Allelic drop-out probabilities estimated by logistic regression--further considerations and practical implementation

We discuss the model for estimating drop-out probabilities presented by Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of the model has demonstrated that the model is not perfect. However, the model is very useful for advanced forensic genetic work, where allelic drop-out is occurring. With this discussion, we hope to improve the drop-out model, so that it can be used for practical forensic genetics and stimulate further discussions. We discuss how to estimate drop-out probabilities when using a varying number of PCR cycles and other experimental conditions.     

The impact of shared decision making on time consumption and clinical decisions. A prospective cohort study

ObjectiveConcerns of increased time consumption and of the impact on clinical decisions may restrain doctors from shared decision making (SDM). This paper evaluates consultation length and decisions made when using an in-consult patient decision aid (PtDA).MethodsThis prospective cohort study compared an unexposed cohort with a cohort exposed to SDM and a PtDA in two preference-sensitive decision situations: invasive lung cancer diagnostics and adjuvant treatment for early breast cancer. Outcome measures were consultation length and decisions made.ResultsThe study included 261 consultations, 115 were in the SDM-exposed cohort. Consultations were inconsiderably longer in the SDM cohort; 2 min, 11 s (p = 0.2217) for lung cancer diagnostics and 3 min, 57 s (p = 0.1128) for adjuvant breast cancer treatment. In lung cancer diagnostics, consultation length became more uniform and decisions tended to become conservative after introduction of SDM. For adjuvant breast cancer, slightly more patients in the SDM cohort chose to decline treatment.ConclusionShared decision making did not take significantly longer time and led to slightly more conservative decisions.Practice implicationsSDM may be implemented without considerable impact on consultation length. The impact on clinical decisions depends mainly on the clinical situation.     

Cardiovascular Autonomic Neuropathy Is Associated With Macrovascular Risk Factors in Type 2 Diabetes: New Technology Used for Routine Large-Scale Screening Adds New Insight

Background:The objective was to identify the presence of cardiovascular autonomic neuropathy (CAN) in a cohort of individuals with diabetes in outpatient clinics from 4 different parts of Denmark and to explore the difference between type 1 and type 2 diabetes in relation to CAN.Methods:The DAN-Study is a Danish multicenter study focusing on diabetic autonomic neuropathy. Over a period of 12 months, 382 type 1 and 271 type 2 individuals with diabetes were tested for CAN. Patients were randomly recruited and tested during normal visits to outpatient clinics at 4 Danish hospitals. The presence of CAN was quantified by performing 3 cardiovascular reflex tests (response to standing, deep breathing, and valsalva). To describe possible associations, multivariate analysis with CAN as the dependent variable was performed.Results:The prevalence of CAN was higher among patients with type 2 diabetes (35%) compared to patients with type 1 diabetes (25%). Multivariate analysis revealed significant associations between CAN and different risk markers in the 2 populations. In type 1 diabetes patients CAN was associated with microalbuminuria (P < .001), macroalbuminuria (P = .011), simplex retinopathy (P < .001), proliferative retinopathy (P < .001), and peripheral neuropathy (P = .041). Among type 2 diabetes patients CAN was independently associated with high pulse pressure (P < .01), BMI (P = .006), and smoking (P = .025).Conclusion:In this cross-sectional observational study CAN was independently associated with microvascular complication in type 1, whereas in type 2 CAN was associated with macrovascular risk factors.     

Vanadate-induced Ca(2+) and Co(2+) uptake in human red blood cells

The vanadate-induced increase in passive uptake of calcium and cobalt and their interference were studied in human red cells using ⁴⁵Ca and ⁵⁷Co as tracers. Vanadate is a potent inhibitor of the Ca-pump in red cells, although in fed cells a residual pump activity remains that is highly significant compared to the passive influx, and even in cells that are both ATP-depleted and vanadate-treated the pump arrest is not complete. In the presence of vanadate the Ca^2 + uptake is increased due to inhibition of Ca-pump extrusion, but is further increased due to a vanadate-induced increment in passive influx. In order to measure the vanadate-induced increment in Ca^2 + influx, the total uptake in vanadate-treated cells is corrected for the basal influx, as recorded in ATP-depleted cells in the presence of tetrathionate (5 mM) that has been shown to eliminate the residual Ca-pump activity in ATP-depleted cells. The ⁵⁷Co uptake is also increased by vanadate. ⁵⁷Co is not transported by the Ca-pump, and hence the uptake in vanadate-treated cells can be directly compared to the basal uptake, both in fed and in ATP-depleted cells. The vanadate effect shows rapid onset and appears to be irreversible. The vanadate-induced increment in uptake of both ⁴⁵Ca and ⁵⁷Co is reduced by about 50% in ATP-depleted cells compared to fed cells, suggesting a metabolism- or SH-group-dependent component. The influx of both ⁴⁵Ca (in ATP-depleted cells) and ⁵⁷Co (in fed cells) increases with the vanadate concentration, with a similar K_½ (0.4 and 0.3 mM, respectively), and is nearly maximal at 5 mM vanadate. The vanadate-induced increment in influx of both ⁴⁵Ca and ⁵⁷Co increases with the extracellular concentration as a saturable function, with K_½ estimated at, respectively, 700 and 80 μM. In the case of ⁵⁷Co K_½ is similar in fed and in ATP-depleted cells. The vanadate-induced uptake of ⁴⁵Ca and of ⁵⁷Co shows interference. The uptake of ⁴⁵Ca is inhibited by Co^2 +, and the uptake of ⁵⁷Co is inhibited by Ca^2 +, although with an unexplained time course. The vanadate-induced uptake of ⁴⁵Ca and ⁵⁷Co are both inhibited, and to a similar degree, by the 1,4-dihydropyridine Ca^2 +-channel blocker nifedipine, although only at concentrations much higher than IC₅₀ for classical Ca-channels. The vanadate-induced increment in ⁵⁷Co uptake is electroneutral, in contrast to the basal uptake that is at least partially electrogenic. In experiments with resealed ghosts a vanadate-induced ⁵⁷Co uptake could not be detected. The vanadate-induced increment in ⁵⁷Co uptake amounts to nearly half the increment in ⁴⁵Ca uptake, both in fed and in ATP-depleted cells. It is speculated that the vanadate-induced Ca^2 + and Co^2 + uptake could be mediated by a putative common transporter, which appears to be separate and distinct from the putative common transporter for basal Ca^2 + and Co^2 + uptake.