Australian population data for the twenty Promega PowerPlex 21 short tandem repeat loci

This paper describes the analysis of population data typed using the Promega PowerPlex 21 multiplex for the three major sub populations within Australia. Samples from 1427 declared Australian Aboriginal, 546 Pure Aboriginals from the Northern Territory, 990 Asian, and 1707 Caucasian individuals representing were analysed. Departures from Hardy–Weinberg equilibrium (HWE) and linkage equilibrium (LE) were assessed using exact tests. The Aboriginal populations were shown to display significant departures from equilibrium. All four subpopulation databases are of suitable size for the purpose of estimating allele frequencies.     

Degradation of forensic DNA profiles

Selected profiles typed at the Promega PowerPlex 21 (PP21) loci were examined to determine if a linear or exponential model best described the relationship between peak height and molecular weight. There were fewer large departures from observed and expected peak heights using the exponential model. The larger differences that were observed were exclusively at the high molecular weight loci. We conclude that the data supports the use of an exponential curve to model peak heights versus molecular weight in PP21 profiles. We believe this observation will improve our ability to model expected peak heights for use in DNA interpretation software.     

Determination of the variables affecting mixed MiniFiler™ DNA profiles

The interpretation of mixed DNA profiles presents additional challenges for the forensic scientist. There has been a broad based call for transparency in the process of interpretation of all evidence including mixed DNA profiles. This interpretation is greatly facilitated by a sound understanding of the variability in peak heights for the two peaks of a heterozygote, in the sizes of stutter peaks and in the variability in peak heights across loci.This study examines single source and mixed DNA profiles to assess this variability. The relative variability in peak height between the two peaks of a heterozygote and in the peak heights across loci becomes greater as the peaks themselves become smaller. This is consistent with findings from other multiplexes. This variability appears larger in the MiniFiler™ system at 30 cycles than, for example, in the Identifiler™ system at 28 cycles and this difference is largely explained by the two extra cycles of amplification.Stutter peaks appear no larger in the MiniFiler™ system at 30 cycles than in the Identifiler™ system at 28 cycles.     

CT predictors of mortality in pathology confirmed ARDS

Objectives  

To identify CT findings that predict mortality in acute respiratory distress syndrome (ARDS) and to identify CT findings that differentiate diffuse alveolar damage (DAD) from DAD with prominent histopathological features of organizing pneumonia (DAD-OP).     

An integrated outsourcing solution at York Central Hospital

Canadian hospitals struggle to balance the need to increase and improve operational services and quality with diminishing resources. Many realize that sustaining their organization depends on how well they focus their resources and talents on their core business, clinical care delivery. Outsourcing of non-core, non-clinical support services is a solution for many organizations. Most often, this is put into action one service provider at a time. In 2007, however, York Central Hospital (YCH) implemented Sodexo's integrated Comprehensive Service Solutions (CSS) for all its support service functions. In doing so, YCH achieved significant improvements in patient and staff satisfaction rates, substantial cost savings through improved operational efficiency from process improvements and leveraging technology investments, and increased retail food revenue.     

Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh(0)-D) immune globulin

Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue hemorrhagic fever (DHF). An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF (see Saito et al., 2004, Clin Exp Immunol 138: 299-303; Mitrakul, 1979, Am J Trop Med Hyg 26: 975-984; and Boonpucknavig, 1979, Am J Trop Med Hyg 28: 881-884). The interim data of two randomized placebo controlled trials in patients (N = 47) meeting WHO criteria for dengue hemorrhagic fever (DHF) with severe thrombocytopenia (platelets < or = 50,000/mm(3)) reveal that the increase in platelet count with anti-D immune globulin (WinRho SDF), 50 microg/kg (250 IU/kg) intravenously is more brisk than the placebo group. The mean maximum platelet count of the anti-D-treated group at 48 hours was 91,500/mm(3) compared with 69,333/mm(3) in the placebo group. 75% of the anti-D-treated group demonstrated an increase of platelet counts > or = 20,000 compared with only 58% in the placebo group. These data suggest that treatment of severe thrombocytopenia accompanying DHF with anti-D may be a useful and safe therapeutic option.     

Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma

Targeting cytotoxic drugs to cancer cells using antibody-drug conjugates (ADCs), particularly those with stable linkers between the drug and the antibody, could be an effective cancer treatment with low toxicity. However, for stable-linker ADCs to be effective, they must be internalized and degraded, limiting potential targets to surface antigens that are trafficked to lysosomes. CD79a and CD79b comprise the hetrodimeric signaling component of the B-cell receptor, and are attractive targets for the use of ADCs because they are B-cell-specific, expressed in non-Hodgkin lymphomas (NHL), and are trafficked to a lysosomal-like compartment as part of antigen presentation. We show here that the stable-linker ADCs anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are capable of target-dependent killing of nonHodgkin lymphoma cell lines in vitro. Further, these 2 ADCs are equally effective as low doses in xenograft models of follicular, mantle cell, and Burkitt lymphomas, even though several of these cell lines express relatively low levels of CD79b in vivo. In addition, we demonstrate that anti-CD79b ADCs were more effective than anti-CD79a ADCs and that, as hypothesized, anti-CD79b antibodies downregulated surface B-cell receptor and were trafficked to the lysosomal-like major histocompatibility complex class II-positive compartment MIIC. These results suggest that anti-CD79b-MCC-DM1 and anti-CD79b-MC-MMAF are promising therapeutics for the treatment of NHL.     

Dalteparin vs low-dose unfractionated heparin for prophylaxis against clinically evident venous thromboembolism in acute traumatic spinal cord injury: a retrospective cohort study

Background:

When venous thromboembolism (VTE) includes deep-vein thrombosis (DVT) and pulmonary embolism (PE), patients with acute traumatic spinal cord injury (SCI) have the highest incidence of VTE among all hospitalized groups, with PE the third most common cause of death. Although low–molecular-weight heparin (LMWH) outperforms low-dose unfractionated heparin (LDUH) in other patient populations, the evidence in SCI remains less robust.

Objective:

To determine whether the efficacy for LMWH shown in previous SCI surveillance studies (eg, routine Doppler ultrasound) would translate into real-world effectiveness in which only clinically evident VTE is investigated (ie, after symptoms or signs present).

Methods:

A retrospective cohort study was conducted of 90 patients receiving LMWH dalteparin (5,000 U daily) or LDUH (5,000 U twice daily) for VTE prophylaxis after acute traumatic SCI. The incidence of radiographically confirmed VTE was primarily analyzed, and secondary outcomes included complications of bleeding and heparin-induced thrombocytopenia.

Results:

There was no statistically significant association (p = 0.7054) between the incidence of VTE (7.78% overall) and the type of prophylaxis received (LDUH 3/47 vs dalteparin 4/43). There was no significant differences in complications, location of VTE, and incidence of fatal PE. Paraplegia (as opposed to tetraplegia) was the only risk factor identified for VTE.

Conclusions:

There continues to be an absence of definitive evidence for dalteparin (or other LMWH) over LDUH as the choice for VTE prophylaxis in patients with SCI. Novel approaches to VTE prophylaxis are urgently required for this population, whose risk of fatal PE has not decreased over the last 25 years.     

Discordance between CT and angiography in the PIOPED II study

PURPOSE: To retrospectively evaluate the causes of discordant computed tomographic (CT)-angiographic readings from the Prospective Investigation of Pulmonary Embolism Diagnosis, or PIOPED, II study. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study. Of 1036 patients suspected of having pulmonary embolism who were examined with CT, 226 underwent angiography; 206 patients had concordant results and 20 had discordant results according to two independent readers. Of these 20 patients, 10 were men and 10 were women (mean age, 49 years). Among the 20 studies with discordant results, central readers identified seven cases as negative and 13 as positive for pulmonary embolism at CT; these findings were reversed at angiography. Side-by-side comparisons of discordant studies were performed in consensus. The time between CT and angiography and all locations of pulmonary embolism vascular territory were recorded. The McNemar binomial test was used. RESULTS: One patient had false-positive findings at angiography, 13 patients had false-negative findings at angiography, and two patients had false-negative findings at CT. Four patients had true-negative findings at CT; however, findings were positive for thrombus at angiography. The sensitivity for the detection of pulmonary embolism was 87% for CT and 32% for angiography (P=.007). The largest missed thrombus at angiography was subsegmental in eight patients, segmental in two patients, and lobar in three patients; at CT it was subsegmental in two patients. The mean time between CT and angiography was 40 hours+/-21 (standard deviation) (range, 10-97 hours). CONCLUSION: In the interval between CT and angiography, thrombi can remain the same, resolve, develop, or result from angiography.