bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of the newborn screening programme for sickle cell disease in England: results for 2003-2005
Authors: Streetly Allison , Clarke Mary , Downing Melanie , Farrar Lisa , Foo Ying , Hall Kate , Kemp Helena , Newbold Jane , Walsh Paul , Yates Jenny , Henthorn Joan 
Published: April 2008

Objectives This paper reports early screening results from the newborn sickle cell disease screening programme recently implemented in England. Setting England. Screening is offered at 5-8 days of age as part of the existing bloodspot test and offered to all babies irrespective of ethnicity. Methods The laboratory methods recommended are high performance liquid chromatography (HPLC) and iso-electric focusing (IEF). 15 Two methods of analysis must be applied to all screen positive results. The conditions screened for are:- Sickle cell anaemia (Hb SS), Hb SC disease, Hb S/β-thalassaemia, Hb S/DPunjab, Hb S/OArab, Hb S/HPFH. Carriers identified for the common haemoglobin variants are reported to parents and follow-up counselling is offered. A bespoke laboratory quality assurance programme has been established which has defined standards of satifactory performance. Results Provisional figures from the first seven months of screening (up to March 2004) 108,255 infants were screened gave a screen positive rate of 1:900 for these high prevalence areas and a carrier rate of 2.7%. Figures for 2004-2005 show about 250 significant screen positive results for sickle cell disorders and about 6,500 carriers were identified. The birth prevalence for screen positive results from 2004-05 is 1:1500. We estimate that when there is countrywide data, the national birth prevalence will be about 1:2000-1:2,500. Conclusion The results from the national newborn sickle cell screening programme in England - show that the sickle cell disorders are as common as cystic fibrosis (CF) in England, although the distribution of cases is concentrated in London and other urban areas. The findings and approach to implementation adopted in England may be of interest to other Western European countries with increasing rates of sickle cell disease who are considering such programmes and also to other developed countries.
The effect of an organized, nationwide breast cancer screening programme on non-organized mammography activities
Authors: Boncz Imre , Sebestyén Andor , Pintér Istvén , Battyéany Istvéan , Ember Istvéan 
Published: April 2008

Objectives To analyse the effect of an organized, nationwide breast cancer screening programme on non-organized mammography activities in Hungary. Setting The nationwide dataset of the Hungarian National Health Insurance Fund Administration covering the years 2000-2005. Methods Data derived from the nationwide database of the Hungarian National Health Insurance Fund Administration. The study includes all women undergoing mammography before (2000-2001) and after (2002-2003/2004-2005) the introduction of organized screening. Results The number of women having non-organized (opportunistic/diagnostic) mammograms was around 250,000 in 2000-2001, but increased to 350,000 in 2005. In the age group 45-64 years in 2000-2001, only 27.4% of all women undergoing mammography were examined within locally-organized programmes. After the introduction of the nationwide programme, this percentage increased to 61.0% in 2002-2003, and 56.3% in 2004-2005. After the introduction of the nationwide organized programme (2002-2003), the proportion of organized screening mammographics remained among the highest in county Hajdú-Bihar (78.4%) and Zala (88.3%) and increased significantly in county Vas (87.7%). Conclusion The introduction of an organized nationwide screening programme in Hungary resulted in increases in the number of screening mammographics, and also of non-organized mammographics. Although the ratio of organized screening versus non-organized mammography changed in favour of screening mammographics, there are large within-country differences between counties.
Estimating the cumulative risk of a false-positive under a regimen involving various types of cancer screening tests
Authors: Baker Stuart G , Kramer Barnett S 
Published: April 2008

Introduction Objectives When evaluating screening for the early detection of cancer, it is important to estimate both harms and benefits. One common harm is a false-positive (FP), which is a positive screening result, perhaps followed by an invasive test, with no cancer detected on the diagnostic work-up or within a specified time period. An important goal is to estimate the risk of at least one FP, which we call the cumulative risk of an FP, if persons took a regimen of various screening tests, as is commonly recommended. The estimation is complicated because the data come from a study in which subjects are offered various screening tests in rounds with some missing tests in most subjects. Previous methods for estimating cumulative risk of FPs with a single type of test are not directly applicable, so a new approach was developed. Methods The tests were ordered by appearance, where the last test was either the first FP (analogous to a failure time) or the last test taken with no FPs having occurred on that test or previously (analogous to a censoring time). We applied a Kaplan-Meier approach for survival analysis with the innovation that the hazard for a first FP for a given test depends on the type of test and number of previous tests of that type which were taken. Results The method is illustrated with data from the screening arm of the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. With an FP defined as a diagnostic work-up in the absence of cancer (or advanced adenoma) within three years, the probability of at least one FP among 14 tests in men was 60.5% with 95% confidence interval of (59.3%, 61.6%). Conclusion A simple estimate is proposed for the probability of at least one FP if persons took a regimen of multiple screening tests of different types. The methodology is useful for summarizing the burden of multiphasic screening programmes.
The implementation of revised guidelines and the performance of a screening programme for congenital Hypothyroidism
Authors: Korada M , Kibirige M , Turner S , Day J , Johnstone H , Cheetham T 
Published: April 2008

Objectives To see whether revised screening standards and health-professional training are associated with changes in the performance of a neonatal screening programme for congenital hypothyroidism (CHT). Methods Screening data from the regional screening service in Durham and Newcastle, which covers north-east England and North Cumbria. Setting We assessed the timing of the different stages of the screening process leading up to the introduction of the revised guidelines between April 2004 and March 2005 (year 1) and afterwards between April 2005 and March 2006 (year 2) in all babies notified as having CHT. We also assessed the interval between sampling and specimen arrival in the laboratory at the beginning and end of year 2 in all babies screened. Results Twenty-three babies tested positive or borderline in year 1 and 18 babies in year 2. There was reduced variability in the overall time from birth to notification in year 2 versus year 1 ( P = 0.001). This reduction was a consequence of a reduced interval between sample collection and arrival in the laboratory ( P = 0.047) and for the laboratory to notify the positive test result ( P = 0.003). There was a reduction in the mean time from sampling to receipt by the laboratory in the 2997 babies screened in the final month compared with the 2498 babies screened in the first month of year 2 ( P = 0.01). Conclusion There was an improvement in neonatal screening programme performance around the time that revised neonatal screening guidelines were introduced. This highlights the importance of ongoing education and training for those involved in screening programmes.
Article Commentary: The English national screening programme for sight-threatening diabetic retinopathy
Authors: Scanlon P H 
Published: April 2008

Objectives The main objective of the national screening programme is to reduce the risk of sight loss among people with diabetes due to diabetic retinopathy (DR). Methods Offering two-field mydriatic digital photographic screening to all people with diabetes in England over the age of 12 years. Stage of development The programme is in its infancy, receiving the first year's annual reports from approximately 96 screening programmes, each of which have developed to offer screening to a minimum number of 12,000 people with diabetes, which would cover a population of 350,000 people with 3.4% diabetes prevalence. The national programme has commenced the External quality assurance (QA) programme in order to achieve and sustain the highest possible standards. Potential benefits England has a population of two million people with diabetes over the age of 12 and it is believed that there is a prevalence of blindness of 4200 and an annual incidence of blindness of 1280 people with diabetes. This programme has the potential to reduce the prevalence of blindness in England from 4200 people to 1000 people and a conservative estimate of reducing the annual incidence of DR blindness by one-third would save 427 people per annum from blindness. These figures are based on the UK certification of blindness but if World Health Organization (WHO) definitions are used the prevalence, incidence and potential reductions in blindness are much greater.
Vitamin D Receptor–Dependent 1α,25(OH)2 Vitamin D3–Induced Anti-Apoptotic PI3K/AKT Signaling in Osteoblasts
Authors: Zhang Xiaoyu , Zanello Laura P 
Published: April 2008

Abstract
Osteoblast apoptosis plays a crucial role in bone remodeling. Physiological doses of 1α,25(OH)2-vitamin D3 (1,25D) protect osteoblasts against apoptosis by means of mechanisms only partially understood. We studied activation of an Akt survival cascade downstream of 1,25D nongenomic stimulation of phosphatidylinositide-3′-kinase (PI3K) in osteoblastic cells. We measured a dose- and time-dependent 1,25D induction of Akt phosphorylation (p-Akt) in cultured osteoblastic cells. Maximal response was achieved with 10 nM 1,25D after 5 min. We found that staurosporine (STSP)-induced apoptosis was significantly reduced in 1,25D-pretreated osteoblasts. 1,25D prosurvival effects were abolished when cells were preincubated with inhibitors of PI3K activation. By means of siRNA silencing, we proved that 1,25D induction of p-Akt requires a classic vitamin D receptor (VDR) in osteoblasts. Furthermore, non-osteoblastic CV-1 cells transfected with an enhanced green fluorescent protein (EGFP)-VDR construct responded to 1,25D treatment with a rapid p-Akt response associated with increased cell survival not detected in native, nontransfected cells. We measured increased levels of p-Akt substrates p-Bad and p-FKHR and significantly reduced activity of caspases 8 and 3/7 after 1,25D treatment. In addition, 1,25D-induced protection against apoptosis was abolished when osteoblasts were preincubated with pertussis toxin. We conclude that anti-apoptotic effects of 1,25D in osteoblasts occur through nongenomic activation of a VDR/PI3K/Akt survival pathway that includes phosphorylation of multiple p-Akt substrates and reduction of caspase activities.
Randomized Controlled Trial of the Effects of Calcium With or Without Vitamin D on Bone Structure and Bone-Related Chemistry in Elderly Women With Vitamin D Insufficiency
Authors: Zhu Kun , Bruce David , Austin Nicole , Devine Amanda , Ebeling Peter R , Prince Richard L 
Published: April 2008

Abstract
There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status. The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency. Three hundred two elderly women (age, 77.2 ± 4.6 yr) with serum 25(OH)D concentrations &lt;60 nM participated in a 1-yr randomized, double-blind, placebo-controlled trial. All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol (vitamin D2) or identical placebo (control). The effects of time and time treatment interactions were evaluated by repeated-measures ANOVA. At baseline, calcium intake was 1100 mg/d, and 25(OH)D was 44.3 ± 12.9 nM; this increased in the vitamin D group by 34% but not the control group after 1 year (59.8 ± 13.8 versus 45.0 ± 13.3 nM, p &lt; 0.001). Total hip and total body BMD increased significantly, and procollagen type I intact N-terminal propeptide (PINP) decreased during the study with no difference between the treatment groups (hip BMD change: vitamin D, +0.5%; control, +0.2%; total body BMD change: vitamin D, +0.4%; control, +0.4%; PINP change: vitamin D, −3.9%; placebo, −2.8%). Although the fasting plasma and urine calcium increased in both groups equally, there was no detectable change in serum PTH. The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption, which fell equally in both groups (vitamin D, −17.4%; control, −14.8%). In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency, vitamin D2 1000 IU for 1 year has no extra beneficial effect on bone structure, bone formation markers, or intestinal calcium absorption over an additional 1000 mg of calcium. Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency.
Low Serum 25-Hydroxyvitamin D Levels Associated With Falls Among Japanese Community-Dwelling Elderly
Authors: Suzuki Takao , Kwon Jinhee , Kim Hunkyung , Shimada Hiroyuki , Yoshida Yuko , Iwasa Hajime , Yoshida Hideyo 
Published: April 2008

Abstract
Previous studies have shown that low serum 25-hydroxyvitamin D [25(OH)D] level is a risk factor for falls among the elderly in European and North American populations. We used a cross-sectional community-based survey to study the association of serum 25(OH)D level and falls among Japanese community-dwelling elderly. A total of 2957 elderly persons (950 men and 2007 women) 65–92 yr of age who participated in mass health examinations for the prevention of geriatric syndrome for the elderly underwent an interview, blood analysis, and physical performance testing. Experience of falls over the previous year was assessed in an interview. Physical performance tests of handgrip strength, stork standing time with the eyes open, and normal waking speed as risk factors for falls among the elderly were conducted. Serum albumin and 25(OH)D concentrations were analyzed. Mean 25(OH)D concentration was significantly lower in women than in men (p &lt; 0.001). Women showed a significant decline of 25(OH)D level with increased age (p &lt; 0.001). There was also a significant difference in the prevalence of 25(OH)D insufficiency [25(OH)D level &lt; 20 ng/ml] between the sexes (p &lt; 0.001). The rate of falls was significantly higher in the lowest quartile of 25(OH)D level in women (p = 0.02) and in women with 25(OH)D insufficiency (p = 0.001). Women also showed significant declines in all three fall-related physical performance tests. Multiple logistic regression analysis showed significant and independent associations between 25(OH)D level and experience of falls in women only (p = 0.01). Low 25(OH)D level was significantly associated with a high prevalence of falls in Japanese elderly women because of their inferior physical performance. Low serum 25(OH)D levels appear preventable and easily treated; there is an evident need for greater awareness to screen and thus prevent this condition.
Linkage Screen for BMD Phenotypes in Male and Female COP and DA Rat Strains
Authors: Koller Daniel L , Liu Lixiang , Alam Imranul , Sun Qiwei , Econs Michael J , Foroud Tatiana , Turner Charles H 
Published: April 2008

Abstract
Because particular inbred strains of experimental animals are informative for only a subset of the genes underlying variability in BMD, we undertook a genome screen to identify quantitative trait loci (QTLs) in 828 F2 progeny (405 males and 423 females) derived from the Copenhagen 2331 (COP) and dark agouti (DA) strains of rats. This screen was performed to complement our study in female Fischer 344 (F344) and Lewis (LEW) rats and to further delineate the factors underlying the complex genetic architecture of BMD in the rat model. Microsatellite genotyping was performed using markers at an average density of 20 cM. BMD was measured by pQCT and DXA. These data were analyzed in the R/qtl software to detect QTLs acting in both sexes as well as those having sex-specific effects. A QTL was detected in both sexes on chromosome 18 for midfemur volumetric BMD (vBMD; genome-wide, p &lt; 0.01). On distal chromosome 1, a QTL was found for femur and vertebral aBMD as well as distal femur vBMD, and this QTL appears distinct from the proximal chromosome 1 QTL impacting BMD in our F344/LEW cross. Additional aBMD and vBMD QTLs and several sex-specific QTLs were also detected. These included a male-specific QTL (p &lt; 0.01) on chromosome 8 and a female-specific QTL on chromosomes 7 and 14 (p &lt; 0.01). Few of the QTLs identified showed overlap with the significant QTLs from the F344/LEW cross. These results confirm that the genetic influence on BMD in the rat model is quite complex and would seem to be influenced by a number of different genes, some of which have sex-specific effects.
BMD and Bone Geometry in Transtibial and Transfemoral Amputees
Authors: Sherk Vanessa D , Bemben Michael G , Bemben Debra A 
Published: April 2008

Abstract
Prolonged unloading of bone(s) in the residual limb after amputation may cause significant bone loss in the hip and distal bony end of the residual limb. The purpose of this study was to examine the effect of amputation on bone geometry, volumetric BMD (vBMD), and areal BMD (aBMD) by comparing the intact and residual limbs in unilateral transfemoral and transtibial amputees. Amputees (seven above-knee; seven below-knee) and two groups of nonamputee control subjects gave informed consent to participate in this study. aBMD of the dual proximal femur, lumbar spine, and total body was assessed using DXA. Bone geometry and vBMD were assessed at the distal ends of the residual limb and intact limb and at a comparable cross-sectional slice of the intact limb using pQCT (Stratec XCT 3000). There were no significant group differences in age, height, weight, physical activity, time as an amputee, hours wearing a prosthesis per day, or total body and lumbar spine BMD and BMC. There were significant side × group interactions for total hip, femoral neck, and trochanter BMD, with the amputated side having lower BMD, and differences being most severe in above-knee amputees. Total and cortical vBMD and area were significantly lower at the end of the residual limb compared with the similar slice of the intact limb for both above- and below-knee amputees. In conclusion, amputees exhibited large decrements in BMD, both at the hip and at the end of the residual limb, compared with the intact side. These lower BMD values put amputees, particularly the above-knee amputees, at increased risk for osteoporosis and fragility fractures in the hip.
Expression and Regulation of the Vitamin D Receptor in the Zebrafish, Danio rerio
Authors: Craig Theodore A , Sommer Stacy , Sussman Caroline R , Grande Joseph P , Kumar Rajiv 
Published: April 2008

Abstract
Vitamin D and vitamin D metabolites such as 25-hydroxyvitamin D and 1α,25-dihydroxyvitamin D [1α,25(OH)2D3] circulate in the serum of fish. The receptor for 1α,25(OH)2D3 (VDR) has previously been cloned from fish intestine, and ligand binding assays have shown the presence of the VDR in the gills, intestine, and liver of fish. Using immunohistochemical methods with specific antibodies against the VDR, we now report that the VDR is widely expressed in tissues of the adult male and female zebrafish, Danio rerio, specifically in epithelial cells of gills, tubular cells of the kidney, and absorptive cells in the intestine. Additionally, the VDR is expressed in the skin, the olfactory organ, the retina, brain, and spinal cord. Sertoli cells of the testis, oocytes, acinar cells of the pancreas, hepatocytes, and bile duct epithelial cells express substantial amounts of the receptor. Osteoblast-like cells and chondrocytes also express VDR. Preimmune serum and antiserum preadsorbed with Danio VDR protein fails to detect VDR in the same tissues. The VDR is also present in the developing eye, brain, and otic vesicle of 48- and 96-h postfertilization zebrafish embryos. Parenteral administration of 1α,25(OH)2D3 increases concentrations of VDR in intestinal epithelial cells but not in epithelial cells of the gills. Lithocholic acid, however, does not alter concentrations of VDR after parenteral administration. The data suggest that VDR is widely distributed in tissues of the zebrafish, D. rerio, and is likely to play important roles in epithelial transport, bone, and endocrine function. Furthermore, concentrations of the receptor seem to be regulated by its ligand, 1α,25-dihydroxyvitamin D but not by lithocholic acid. Zebrafish may serve as a useful model in which to assess the function of the VDR in diverse tissues.
Relationship of Blood Lead Levels to Incident Nonspine Fractures and Falls in Older Women: The Study of Osteoporotic Fractures
Authors: Khalil Naila , Cauley Jane A , Wilson John W , Talbott Evelyn O , Morrow Lisa , Hochberg Marc C , Hillier Teresa A , Muldoon Susan B , Cummings Steven R 
Published: April 2008

Abstract
Lead is stored in the skeleton and can serve as an endogenous source for many years. Lead may influence the risk of fracture, through direct effects on bone strength or indirectly by disturbing neuromuscular function and increasing the risk of falls. The objective of this analysis is to test the hypothesis that women with higher blood lead levels experience higher rates of falls and fracture. This was a prospective cohort study of 533 women 65–87 yr of age enrolled in the Study of Osteoporotic Fractures at two U.S. research centers (Baltimore, MD; Monongahela Valley, PA) from 1986 to 1988. Blood lead levels (in μg/dl) were measured in 1990–1991 by atomic absorption spectrophotometry and classified as “low” (≤3; lower 15th percentile, referent); “medium” (4–7); or “high” (≥8; upper 15th percentile). Total hip BMD was measured by DXA twice, 3.55 yr apart. Information on falls was collected every 4 mo for 4 yr. Incident nonspine fractures were identified and confirmed over 10 yr. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of fracture. Generalized estimating equations were used to calculate the incident rate ratio of falls (95% CI). The mean blood lead level was 5.3 ± 2.3 (SD) μg/dl (range, 1–21 μg/dl). Baseline BMD was 7% lower in total hip and 5% lower in femoral neck in the highest compared with lowest blood lead group (p &lt; 0.02). Hip bone loss tended to be greater in the high lead group, but differences were not significant. In multivariable adjusted models, women with high blood lead levels had an increased risk of nonspine fracture (HR = 2.50; 95% CI = 1.25, 5.03; p trend = 0.016) and higher risk of falls (incident rate ratio = 1.62; 95% CI = 1.07, 2.45; p trend = 0.014) compared with women with lowest lead level. Blood lead levels are associated with an increased risk of falls and fractures, extending the negative health consequences of lead to include osteoporotic fractures.