•ET/HT is first choice for osteoporosis prevention in women <10 years of menopause.•Bisphosphonates is first choice for osteoporosis in older women ≥60 years.•SERMs are an alternative for women who ...cannot take bisphosphonates or HT/ET.
In the beginning, that is from the 1960's, when a link between menopause and osteoporosis was first identified; estrogen treatment was the standard for preventing bone loss, however there was no fracture data, even though it was thought to be effective. This continued until the Women's Health Initiative (WHI) study in 2001 that published data on 6 years of treatment with hormone therapy that showed an increase in heart attacks and breast cancer. Even though the risks were small, 1 per 1500 users annually, patients were worried and there was a large drop off in estrogen use. In later analyses the WHI study showed that estrogen reduced fractures and actually prevented heart attacks in the 50–60 year age group. Estrogen alone appeared to be safer to use than estrogen+the progestin medroxyprogesterone acetate and actually reduced breast cancer.
At the same time other drugs were being developed for bone that belong to the bisphosphonate group and the first generation of compounds showed moderate potency on bone resorption. The second and third generation compounds were much more potent and in a series of large trials were shown to reduce fractures. For the last 15 years the treatment of osteoporosis belonged to the bisphosphonate compounds, most of which reduce fracture rates by 50 percent. With the exception of gastrointestinal irritation the drugs are well tolerated and highly effective. The sophistication of the delivery systems now allow treatment that can be given daily, weekly, monthly and annually either orally or intravenously.
Bone remodeling is a dynamic process that repairs microfractures and replaces old bone with new bone. In the last 10 years there has been a remarkable understanding of bone biology so that new therapies can be specifically designed on a biological basis. The realization that RANKL was the final cytokine involved in the resorption process and that marrow cells produced a natural antagonist called Osteoprotegerin (OPG) quickly led to two lines of therapy. First OPG was used as a therapy to block RANKL was initially successful but later antibodies against OPG developed and this line of treatment had to be discontinued. The next step was to develop a monoclonal antibody against RANKL and this proved to be highly effective in blocking bone resorption. It led to development of a drug Denosumab that successfully reduces fractures and is now one of the therapeutic options for osteoporosis treatment.
On the anabolic side bone biology research showed that osteocytes produces sclerostin an inhibitor of the anabolic WNT signaling pathway. Recent development of a monoclonal antibody against sclerostin has shown remarkable anabolic activity in bone showing large increases in bone density and fracture trials are now underway. The newer treatments for osteoporosis are likely to be based on our understanding of bone biology and the design of new highly specific compounds with fewer side effects.
This review summarizes the diagnosis of postmenopausal osteoporosis and various available non-pharmacological and pharmacological therapies available for its management. This article is part of a Special Issue entitled ‘Menopause’.
Personal measurement studies and modelling investigations are used to examine pollutant exposure for pedestrians in the urban environment: each presenting various strengths and weaknesses in relation ...to labour and equipment costs, a sufficient sampling period and the accuracy of results. This modelling exercise considers the potential benefits of modelling results over personal measurement studies and aims to demonstrate how variations in fleet composition affects exposure results (presented as mean concentrations along the centre of both footpaths) in different traffic scenarios. A model of Pearse Street in Dublin, Ireland was developed by combining a computational fluid dynamic (CFD) model and a semi-empirical equation to simulate pollutant dispersion in the street. Using local NOx concentrations, traffic and meteorological data from a two-week period in 2011, the model were validated and a good fit was presented. To explore the long-term variations in personal exposure due to variations in fleet composition, synthesised traffic data was used to compare short-term personal exposure data (over a two-week period) with the results for an extended one-year period. Personal exposure during the two-week period underestimated the one-year results by between 8% and 65% on adjacent footpaths. The findings demonstrate the potential for relative differences in pedestrian exposure to exist between the north and south footpaths due to changing wind conditions in both peak and off-peak traffic scenarios. This modelling approach may help overcome potential under- or over-estimations of concentrations in personal measurement studies on the footpaths. Further research aims to measure pollutant concentrations on adjacent footpaths in different traffic and wind conditions and to develop a simpler modelling system to identify pollutant hotspots on our city footpaths so that urban planners can implement improvement strategies to improve urban air quality.
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•Examine air quality by combining a CFD model and semi-empirical equation•The distribution of traffic between lanes impacts upon air quality on the footpaths.•Predominant wind direction and speed needs to be accounted for in sampling studies.•Short-term results may over- or under-estimate personal exposure in street canyons.•Personal exposure results vary on adjacent footpaths throughout the day.
Vitamin D and aging Gallagher, J Christopher
Endocrinology and metabolism clinics of North America,
06/2013, Letnik:
42, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Age-related changes affect vitamin D metabolism and increase the requirement for vitamin D in the elderly. Also there is an age related decrease in calcium absorption and a higher calcium intake is ...needed. Increasing calcium from dietary sources may be better than supplements, and requires increasing the intake of dairy products or other and calcium-fortified foods. Evidence suggests that vitamin D and calcium nutrition can be improved in the elderly by increasing the vitamin D intake to 800 IU daily together with a total calcium intake of 1000 mg daily. This combination is a simple, inexpensive strategy that can reduce fractures in institutionalized individuals by 30%.
ABSTRACT
We present the Hubble imaging Probe of Extreme Environments and Clusters (HiPEEC) survey. We fit HST NUV to NIR broad-band and H α fluxes to derive star cluster ages, masses, and extinctions ...and determine the star formation rate (SFR) of six merging galaxies. These systems are excellent laboratories to trace cluster formation under extreme gas physical conditions, rare in the local Universe, but typical for star-forming galaxies at cosmic noon. We detect clusters with ages of 1–500 Myr and masses that exceed 107 M⊙. The recent cluster formation history and their distribution within the host galaxies suggest that systems such as NGC 34, NGC 1614, and NGC 4194 are close to their final coalescing phase, while NGC 3256, NGC 3690, and NGC 6052 are at an earlier/intermediate stage. A Bayesian analysis of the cluster mass function in the age interval 1–100 Myr provides strong evidence in four of the six galaxies that an exponentially truncated power law better describes the observed mass distributions. For two galaxies, the fits are inconclusive due to low number statistics. We determine power-law slopes β ∼ −1.5 to −2.0 and truncation masses, Mc, between 106 and a few times 107 M⊙, among the highest values reported in the literature. Advanced mergers have higher Mc than early/intermediate merger stage galaxies, suggesting rapid changes in the dense gas conditions during the merger. We compare the total stellar mass in clusters to the SFR of the galaxy, finding that these systems are among the most efficient environments to form star clusters in the local Universe.
Serum 25-hydroxyvitamin D (25-OHD) is considered the best biomarker of clinical vitamin D status.
To determine the effect of increasing oral doses of vitamin D(3) on serum 25-(OH)D and serum ...parathyroid hormone (PTH) levels in postmenopausal white women with vitamin D insufficiency (defined as a 25-OHD level ≤50 nmol/L) in the presence of adequate calcium intake. These results can be used as a guide to estimate the Recommended Dietary Allowance (RDA) (defined as meeting the needs of 97.5% of the population) for vitamin D(3).
Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00472823)
Creighton University Medical Center, Omaha, Nebraska.
163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year.
Participants were randomly assigned to receive placebo or vitamin D(3), 400, 800, 1600, 2400, 3200, 4000, or 4800 IU once daily. Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg.
The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months.
The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3). The RDA of vitamin D(3) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d. A mixed-effects model predicted that 600 IU of vitamin D(3) daily could also meet this goal. Compared with participants with a normal body mass index (<25 kg/m(2)), obese women (≥30 kg/m(2)) had a 25-(OH)D level that was 17.8 nmol/L lower. Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3) (P = 0.012). Depending on the criteria used, hypercalcemia occurred in 2.8% to 9.0% and hypercalciuria in 12.0% to 33.0% of participants; events were unrelated to dose.
Findings may not be generalizable to other age groups or persons with substantial comorbid conditions.
A vitamin D(3) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5% of women; however, a model predicted the same response with a vitamin D(3) dosage of 600 IU/d. These results can be used as a guide for the RDA of vitamin D(3), but prospective trials are needed to confirm the clinical significance of these results.
National Institute on Aging.
The giant elliptical galaxy NGC 1275, at the centre of the Perseus cluster, is surrounded by a well-known giant nebulosity of emission-line filaments, which are plausibly in excess of 10(8) years ...old. The filaments are dragged out from the centre of the galaxy by radio-emitting 'bubbles' rising buoyantly in the hot intracluster gas, before later falling back. They act as markers of the feedback process by which energy is transferred from the central massive black hole to the surrounding gas. The mechanism by which the filaments are stabilized against tidal shear and dissipation into the surrounding extremely hot (4 x 10(7) K) gas has been unclear. Here we report observations that resolve thread-like structures in the filaments. Some threads extend over 6 kpc, yet are only 70 pc wide. We conclude that magnetic fields in the threads, in pressure balance with the surrounding gas, stabilize the filaments, so allowing a large mass of cold gas to accumulate and delay star formation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present optical integral field unit (IFU) observations (VLT/VIMOS-IFU and WIYN/SparsePak), and associated archival deep Hα imaging (MPG/ESO 2.2 m WFI), of the nearby starburst galaxy NGC 253. With ...VIMOS we observed the nuclear region and southern superwind outflow in detail with five pointings, and with the WIYN/SparsePak IFU we observed two partially overlapping regions covering the central disc and northern halo. The high signal-to-noise ratio of the data and spectral resolution (80-90 km s−1) enable us to accurately decompose the emission line profiles into multiple components.
The combination of these data sets, together with the wealth of information on NGC 253 available in the literature, allows us to study the starburst-driven superwind in great detail. We investigate the known minor axis outflow cone, which is well-defined in the Hα imaging and kinematics between radii of 280 and 660 pc from the nucleus. Kinematic modelling indicates a wide opening angle (∼60°), an inclination consistent with that of the disc and deprojected outflow speeds of a few 100 km s−1 that increase with distance above the plane. The N ii/Hα and S ii/Hα line ratio maps imply that a significant fraction of the wind optical emission lines arise from shocked gas, with localized pockets/filaments of strongly shocked gas. From the kinematics, the cone appears partially closed in at least one place, and very broad Hα linewidths (>400 km s−1 full width at half maximum) suggest there is material filling the cone in some regions. Extrapolation of the cone to its apex shows it is not centred on the starburst nucleus, suggesting the wind is deflected and collimated by the dense circumnuclear material. We discuss the implications of these findings on our understanding of the origins and evolution of the superwind. No evidence for an outflow is found on the north-western side of the disc out to >2 kpc in our optical data, due to obscuration by the foreground disc. The lack of an obvious connection between the inner (r < 1 kpc) Hα and X-ray bright outflow cone and the large-scale (r≲ 10 kpc) X-ray 'horns' is also discussed.
Since the shooting of Black teenager Michael Brown by White police officer Darren Wilson in Ferguson, Missouri, the protest hashtag #BlackLivesMatter has amplified critiques of extrajudicial killings ...of Black Americans. In response to #BlackLivesMatter, other Twitter users have adopted #AllLivesMatter, a counter-protest hashtag whose content argues that equal attention should be given to all lives regardless of race. Through a multi-level analysis of over 860,000 tweets, we study how these protests and counter-protests diverge by quantifying aspects of their discourse. We find that #AllLivesMatter facilitates opposition between #BlackLivesMatter and hashtags such as #PoliceLivesMatter and #BlueLivesMatter in such a way that historically echoes the tension between Black protesters and law enforcement. In addition, we show that a significant portion of #AllLivesMatter use stems from hijacking by #BlackLivesMatter advocates. Beyond simply injecting #AllLivesMatter with #BlackLivesMatter content, these hijackers use the hashtag to directly confront the counter-protest notion of "All lives matter." Our findings suggest that Black Lives Matter movement was able to grow, exhibit diverse conversations, and avoid derailment on social media by making discussion of counter-protest opinions a central topic of #AllLivesMatter, rather than the movement itself.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Falls are a major health problem in elderly individuals. Although intensive physical therapy and management of hazards in the home can reduce falls by 25%, long-term practicality limits their use. ...Interest in vitamin D as a medical therapy has led to many trials; however, results using daily oral doses of vitamin D have been inconsistent. In the past 5 years, studies on the effect of bolus doses of vitamin D have produced surprising results. Bolus doses of vitamin D, given annually (at a dose of 300,000 IU or 500,000 IU) or monthly (at a dose of 24,000 IU or 60,000 IU) - equivalent to approximate daily doses of 800 IU, 1400 IU and 2,000 IU - result in a significant increase in the number of falls and fractures associated with serum levels of 25-hydroxyvitamin D greater than 40-45 ng/ml (equivalent to 100-112 nmol/l). These unexpected results show increased falls and fractures are adverse events related to vitamin D administration. Until further safety data is available, bolus dosing or daily doses should not exceed 3,000 IU and serum levels of 25-hydroxyvitamin D should not exceed 40-45 ng/ml (equivalent to 100-112 nmol/l) in elderly individuals.
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