Collaborative genetic mapping of 12 forensic short tandem repeat (STR) loci on the human X chromosome

A large number of short tandem repeat (STR) markers spanning the entire human X chromosome have been described and established for use in forensic genetic testing. Due to their particular mode of inheritance, X-STRs often allow easy and informative haplotyping in kinship analyses. Moreover, some X-STRs are known to be tightly linked so that, in combination, they constitute even more complex genetic markers than each STR taken individually. As a consequence, X-STRs have proven particularly powerful in solving complex cases of disputed blood relatedness. However, valid quantification of the evidence provided by X-STR genotypes in the form of likelihood ratios requires that the recombination rates between markers are exactly known. In a collaborative family study, we used X-STR genotype data from 401 two- and three-generation families to derive valid estimates of the recombination rates between 12 forensic markers widely used in forensic testing, namely DXS10148, DXS10135, DXS8378 (together constituting linkage group I), DXS7132, DXS10079, DXS10074 (linkage group II), DXS10103, HPRTB, DXS10101 (linkage group III), DXS10146, DXS10134 and DXS7423 (linkage group IV). Our study is the first to simultaneously allow for mutation and recombination in the underlying likelihood calculations, thereby obviating the bias-prone practice of excluding ambiguous transmission events from further consideration. The statistical analysis confirms that linkage groups I and II are transmitted independently from one another whereas linkage groups II, III and IV are characterised by inter-group recombination fractions that are notably smaller than 50%. Evidence was also found for recombination within all four linkage groups, with recombination fraction estimates ranging as high as 2% in the case of DXS10146 and DXS10134.     

Characteristics of Perforated Appendicitis: Effect of Delay Is Confounded by Age and Gender

Introduction  

The effect of age and gender on time to perforation in acute appendicitis has not been well characterized. This study examined the relationship between duration of disease and appendiceal perforation in different subgroups of age and gender.     

<Emphasis Type="Italic">Hunter disease eClinic:</Emphasis>interactive,computer-assisted,problem-based approach to independent learning about a rare genetic disease

Background  

Computer-based teaching (CBT) is a well-known educational device, but it has never been applied systematically to the teaching of a complex, rare, genetic disease, such as Hunter disease (MPS II).     

Protocol of GLUcose COntrol Safety and Efficacy in type 2 DIabetes,a NETwork meta‐analysis: GLUCOSE DINET protocol—Rational and design

The aim of this study was to propose a ranking of the currently available antidiabetic drugs, regarding vascular clinical outcomes, in patients with type 2 diabetes, through a network meta‐analysis approach. Randomized clinical trials, regardless of the blinding design, testing contemporary antidiabetic drugs, and considering clinically relevant outcomes in patients with type 2 diabetes mellitus will be included. The primary outcomes of this analysis will be overall mortality, cardiovascular mortality, and major cardiovascular events. Diabetic microangiopathy will be a secondary outcome. Adverse events, hypoglycemia, weight evolution, bariatric surgery, and discontinuation of the treatment will also be recorded. Each drug will be analyzed according to its therapeutic class: biguanide, alpha‐glucosidase inhibitors, sulfonylureas, glitazones, glinides, insulin, DPP‐4 inhibitors, GLP‐1 analogs, and gliflozins. The treatment effect of each drug class will be compared using pairwise meta‐analysis and a Bayesian random model network meta‐analysis. Sensitivity analyses will be conducted according to the quality of the studies and the glycemic control. The report will follow the PRISMA checklist for network meta‐analysis. Results of the search strategy and of the study selection will be presented in a PRISMA compliant flowchart. The treatment effects will be summarized with odds ratio (OR) estimates and their 95% credible intervals. A ranking of the drugs will be proposed. Our network meta‐analysis should allow a clinically relevant ranking of the contemporary antidiabetic drugs.     

Salvage therapy for acute myeloid leukemia with fludarabine,cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G‐CSF

The current salvage therapies for relapsed/refractory acute myeloid leukemia (AML) are unsatisfactory. Over the past 7 years, we have used two salvage regimens: fludarabine, cytarabine, and idarubicin with (FLAG‐IM) or without gemtuzumab ozogamicin (GO) (9 mg/m² on Day 8) (FLAG‐I) in relapsed/refractory AML. Three‐quarters of patients also received concurrent G‐CSF. Seventy‐one patients were treated, 23 with FLAG‐I and 48 with FLAG‐IM. The median duration of follow‐up was 30.6 months. The treatment groups were well balanced with median ages of 48 years (range 18–70) and 47 years (range 20–68), unfavorable cytogenetics in 57% and 35%, prior allogeneic stem cell transplant in 43% and 42%, and CR1 duration <1 year in 60% and 67%, respectively, for FLAG‐I and FLAG‐IM. The complete remission (CR) rate in the FLAG‐I group was 39% with an additional 13% achieving a CRp [overall response rate (ORR) 52%]; the CR rate in the FLAG‐IM group was 29% with an additional 27% achieving a CRp (ORR 56%). The median duration of response (DOR; 16.8 vs. 8.3 months), event‐free survival (EFS; 7.4 vs. 4.1 months), and overall survival (OS; 8.8 vs. 5.0 months) trended to favor FLAG‐I over FLAG‐IM. The patients who received G‐CSF concurrent with chemotherapy had superior overall response rate (ORR; 62% vs. 29%, P = 0.026), median EFS (6.2 vs. 3.4 months, P = 0.010), and OS (8.8 vs. 3.9 months, P = 0.004) when compared with those who sequentially received G‐CSF and chemotherapy, regardless of chemotherapy regimen. The addition of GO, at this dose and schedule, to FLAG‐I failed to improve the outcomes in patients with relapsed/refractory AML. The patients who received G‐CSF concurrently with chemotherapy had improved outcomes. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

Cost‐of‐illness of chronic leg ulcers in Germany

Chronic wounds are important because of their frequency, their chronicity and high costs of treatment. However, there are few primary data on the cost‐of‐illness in Germany. The aim was to determine the cost‐of‐illness of venous leg ulcers (VLU) in Germany. Prospective cost‐of‐illness study was performed in 23 specialised wound centres throughout Germany. Direct, medical, non medical and indirect costs to the patient, statutory health insurers and society were documented. Thereover, health‐related quality of life (QoL) was recorded as intangible costs using the Freiburg quality of life assessment for wounds (FLQA‐w, Augustin). A total of 218 patients (62.1% female) were recruited consecutively. Mean age was 69.8 ± 12.0 years. The mean total cost of the ulcer per year and patient was € 9569, [ € 8658.10 (92%) direct and € 911.20 (8%) indirect costs]. Of the direct costs, € 7630.70 was accounted for by the statutory health insurance and € 1027.40 by the patient. Major cost factors were inpatient costs, outpatient care and non drug treatments. QoL was strikingly reduced in most patients. In Germany, VLU are associated with high direct and indirect costs. As a consequence, there is a need for early and qualified disease management. Deeper‐going cost‐of‐illness‐studies and cost‐benefit analyses are necessary if management of chronic wounds is to be improved.     

Histogram analysis of MR imaging-derived cerebral blood volume maps： combined glioma grading and identification of low-grade oligodendroglial subtypes

BACKGROUND AND PURPOSE： Inclusion of oligodendroglial tumors may confound the utility of MR based glioma grading. Our aim was, first, to assess retrospectively whether a histogram-analysis method of MR peifusion images may both grade gliomas and differentiate between low-grade oligodendroglial tumors with or without loss of heterozygosity （LOH） on 1p/19q and, second, to assess retrospectively whether low-grade oligodendroglial subtypes can be identified in a population of patients with high-grade and low-grade astrocytic and oligodendroglial tumors.