The psychology of ‘regrettable substitutions’: examining consumer judgements of Bisphenol A and its alternatives

Bisphenol A is a chemical used to make certain types of plastics and is found in numerous consumer products. Because scientific studies have raised concerns about Bisphenol A’s potential impact on human health, it has been removed from some (but not all) products. What many consumers do not know, however, is that Bisphenol A is often replaced with other, less-studied chemicals whose health implications are virtually unknown. This type of situation is known as a potential ‘regrettable substitution’, because the substitute material might actually be worse than the material that it replaces. Regrettable substitutions are a common concern among policymakers, and they are a real-world manifestation of the tension that can exist between the desire to avoid risk (known possible consequences that might or might not occur) and ambiguity (second-order uncertainty), which is itself aversive. In this article, we examine how people make such trade-offs using the example of Bisphenol A. Using data from Study 1, we show that people have inconsistent preferences towards these alternatives and that choice is largely determined by irrelevant contextual factors such as the order in which the alternatives are evaluated. Using data from Study 2, we further demonstrate that when people are informed of the presence of substitute chemicals, labelling the alternative product as ‘free’ of Bisphenol A causes them to be significantly more likely to choose the alternative despite its ambiguity. We discuss the relevance of these findings for extant psychological theories as well as their implications for risk, policy and health communication.     

Prognosis of Mild Cognitive Impairment in General Practice: Results of the German AgeCoDe Study

PURPOSE

The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients).

METHODS

We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis.

RESULTS

Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis.

CONCLUSIONS

In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.     

基于CYP3A4酶探讨灯盏花素对洛伐他汀的药动学的影响及机制

目的 探究灯盏花素与洛伐他汀联用对大鼠体内药动学的影响,从代谢酶的角度揭示灯盏花素对洛伐他汀药动学产生影响的机制。方法 采用探针药物法及RT-HPLC法测定咪达唑仑在肝微粒体孵育体系中的浓度,评价灯盏花素与洛伐他汀联用对CYP3A4酶活性的影响。通过RT-PCR反应来检测CYP3A4酶mRNA基因表达,采用Western blot法,从蛋白翻译水平上分析灯盏花素与洛伐他汀联用对大鼠肝脏CYP3A4蛋白表达的影响。结果 洛伐他汀与灯盏花素联合用药后,洛伐他汀在大鼠体内的血药浓度显著升高,从0.39 mg?L-1 上升到1.08 mg?L-1 ,清除率从3.36L?h-1?kg-1降低到1.08L?h-1?kg-1,药物半衰期从5.0h延长到6.2h,联合给药后洛伐他汀的AUC从2.42mg?L-1?h-1上升到4.22mg?L-1?h-1。洛伐他汀组与空白组比较CYP3A4酶活性均没有明显变化;灯盏花素组及灯盏花素联合洛伐他汀组与空白组比较发现均抑制CYP3A4酶活性;灯盏花素与灯盏花素联合洛伐他汀组CYP3A4酶mRNA 表达量均较空白组显著降低;CYP3A4酶蛋白含量结果表明,洛伐他汀组与灯盏花素联合洛伐他汀组与空白组比较CYP3A4酶蛋白含量均没有明显变化。结论 洛伐他汀与灯盏花素联用,灯盏花素通过抑制其基因转录水平抑制CYP3A4的活性,使大鼠体内药动学过程发生变化,洛伐他汀药物的代谢减慢。     

Heat Stress is Associated with Reduced Health Status in Pulmonary Arterial Hypertension: A Prospective Study Cohort

Background

Summer heat waves with temperature extremes are becoming more frequent with growing numbers in morbidity and mortality in patients with respiratory diseases. The aim of this study was to evaluate the ramifications of heat stress (temperature >25 °C) on the health status of patients with pulmonary arterial hypertension (PAH).

Methods

Fifteen patients with PAH (mean age = 66.7 ± 5.2 years) continuously wore an accelerometer from April 1 to September 30, 2011, and their daily step count was recorded. In addition, patients kept a diary to record data on seven standardized questions regarding their daily symptoms. Echocardiography, 6-minute walk test, NTproBNP, and Modified Medical Research Council Scale (MMRC) were assessed at baseline and at the end of the study after 6 months.

Results

On heat-stress days, patients showed significantly more symptoms and lower total steps/day compared to thermal comfort days (3,995 ± 2,013 steps/day vs. 5,567 ± 2,434 steps/day, respectively; P < 0.001). There was a significant negative correlation between total steps/day and Temp_max (R = ?0.47; P < 0.001) and humidity (R = ?0.34; P < 0.001). A significant positive correlation was found between daily symptoms and Temp_max (R = +0.79; P < 0.001) and humidity (R = +0.23; P < 0.001).

Conclusions

Heat stress is associated with a compromised clinical status in patients with PAH. Adaptation strategies must be implemented to prevent heart-related morbidity, including therapeutic adjustments and adequate room cooling in the patient’s home and at the hospital.     

Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy

Background

Despite extensive translational research, no validated biomarkers predictive of bevacizumab treatment outcome have been identified.

Methods

We performed a meta-analysis of individual patient data from six randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and gastric cancer to explore the potential relationships between 195 common genetic variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab treatment outcome.

Results

The analysis included 1,402 patients (716 bevacizumab-treated and 686 placebo-treated). Twenty variants were associated (P < 0.05) with progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4 variants in EPAS1 survived correction for multiple testing (q < 0.05). Genotype-by-treatment interaction tests revealed that, across these 20 variants, 3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were potentially predictive (P < 0.05), but not resistant to multiple testing (q > 0.05). A weak genotype-by-treatment interaction effect was also observed for rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05). Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci derived from lymphoblastoid cell lines, indicating that they affect the expression levels of their respective gene.

Conclusions

This large genetic analysis suggests that variants in VEGF-A, EPAS1, IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment outcome across tumor types. Although these associations did not survive correction for multiple testing in a genotype-by-interaction analysis, they are among the strongest predictive effects reported to date for genetic variants and bevacizumab efficacy.     

Periprosthetic bone mineral density after total hip arthroplasty with an AMIStem or Quadra femoral component performed by a minimally invasive anterior approach (AMIS): a prospective randomized clinical dual-energy X-ray absorptiometry study

Introduction

This prospective 12 months of dual-energy X-ray absorptiometry (DEXA) study evaluated differences in periprosthetic bone mineral density in 40 patients undergoing cementless total hip arthroplasty (THA) by a minimally invasive anterior approach (AMIS), using Medacta AMIStem or Quadra stems. Both stems are straight rectangular. AMIStem shows reduced lateral flare and length in comparison to Quadra.

Objectives

The main goal of the study is to verify if bone mineral density is equivalent following THA with the AMIStem and Quadra femoral components.

Methods

Forty patients were randomly allocated to the Quadra and AMIStem groups. Three patients were lost to follow-up because they moved to another town, and revision surgery was performed on one patient due to periprosthetic fracture after a car accident. Patients were examined clinically and underwent DEXA preoperatively and at 1 week, 6 weeks, 6 months, and 1 year after THA. Patients enrolled had no preexisting lower limb arthroplasty and no osteoporosis.

Results

Harris hip score increased significantly for Quadra stem 5.3?±?14.1 and AMIStem 41.0?±?13.4. The high-activity hip score increased significantly for Quadra stem 3.8 ±2.2 and AMIStem 4.1?±?2.4. Considering 0.15 mg/cm² as an acceptable difference, bone mineral density for AMIStem and Quadra groups was statistically equivalent. A limited remodeling process with slight bone loss in the proximal calcar region R7, as expected after implantation of uncemented components, was observed for both stems.

Conclusions

The study demonstrates that the two stems are statistically equivalent in all zones at all time points investigated.     

A new mutation in GJC2 associated with subclinical leukodystrophy

Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause Pelizaeus–Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype––hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype––a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance–junctional voltage (G _j–V _j) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes.