Mesenchymal stem cells with increased stromal cell-derived factor 1 expression enhanced fracture healing

Treatment of critical size bone defects pose a challenge in orthopedics. Stem cell therapy together with cytokines has the potential to improve bone repair as they cause the migration and homing of stem cells to the defect site. However, the engraftment, participation, and recruitment of other cells within the regenerating tissue are important. To enhance stem cell involvement, this study investigated overexpression of stem cells with stromal cell-derived factor 1 (SDF-1) using an adenovirus. We hypothesized that these engineered cells would effectively increase the migration of native cells to the site of fracture, enhancing bone repair. Before implantation, we showed that SDF-1 secreted by transfected cells increased the migration of nontransfected cells. In a rat defect bone model, bone marrow mesenchymal stem cells overexpressing SDF-1 showed significantly (p=0.003) more new bone formation within the gap and less bone mineral loss at the area adjacent to the defect site during the early bone healing stage. In conclusion, SDF-1 was shown to play an important role in accelerating fracture repair and contributing to bone repair in rat models, by recruiting more host stem cells to the defect site and encouraging osteogenic differentiation and production of bone

Effects of Soil Conservation Practices on Sediment Yield from Forest Road Ditches in Northern Iran

The fine-textured soil in forest road ditches is very susceptible to water erosion especially in rainy seasons in Hyrcanian forest. This study examined the yield of ditch segment-scale sediment after releasing two flow rates of 5 l s-1 and 10 l s-1 in segments treated by riprap (RR), grass cover by Festuca arundinacea L. (GC), compacted cotton geotextile (CG) and wooden wattle by local slash (WW). Sediment sampling from the runoff was carried out at the end of each segment every minute. Runoff flow velocity in different treatments was measured using an electromagnetic flow meter. Sediment concentration and runoff velocity in treatments of RR, GC, CG, WW was significantly lower than that of the control plot (Ctl). Increasing flow rate from 5 l s-1 to 10 l s-1 caused no significant change in sediment concentration (except for Ctl and RR) and runoff velocity (except for Ctl and CG), which means that some water might have penetrated into treated soil by RR, GC and WW and this is not acceptable in forest road maintenance practices. Sediment yield from RR (0.36 g l-1) and Ctl (0.50 g l-1) under the flow rate of 10 l s-1 was significantly higher than that of 5 l s-1 with values of 0.21 g l-1 and 0.38 g l-1, respectively. Minimum amount of sediment concentration was observed for CG (0.20 g l-1) with compacted ditch bed. Moreover, runoff velocity in CG and Ctl under the flow rate of 10 l s-1 was significantly higher than that of 5 l s-1. For a forest road with dimension 30×50 cm, slope of 5%, and clay soil with porosity of 57%, treatments of compacted CG can be used in ditch with low flow rates (5 l s-1) and high flow rate (10 l s-1) because of their high efficiency in reducing sediment yield

Linkage of maternity hospital episode statistics birth records to birth registration and notification records for births in England 2005–2006: quality assurance of linkage

Objectives The objectives of this study were to describe the methods used to assess the quality of linkage between records of babies’ birth registration and hospital birth records, and to evaluate the potential bias that may be introduced because of these methods. Design/setting Data from the civil registration and the notification of births previously linked by the Office for National Statistics (ONS) had been further linked to birth records from the Hospital Episode Statistics (HES) for babies born in England. We developed a deterministic, six-stage algorithm to assess the quality of this linkage. Participants All 1 170 790 live, singleton births, occurring in National Health Service hospitals in England between 1 January 2005 and 31 December 2006. Primary outcome measure The primary outcome was the number of successful links between ONS birth records and HES birth records. Rates of successful linkage were calculated for the cohort and the characteristics associated with unsuccessful linkage were identified. Results Approximately 92% (1 074 572) of the birth registration records were successfully linked with a HES birth record. Data quality and completeness were somewhat poorer in HES birth records compared with linked birth registration and birth notification records. The quality assurance algorithms identified 1456 incorrect linkages (<1%). Compared with the linked dataset, birth records were more likely to be unlinked if babies were of white ethnic origin; born to unmarried mothers; born in East England, London, North West England or the West Midlands; or born in March. Conclusions It is possible to link administrative datasets to create large cohorts, allowing researchers to explore important questions about exposures and childhood outcomes. Missing data, coding errors and inconsistencies mean it is important that the quality of linkage is assessed prior to analysis

Fast plasma sintering delivers functional graded materials components with macroporous structures and osseointegration properties

We explored the osseointegration potential of two macroporous titanium surfaces obtained using fast plasma sintering (FPS): Ti macroporous structures with 400-600 µmØ pores (TiMac400) and 850-1000 µmØ pores (TiMac850). They were compared against two surfaces currently in clinical use: Ti-Growth® and air plasma spray (Ti-Y367). Each surface was tested, once placed over a Ti-alloy and once onto a CoCr bulk substrate. Implants were placed in medial femoral condyles in 24 sheep. Samples were explanted at four and eight weeks after surgery. Push-out loads were measured using a material-testing system. Bone contact and ingrowth were assessed by histomorphometry and SEM and EDX analyses. Histology showed early osseointegration for all the surfaces tested. At 8 weeks, TiMac400, TiMac850 and Ti-Growth® showed deep bone ingrowth and extended colonisation with newly formed bone. The mechanical push-out force was equal in all tested surfaces. Plasma spray surfaces showed greater bone-implant contact and higher level of pores colonisation with new bone than FPS produced surfaces. However, the void pore area in FPS specimens was significantly higher, yet the FPS porous surfaces allowed a deeper osseointegration of bone to implant. FPS manufactured specimens showed similar osseointegration potential to the plasma spray surfaces for orthopaedic implants. FPS is a useful technology for manufacturing macroporous titanium surfaces. Furthermore, its capability to combine two implantable materials, using bulk CoCr with macroporous titanium surfaces, could be of interest as it enables designers to conceive and manufacture innovative components. FPS delivers functional graded materials components with macroporous structures optimised for osseointegration

Challenges and opportunities for ELSI early career researchers

Background: Over the past 25 years, there has been growing recognition of the importance of studying the Ethical, Legal and Social Implications (ELSI) of genetic and genomic research. A large investment into ELSI research from the National Institutes of Health (NIH) Human Genomic Project budget in 1990 stimulated the growth of this emerging field; ELSI research has continued to develop and is starting to emerge as a field in its own right. The evolving subject matter of ELSI research continues to raise new research questions as well as prompt re-evaluation of earlier work and a growing number of scholars working in this area now identify themselves as ELSI scholars rather than with a particular discipline. Main text: Due to the international and interdisciplinary nature of ELSI research, scholars can often find themselves isolated from disciplinary or regionally situated support structures. We conducted a workshop with Early Career Researchers (ECRs) in Oxford, UK, and this paper discusses some of the particular challenges that were highlighted. While ELSI ECRs may face many of the universal challenges faced by ECRs, we argue that a number of challenges are either unique or exacerbated in the case of ELSI ECRs and discuss some of the reasons as to why this may be the case. We identify some of the most pressing issues for ELSI ECRs as: interdisciplinary angst and expertise, isolation from traditional support structures, limited resources and funding opportunities, and uncertainty regarding how research contributions will be measured. We discuss the potential opportunity to use web 2.0 technologies to transform academic support structures and address some of the challenges faced by ELSI ECRs, by helping to facilitate mentoring and support, access to resources and new accreditation metrics. Conclusion: As our field develops it is crucial for the ELSI community to continue looking forward to identify how emerging digital solutions can be used to facilitate the international and interdisciplinary research we perform, and to offer support for those embarking on, progressing through, and transitioning into an ELSI research career

Associations between gestational age at birth and infection-related hospital admission rates during childhood in England: Population-based record linkage study

BACKGROUND: Children born preterm (<37 completed weeks' gestation) have a higher risk of infection-related morbidity than those born at term. However, few large, population-based studies have investigated the risk of infection in childhood across the full spectrum of gestational age. The objectives of this study were to explore the association between gestational age at birth and infection-related hospital admissions up to the age of 10 years, how infection-related hospital admission rates change throughout childhood, and whether being born small for gestational age (SGA) modifies this relationship. METHODS AND FINDINGS: Using a population-based, record-linkage cohort study design, birth registrations, birth notifications and hospital admissions were linked using a deterministic algorithm. The study population included all live, singleton births occurring in NHS hospitals in England from January 2005 to December 2006 (n = 1,018,136). The primary outcome was all infection-related inpatient hospital admissions from birth to 10 years of age, death or study end (March 2015). The secondary outcome was the type of infection-related hospital admission, grouped into broad categories. Generalised estimating equations were used to estimate adjusted rate ratios (aRRs) with 95% confidence intervals (CIs) for each gestational age category (<28, 28-29, 30-31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42 weeks) and the models were repeated by age at admission (<1, 1-2, 3-4, 5-6, and 7-10 years). An interaction term was included in the model to test whether SGA status modified the relationship between gestational age and infection-related hospital admissions. Gestational age was strongly associated with rates of infection-related hospital admissions throughout childhood. Whilst the relationship attenuated over time, at 7-10 years of age those born before 40 weeks gestation were still significantly higher in comparison to those born at 40 weeks. Children born <28 weeks had an aRR of 6.53 (5.91-7.22) during infancy, declining to 3.16 (2.50-3.99) at ages 7-10 years, in comparison to those born at 40 weeks; whilst in children born at 38 weeks, the aRRs were 1·24 (1.21-1.27) and 1·18 (1.13-1.23), during infancy and aged 7-10 years, respectively. SGA status modified the effect of gestational age (interaction P<0.0001), with the highest rate among the children born at <28 weeks and SGA. Finally, study findings indicated that the associations with gestational age varied by subgroup of infection. Whilst upper respiratory tract infections were the most common type of infection experienced by children in this cohort, lower respiratory tract infections (LRTIs) (<28 weeks, aRR = 10.61(9.55-11.79)) and invasive bacterial infections (<28 weeks, aRR = 6.02 (4.56-7.95)) were the most strongly associated with gestational age at birth. Of LRTIs experienced, bronchiolitis (<28 weeks, aRR = 11.86 (10.20-13.80)), and pneumonia (<28 weeks, aRR = 9.49 (7.95-11.32)) were the most common causes. CONCLUSIONS: Gestational age at birth was strongly associated with rates of infection-related hospital admissions during childhood and even children born a few weeks early remained at higher risk at 7-10 years of age. There was variation between clinical subgroups in the strength of relationships with gestational age. Effective infection prevention strategies should include focus on reducing the number and severity of LRTIs during early childhood

Gestational age and hospital admissions during childhood, the TIGAR study: population-based, record linkage study in England

Objectives: To explore the association between gestation at birth and hospital admissions to age 10 years and how admission rates change throughout childhood. Design: We used a population-based record-linkage cohort study design. Birth registration, birth notification and Hospital Episode Statistics were linked using a deterministic algorithm. Setting: National Health Service (NHS) hospitals in England, UK Participants: All live, singleton births in NHS hospitals occurring in England January 2005 to December 2006 (n=1,018,136). Main outcome measures: The primary outcome was all inpatient hospital admissions from birth to age 10 years, death or study end (March 2015) and the secondary outcome was the main cause of admission, which was defined as the first International Classification of Disease-10 (ICD10) code within each hospital admission record. Results: 525,039 (52%) children experienced at least one hospital admission during the study period. Hospital admissions during childhood were strongly associated with gestational age at birth (<28, 28-29, 30-31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, and 42 weeks). Compared to children born full term (40 weeks’ gestation), those born extremely preterm (<28 weeks) had the highest rate of hospital admission throughout childhood (adjusted RR, aRR=4·29, 95%CI: 4·58 to 5·30). Even children born at 38 weeks had a higher rate of hospital admission throughout childhood (aRR=1·19, 95%CI: 1·16 to 1·22). However, the association between gestational age and hospital admission decreased with increasing age (interaction p<0·001). Children born <28 weeks had an aRR of 6·38 (95%CI: 5.80 to 6.85) during infancy, declining to 3·28 (95%CI: 2.82 to 3.82) at ages 7-10, in comparison to those born full term; whilst in children born at 38 weeks, the aRRs were 1·29 (95%CI: 1.27 to 1.31) and 1·16 (95%CI: 1.13 to 1.19), during infancy and ages 7-10 respectively. Infection was the main cause of excess hospital admissions at all ages, but particularly during infancy. Respiratory and gastrointestinal conditions also accounted for a large proportion of admissions during the first two years of life. Conclusions: Whilst the association between gestational age and hospital admission rates decreased with age, an excess risk remained throughout childhood, even among children born at 38 and 39 weeks of gestation. Strategies aimed at the prevention and management of childhood infections should target children born preterm and those born a few weeks early