Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate

Patterns in random walks and Brownian motion

We ask if it is possible to find some particular continuous paths of unit length in linear Brownian motion. Beginning with a discrete version of the problem, we derive the asymptotics of the expected waiting time for several interesting patterns. These suggest corresponding results on the existence/non-existence of continuous paths embedded in Brownian motion. With further effort we are able to prove some of these existence and non-existence results by various stochastic analysis arguments. A list of open problems is presented.Comment: 31 pages, 4 figures. This paper is published at http://link.springer.com/chapter/10.1007/978-3-319-18585-9_

Intravenous or oral iron for treating iron deficiency anaemia during pregnancy: systematic review and meta-analysis

OBJECTIVES:To compare the effects on perinatal maternal and neonatal outcomes of intravenous and oral iron therapy as first-line treatment of iron deficiency anaemia (IDA) in pregnant women. STUDY DESIGN:A meta-analysis, applying fixed and random effects models, of randomised controlled trials (RCTs) that compared the effects of intravenous and oral iron therapy for pregnant women with IDA. DATA SOURCES:MEDLINE, EMBASE, Scopus, Cochrane Register of Controlled Trials, Web of Science; bibliographies of identified articles. DATA SYNTHESIS:Fifteen eligible studies with a total of 1938 participants were identified. Each was at high risk of bias in at least one domain; ten were undertaken in low or middle income countries. Evidence (from nine RCTs) that intravenous iron was superior to oral iron in reducing the need for blood transfusion at delivery was low quality (Peto odds ratio, 0.19 [95% CI, 0.05-0.78]; number needed to treat, 95 [95% CI, 81-348]). Evidence that intravenous iron was superior to oral iron in increasing neonatal birthweight (eight RCTs: mean difference, 58 g; 95% CI, 4-112 g) or reducing the rate of breastfeeding cessation within 24 months of delivery (one RCT: hazard ratio, 0.70; 95% CI, 0.50-0.99) was of low or very low quality. While intravenous iron treatment was superior to oral iron for improving maternal haematological parameters at delivery, their effects on neonatal haematological parameters were similar. CONCLUSIONS:There is no strong evidence that first-line therapy with intravenous iron is superior to oral administration for treating IDA in pregnant women. The few identified differences in outcomes were small in magnitude and from studies at high risk of bias. REGISTRATION:International Prospective Register of Systematic Reviews (PROSPERO), CRD42019120652.Alaa Qassim, Rosalie M Grivell, Amanda Henry, Giselle Kidson‐Gerber, Antonia Shand, Luke E Grzeskowia

Rapid increase in intravenous iron therapy for women of reproductive age in Australia

Abstract not available.Antonia W Shand, Jane Bell, Amanda Henry, Luke E Grzeskowiak, Giselle Kidson-Gerber, Sallie Pearson, Natasha Nassa

Entrepreneurial autonomy and its dynamics

Founding and owning an independent business does not automatically provide the owner/founder with autonomy. Autonomy-motivated entrepreneurs must often make an effort to achieve and maintain autonomy. The aim of this research is to investigate the experience of autonomy, its variations over time, and how it is affected by a range of internal and external conditions as well as the actions of the entrepreneur. The research design utilises a qualitative methodology, asking 61 business owner/founders to respond to a range of vignettes that depict autonomy-related tensions. The results indicate that whether a business owner actively experiences autonomy is best assessed by not only asking for the degree of decisional freedom he or she currently enjoys, but also whether that degree of freedom is chosen voluntarily. Other main findings are that customers regularly represent challenges to autonomy, whereas business partners are often seen to enhance it. The results reveal various autonomy dynamics, showing movements between currently exercised, temporarily sacrificed, and involuntarily lost decisional freedoms. These movements are influenced by a range of factors, including the importance of particular customers or assignments, the phase in the business life cycle, and the financial performance of the business