The purpose of this paper is to provide a comprehensive presentation and interpretation of the Ensemble Kalman Filter (EnKF) and its numerical implementation. The EnKF has a large user group, and numerous publications have discussed applications and theoretical aspects of it. This paper reviews the important results from these studies and also presents new ideas and alternative interpretations which further explain the success of the EnKF. In addition to providing the theoretical framework needed for using the EnKF, there is also a focus on the algorithmic formulation and optimal numerical implementation. A program listing is given for some of the key subroutines. The paper also touches upon specific issues such as the use of nonlinear measurements, in situ profiles of temperature and salinity, and data which are available with high frequency in time. An ensemble based optimal interpolation (EnOI) scheme is presented as a cost-effective approach which may serve as an alternative to the EnKF in some applications. A fairly extensive discussion is devoted to the use of time correlated model errors and the estimation of model bias.

The Ensemble Kalman Filter: Theoretical formulation and practical implementation

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

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Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.

BACKGROUND
Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known.


METHODS
We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women.


RESULTS
Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001).


CONCLUSIONS
Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Vitamin D and Calcium to Prevent Hip Fractures in Elderly Women

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.

A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX.

A review of the performance of different ventilation and airflow distribution systems in buildings

Summary
In a prospective cohort study of 5,995 older American men (MrOS), users of angiotensin-converting enzyme (ACE) inhibitors had a small but significant increase in bone loss at the hip over 4 years after adjustment for confounders. Use of angiotensin II AT1 receptor blockers (ARB) was not significantly associated with bone loss.

Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men

Long-term measurements of radon progeny concentrations with solid-state nuclear track detectors

Hip fracture is associated with high morbidity, mortality, and economic burden worldwide. It is also a major risk factor for a subsequent fracture. A literature search on the management of osteoporosis in patients with hip fracture was performed on the Medline database. Only one clinical drug trial was conducted in patients with a recent hip fracture. Further studies that specifically address post-fracture management of hip fracture are needed. The efficacy of anti-osteoporosis medication in older individuals and those at high risk of fall is reviewed in this paper. Adequate nutrition is vital for bone health and to prevent falls, especially in malnourished patients. Protein, calcium, and vitamin D supplementation is associated with increased hip BMD and a reduction in falls. Fall prevention, exercise, and balance training incorporated in a comprehensive rehabilitation program are essential to improve functional disability and survival. Exclusion of secondary causes of osteoporosis and treatment of coexistent medical conditions are also vital. Such a multidisciplinary team approach to the management of hip fracture patients is associated with a better clinical outcome. Although hip fracture is the most serious of all fractures, osteoporosis management should be prioritized to prevent deterioration of health and occurrence of further fracture.

/pdf/management-of-osteoporosis-in-patients-hospitalized-for-hip-165h6zteai.pdf

Management of osteoporosis in patients hospitalized for hip fractures.

Summary
Calcaneal QUS is comparable to DXA in predicting non-vertebral fractures in older Chinese men.

Predictive values of calcaneal quantitative ultrasound and dual energy X ray absorptiometry for non-vertebral fracture in older men: results from the MrOS study (Hong Kong).

The association of trabecular bone score (TBS) with fracture risk and its added predictive value to FRAX® for clinical use have never been independently evaluated in a Chinese population. TBS may improve the predictive power of FRAX® for clinical use in older Chinese men. Trabecular bone score (TBS) of lumbar spine on Dual X-ray densitometry provides information on bone architecture. We therefore examined the additive value of TBS to FRAX® in predicting major osteoporotic fractures (MOFs) in older Chinese people. Four thousand community-dwelling Chinese men and women aged ≥65 years were followed up for fracture incidence for an average period of 9.94 and 8.82 years, respectively. At baseline, areal BMD of hip and lumbar spine were measured by DXA, TBS was estimated for the lumbar spine, and FRAX® for 10-year risk of MOFs (hip, clinical spine, shoulder, and wrist) was estimated. Cox regression model was used to evaluate the associations between TBS and FRAX® with the MOFs risk. The area under receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI), and category-based net reclassification improvement (NRI) were applied to evaluate the improved prediction ability. During the follow-up, 126 men and 215 women had at least one incident MOF. Each SD decrease in TBS was significantly associated with incident MOFs, with HR (95%CI) of 1.53 (1.30–1.80) and 1.40 (1.22–1.61) in men and women, respectively. TBS-adjusted FRAX® predicts better than FRAX® with a significantly increased AUC and IDI in men. Using specific intervention thresholds, TBS-adjusted FRAX® brings about 5 % overall correct reclassification for MOFs prediction than FRAX® in men. The increased correct MOFs risk classifications were not significant in older women. TBS-adjusted FRAX® may improve the predictive power of FRAX® on MOFs for clinical use in older Chinese men.

The added value of trabecular bone score to FRAX® to predict major osteoporotic fractures for clinical use in Chinese older people: the Mr. OS and Ms. OS cohort study in Hong Kong

J. Leung

Papers

Does the use of ACE inhibitors or angiotensin receptor blockers affect bone loss in older men

Long-term measurements of radon progeny concentrations with solid-state nuclear track detectors

Management of osteoporosis in patients hospitalized for hip fractures.

Predictive values of calcaneal quantitative ultrasound and dual energy X ray absorptiometry for non-vertebral fracture in older men: results from the MrOS study (Hong Kong).

The added value of trabecular bone score to FRAX® to predict major osteoporotic fractures for clinical use in Chinese older people: the Mr. OS and Ms. OS cohort study in Hong Kong