Hasil untuk "math.OC"

Valentina Capo, Sara Penna, Ludovica Santi et al.

Affette M. McCaw‐Binns, Jasneth A. Mullings, Yvette Holder

AbstractObjectiveTo identify why vital registration under‐reports maternal deaths in Jamaica.MethodsA cross‐sectional study was undertaken to identify all maternal deaths (during pregnancy or ≤ 42 days after pregnancy ended) occurring in 2008. Data sources included vital registration, hospital records, forensic pathology records, and an independent maternal mortality surveillance system. Potential cases were cross‐referenced to registered live births and stillbirths, and hospital records to confirm pregnancy status, when the pregnancy ended, and registration. Medical certificates were inspected for certification, transcription, and coding errors. Maternal mortality ratios (MMRs) for registered and/or unregistered deaths were calculated.ResultsOf 50 maternal deaths identified, 10 (20%) were unregistered. Eight unregistered deaths were coroners’ cases. Among 40 registered deaths, pregnancy was undocumented in 4 (10%). Among the other 36, 24 (67%) had been misclassified (59% direct and 89% indirect deaths). Therefore, only 12 (30%) registered maternal deaths had been coded as maternal deaths, yielding an MMR of 28.3 per 100 000 live births (95% confidence interval [CI] 12.3–48.3), which was 76% lower than the actual MMR of 117.8 (95% CI 85.2–150.4).ConclusionUnder‐reporting of maternal deaths in Jamaica in 2008 was attributable to delayed registration of coroners’ cases and misclassification. Timely registration of coroners’ cases and training of nosologists to recognize and code maternal deaths is needed.

B. Farsak, M. Oc, B. Oc et al.

Agustín Ciapponi, Amin Sharifan

Oguzhan Arun, Bahar Oc, Serkan Yildirim et al.

C Hawkey

Johan Richter, Maria Johansson, Teun J. de Vries et al.

Abstract Infantile malignant osteopeterosis (IMO) is a progressive, rare autosomal recessive disorder affecting osteoclast function. 50% of the affected children have a mutation in the Tcirg1 gene coding for one subunit of an osteoclast specific proton pump, OC116. The non-resorbed dense, sclerotic bones cause symptoms including pancytopenia and progressive visual loss and ultimately death. So far, the only curative treatment is hematopoietic stem cell (HSC) transplantation. The oc/oc mouse has a mutation in the gene homologous to Tcirg1 giving rise to similar symptoms as in patients leading to death of the mice at the age of 3–4 weeks. We have previously shown that the oc/oc mouse can be successfully treated with neonatal transplantation of normal HSC leading to prolonged survival and reversal of osteopetrosis (M. Johansson et al., Exp. Hematology34;242, 2006). In the current study we set out to develop HSC directed gene therapy for osteopetrosis in the oc/oc mouse model. As the bone marrow compartment is severely reduced in the oc/oc mouse fetal liver (FL) cells depleted of Ter119+ erythroid cells were used as a source of hematopoietic stem cells. We first established that wild type Ter119 depleted FL cells marked with a GFP vector and transplanted to newborn oc/oc mice i.p. could correct the osteopetrotic phenotype just as was shown for fresh bone marrow cells previously. Subsequently, Ter119 depleted FL cells from oc/oc mice were transduced with a retroviral vector expressing OC116 and GFP. In vitro transduction efficiency was 60–85%. One-day-old oc/oc mice were irradiated (400cGy) and transplanted i.p. with the transduced FL cells (1–3.5x106). 7 out of 14 mice survived past the expected lifespan and had 8–53% GFP+ cells in the peripheral blood at 3, 6 and 12 weeks. Analysis of bone structure with X-ray and histopathology showed an improvement at 8 weeks and an almost normal structure at 18 weeks, indicating induction of osteoclast activity. In vitro culture of osteoclasts from bone marrow from transplanted animals on bovine bone slices showed GFP marked osteoclasts and bone resorption, albeit at lower levels than for wild type cells. In the oc/oc mouse there is a block in B-lymphopoiesis leading to a reduced number of B-lymphocytes in the peripheral blood. In treated mice a reversal of this deficiency was observed. In summary we have demonstrated that the osteoclast defect seen in oc/oc mice can be successfully corrected by neonatal transplantation of gene modified hematopoietic stem cells and that this can lead to long-term survival of treated mice. This represents a significant step towards the development of gene therapy for osteopetrosis.