los de 5 y 20 días. Esto se asoció con sensaciones de concentración y untuosidad intensas y similares a las de los CS de 10 y 20 días pero con menos aspereza, astringencia y secante. Los M de 5 días resultaron muy pobres en atributos y los de 20 días con características intermedias entre los M de 5 y los M de 10 días. Tomando en cuenta las dos variedades y los tres tiempos de maceración, cuanto mayor fue el tiempo de maceración menor fue la proporción de antocianos copigmentados y mayor la de antocianos polimerizados. Los polifenoles totales y los taninos se correlacionaron positivamente con la aspereza, la astringencia, lo secante, la untuosidad y la concentración. Lo secante se asoció negativamente con la proporción de taninos no precipitables con gelatina.