Decision making in treatment of symptomatic severe aortic stenosis: a survey study in Dutch heart centres.

AIM: To provide insight into the basic characteristics of decision making in the treatment of symptomatic severe aortic stenosis (SSAS) in Dutch heart centres with specific emphasis on the evaluation of frailty, cognition, nutritional status and physical functioning/functionality in (instrumental) activities of daily living [(I)ADL]. METHODS: A questionnaire was used that is based on the European and American guidelines for SSAS treatment. The survey was administered to physicians and non-physicians in Dutch heart centres involved in the decision-making pathway for SSAS treatment. RESULTS: All 16 Dutch heart centres participated. Before a patient case is discussed by the heart team, heart centres rarely request data from the referring hospital regarding patients' functionality (n = 5), frailty scores (n = 0) and geriatric consultation (n = 1) as a standard procedure. Most heart centres 'often to always' do their own screening for frailty (n = 10), cognition/mood (n = 9), nutritional status (n = 10) and physical functioning/functionality in (I)ADL (n = 10). During heart team meetings data are 'sometimes to regularly' available regarding frailty (n = 5), cognition/mood (n = 11), nutritional status (n = 8) and physical functioning/functionality in (I)ADL (n = 10). After assessment in the outpatient clinic patient cases are re-discussed 'sometimes to regularly' in heart team meetings (n = 10). CONCLUSIONS: Dutch heart centres make an effort to evaluate frailty, cognition, nutritional status and physical functioning/functionality in (I)ADL for decision making regarding SSAS treatment. However, these patient data are not routinely requested from the referring hospital and are not always available for heart team meetings. Incorporation of these important data in a structured manner early in the decision-making process may provide additional useful information for decision making in the heart team meeting.

Treatments of osteoporosis increase bone material strength index in patients with low bone mass.

Effects on bone material properties of two-year antiosteoporotic treatment were assessed using in vivo impact microindentation (IMI) in patients with low bone mineral density (BMD) values. Antiresorptive treatment, in contrast to vitamin D ± calcium treatment alone, induced BMD-independent increases in bone material strength index, measured by IMI, the magnitude of which depended on pretreatment values. INTRODUCTION: Bone material strength index (BMSi), measured by IMI in vivo, is reduced in patients with fragility fractures, but there is no information about changes in values during long-term therapy. In the present study, we assessed changes in BMSi in patients receiving antiosteoporotic treatments for periods longer than 12 months. METHODS: We included treatment-naive patients with low bone mass who had a BMSi measurement with OsteoProbe® at presentation and consented to a repeat measurement after treatment. RESULTS: We studied 54 patients (34 women), median age 58 years, of whom 30 were treated with bisphosphonates or denosumab (treatment group) and 24 with vitamin D ± calcium alone (control group). There were no differences in clinical characteristics between the two groups with the exception of a higher number of previous fragility fractures in the treatment group. Baseline hip BMD and BMSi values were lower in the treatment group. After 23.1 ± 6.6 months, BMSi increased significantly in the treatment group (82.4 ± 4.3 vs 79.3 ± 4.1; p < 0.001), but did not change in the control group (81.5 ± 5.2 vs 82.2 ± 4.1; p = 0.35). Changes in BMSi with antiresorptives were inversely related with baseline values (r = - 0.43; p = 0.02) but not with changes in BMD. Two patients in the control group with large decreases in BMSi values sustained incident fractures. CONCLUSION: In patients at increased fracture risk, antiresorptive treatments induced BMD-independent increases in BMSi values, the magnitude of which depended on pretreatment values.

Towards a more circular economy for WEEE plastics - Part A: Development of innovative recycling strategies.

This two paper series describes a method to develop and evaluate innovative recycling strategies for WEEE plastics. Part A presents a SWOT analysis of a new dismantling based recycling process of plastic components and the integration in an existing post-shredder separation recycling facility. Subsequently, recycling strategies are developed and the economic potential is evaluated. Part B investigates the technical feasibility of the recycling strategies. As a case study the dismantling of LCD TV plastic back cover housings is taken. First, the advantages and disadvantages of the new process and the main external factors based on the market for recycled plastics and the waste material input are discussed on industrial level. Subsequently, five recycling strategies are developed: Strategy (1) produces recycled granulates with the dismantling process for direct re-application in electronic products, strategy (2) recycles plastics for the use as carrier materials for flame retardant masterbatches, strategy (3) blends the recycled plastic with post-shredder recyclates for material upgrading, strategy (4) recycles the plastics with the post-shredder process and strategy (5) thermally treats plastics. Finally, the economic evaluation shows that the special engineering plastics used for LCD TV back covers have very high virgin prices up to 5 € per kg. The implementation of the new process indicates a significant potential for value recovery based on plastics that would otherwise be incinerated or downcycled.

Towards a more circular economy for WEEE plastics - Part B: Assessment of the technical feasibility of recycling strategies.

This two paper series describes a method to develop and evaluate new recycling strategies for WEEE plastics. Part A presents a SWOT analysis that leads to five recycling strategies for the optimal integration of new dismantling based recycling processes for plastic components in an established post-shredder separation infrastructure. In this paper the technical feasibility of the strategies is demonstrated by means of LCD TV back cover housings. The component recycling is shown to produce recycled PC/ABS with phosphorous flame retardants suitable for direct re-application in electronic products. The high quality is characterized by a good mechanical and aesthetical properties as well as a recovered flammability. HIPS with brominated flame retardants was recycled to produce masterbatches. The technical feasibility of this strategy was proven by mechanical and flammability testing. However, the presence of deca-BDE requires this material to be incinerated. A combination of EU legislation research and forecasting shows that the origin of this flame retardant are TV models produced before 2008 and restricted concentrations still need to be expected for decades to come. Further, a blending strategy of HIPS/PPE is shown to improve the mechanical properties of post-shredder recycled HIPS. The evaluation of refeeding ABS/PMMA into the post-shredder recycling process of ABS indicates only partial compatibility. Further, complications due to density differences make this strategy more suitable for polymers that are already commercially recycled such as ABS and HIPS. Colour is identified as a key requirements that limits the use of WEEE plastics in high-quality products.

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy.

Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation.

Optimized robotic setup for automated active thermography using advanced path planning and visibility study.

In-line inspection of advanced components remains a challenging task in industry. The authors will describe an automated methodology that uses numerical simulations to automatically determine the best set of experimental parameters to inspect the structure on defects using active thermography. The inspection is performed using a robotic arm and advanced path-planning tools to determine the optimal positions of the measurement points and excitation points. During the path planning, the directional emissivity is considered for the complex surface, and a minimization of the amount of measurement points is performed. The numerical simulation optimization used a genetic algorithm and spline regression model to optimize the heat power, robot speed, camera frame rate, and excitation timing to fulfill the automatic inspection.

Reliability and correlation analysis of computed methods to convert conventional 2D radiological hindfoot measurements to a 3D setting using weightbearing CT.

PURPOSE: The exact radiographic assessment of the hindfoot alignment remains challenging. This is reflected in the different measurement methods available. Weightbearing CT (WBCT) has been demonstrated to be more accurate in hindfoot measurements. However, current measurements are still performed in 2D. This study wants to assess the use of computed methods to convert the former uniplanar hindfoot measurements obtained after WBCT towards a 3D setting. METHODS: Forty-eight patients, mean age of 39.6 ± 13.2 years, with absence of hindfoot pathology were included. A WBCT was obtained, and images were subsequently segmented and analyzed using computer-aided design operations. In addition to the hindfoot angle (HA), other ankle and hindfoot parameters such as the anatomical tibia axis, talocalcaneal axis (TCA), talocrural angle, tibial inclination (TI), talar tilt, and subtalar vertical angle were determined in 2D and 3D. RESULTS: The mean [Formula: see text] was [Formula: see text] of valgus ± 3.2 and the [Formula: see text] was [Formula: see text] of valgus ± 6.5. These angles differed significantly from each other with a [Formula: see text]. The correlation between both showed to be good by [Formula: see text] Pearson correlation coefficient (r) of 0.72 ([Formula: see text]). The [Formula: see text] showed to be excellent when compared to the [Formula: see text], which was good. Similar findings were obtained in other angles. The highest correlation was seen between the [Formula: see text] and [Formula: see text] (r = 0.83, [Formula: see text]) and an almost perfect agreement in the [Formula: see text] ([Formula: see text]). CONCLUSION: This study shows a good and reliable correlation between the [Formula: see text] and [Formula: see text]. However, the [Formula: see text] overcomes the shortcomings of inaccuracy and provides valuable spatial data that could be incorporated during computer-assisted surgery to assess the multiplanar correction of a hindfoot deformity.

Measuring hindfoot alignment in weight bearing CT: A novel clinical relevant measurement method.

BACKGROUND: A precise pre-operative measurement of hindfoot malalignment is paramount to plan and obtain an accurate surgical correction. Hindfoot alignment is currently determined on standard weightbearing radiographs. However this is hampered by the superposition of the skeletal structures. Recent technology developed weightbearing cone beam CT to overcome this problem. The objective is to introduce a clinically relevant and reproducible method to measure hindfoot alignment on weightbearing CT. METHODS: Sixty malalignments of the hindfoot were divided in to two groups; group one containing a valgus alignment (n=30) and group two a varus alignment (n=30) of the hindfoot. Imaging techniques used were standard radiographs and a weightbearing CT (pedCAT®). Following angles were measured by two different authors: standard long axial hindfoot angle both on standard radiographs and on CT, clinical hindfoot, novel hindfoot angle, talar shift (distance from a neutral alignment), tibial inclination angle, talar tilt and subtalar vertical angle on CT. RESULTS: Hindfoot alignment angles showed to significantly differ from each other (P<0.001). The novel hindfoot alignment angle showed the highest correlation with the clinical measurement method. Correlation of this novel angle with the talar shift showed a Spearman's correlation coefficient=0.87. Interclass correlation coefficient of the novel hindfoot alignment angle=0.72 and was the highest among the hindfoot alignment angles. CONCLUSION: Weightbearing CT is allows to objectively assess hindfoot alignment. The proposed novel hindfoot alignment angle showed to be both clinically relevant and reproducible as compared to previous methods. The lateral tibiocalcaneal shift, on which the angle is highly correlated to, can help the surgeon in determining how much translation is necessary to obtain a neutral alignment during a calcaneal osteotomy. LEVEL OF EVIDENCE: Level III: retrospective cohort study.

Radiological and clinical outcome of arthroscopic labral repair with all-suture anchors.

PURPOSE: The aim of this study was to assess radiological and clinical outcome after arthroscopic all--suture anchor labral repair. METHOD: 20 patients treated for anterior and superior labral instability (mean age 29, range 14-51 years) were assessed at a minimum follow-up time of 1 year (mean 19 months ; range, 12-28 months). Postoperative MRI scans were assessed by 3 independent radiologists. The radiological appearance of bone at the anchor-site was judged by the presence of cyst formation, tunnel widening (> 2 mm) or bone edema. Clinical outcome analysis included standard follow-up and the Disabilities of the Arm, Shoulder and Hand score (DASH), Constant Shoulder score and the Western Ontario Shoulder Instability Index (WOSI). RESULT: All patients were available for follow-up. In total, 58 all-suture anchors were implanted. None of the patients displayed large cyst formation. Small cysts were found in two patients (2 anchors). Tunnel widening was apparent in 3 patients (3 anchors) with an average widening of 3.3 mm (range 3-4 mm). Bone edema at the anchor-site was seen in 6 patients (8 anchors). The remaining 9 patients (45 anchors) did not display reactive bone changes. Clinical outcomes showed a WOSI of 70.6, a DASH of 18.9 and a Constant score of 89.3, and no recurrence of instability. CONCLUSIONS: Satisfying radiological and clinical outcome was observed after arthroscopic instability surgery using all-suture anchors. Imaging revealed good labral healing without important bony reactions or the formation of large cysts at early follow-up. Level of evidence : IV Case series.

FOXP3 can modulate TAL1 transcriptional activity through interaction with LMO2.

T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1-complex is thought to have a pivotal role in the transformation of thymocytes and is associated with a differentiation block and self-renewal. The transcription factor Forkhead Box P3 (FOXP3) was recently described to be expressed in a variety of malignancies including T-ALL. Here we show that increased FOXP3 levels negatively correlate with expression of genes regulated by the oncogenic TAL1-complex in human T-ALL patient samples as well as a T-ALL cell line ectopically expressing FOXP3. In these cells, FOXP3 expression results in altered regulation of cell cycle progression and reduced cell viability. Finally, we demonstrate that FOXP3 binds LMO2 in vitro, resulting in decreased interaction between LMO2 and TAL1, providing a molecular mechanism for FOXP3-mediated transcriptional modulation in T-ALL. Collectively, our findings provide initial evidence for a novel role of FOXP3 as a tumor suppressor in T-ALL through modulation of TAL1 transcriptional activity.

[Contrast-induced nephropathy and mortality after contrast-based investigation]. / Contrastnefropathie en sterfte na contrastonderzoek.

OBJECTIVE: To evaluate the Dutch CBO guideline 'Preventive measures for iodine-based contrast investigations' in daily practice, and to assess one-year mortality post contrast exposure in patients at high risk of contrast-induced nephropathy (CIN). DESIGN: Prospective cohort study. METHOD: Between July 2011 and May 2013, 497 patients at high risk of CIN were prepared for elective iodine-based contrast investigations according to the Dutch CBO guideline. This group was followed up until May 2014 or, if applicable, until death. CIN incidence and reversibility, and mortality, were assessed. RESULTS: CIN occurred in 20 patients (4%). The incidence was highest in the group of patients with an estimated glomerular filtration rate (eGFR) < 30 ml/min per 1.73 m2 (9/84 patients). CIN was reversible within two months in 19 patients. None of the patients with CIN died during that period. One-year mortality post contrast exposure was 22.5% (median survival: 203 days). CONCLUSION: This cohort study shows a low incidence of CIN, which is largely reversible. Almost a quarter of the cohort died within a year post contrast exposure, not as the result of CIN but probably due to comorbidities. Adherence to the current CBO guideline exposes patients with a reduced life expectancy to excessive preventive measures, while the occurrence of CIN is rare. These data warrant reconsideration of the current CBO guideline.

Biomarkers in outpatient heart failure management; Are they correlated to and do they influence clinical judgment?

AIMS: Heart failure (HF) management is complicated by difficulties in clinical assessment. Biomarkers may help guide HF management, but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied. We investigated the correlation between biomarkers and clinical signs and symptoms, the influence of patient characteristics and comorbidities on New York Heart Association (NYHA) classification and the effect of using biomarkers on clinical evaluation. METHODS AND RESULTS: This post-hoc analysis comprised 622 patients (77 ± 8 years, 76 % NYHA class ≥3, 80 % LVEF ≤45 %) participating in TIME-CHF, randomising patients to either NT-proBNP-guided or symptom-guided therapy. Biomarker measurements and clinical evaluation were performed at baseline and after 1, 3, 6, 12 and 18 months. NT-proBNP, GDF-15, hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA, oedema, jugular vein distension and orthopnoea (ρ-range: 0.12-0.33; p < 0.01). NT-proBNP correlated more strongly to NYHA class in the NT-proBNP-guided group compared with the symptom-guided group. NYHA class was significantly influenced by age, body mass index, anaemia, and the presence of two or more comorbidities. CONCLUSION: In HF, biomarkers correlate only weakly with clinical signs and symptoms. NYHA classification is influenced by several comorbidities and patient characteristics. Clinical judgement seems to be influenced by a clinician's awareness of NT-proBNP concentrations.

Capacity of endometrial thickness measurement to diagnose endometrial carcinoma in asymptomatic postmenopausal women: a systematic review and meta-analysis.

OBJECTIVES: Measurement of endometrial thickness is an important tool in the assessment of women with postmenopausal bleeding, but the role of endometrial thickness measurement by ultrasound in asymptomatic women is unclear. The aims of this study were to determine: (1) the normal endometrial thickness measured by ultrasonography, (2) the prevalence of serious endometrial pathology and (3) the sensitivity and specificity of endometrial thickness measurement by transvaginal ultrasonography (TVS) for diagnosing premalignant and malignant endometrial disease in asymptomatic postmenopausal women. METHODS: A MEDLINE and EMBASE search (from inception to January 2011) was performed. Articles reporting on endometrial thickness measurement in the diagnosis of endometrial carcinoma and atypical hyperplasia in asymptomatic postmenopausal women not using hormone replacement therapy (HRT) were selected. Endometrial thickness and the prevalence of endometrial (pre)malignancies were recorded. If possible, 2 × 2 tables were extracted. RESULTS: Thirty-two studies reporting on 11100 women were included. The estimated mean endometrial thickness was 2.9 mm (95% CI, 2.6-3.3 mm). The pooled estimated prevalences of endometrial carcinoma and atypical endometrial hyperplasia were 0.62% (95% CI, 0.42-0.82%) and 0.59% (95% CI, 0.22-0.96%), respectively. Summary estimates for sensitivity and specificity of TVS endometrial thickness measurement in the prediction of endometrial carcinoma were 0.83 (95% CI, 0.19-1.00) and 0.72 (95% CI, 0.23-0.95) for a 5-mm cut-off and 0.33 (95% CI, 0.04-0.85) and 0.94 (95% CI, 0.92-0.96) for a 6-mm cut-off. CONCLUSIONS: The results from this systematic review do not justify the use of endometrial thickness as a screening test for endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women not using HRT.

A theoretical study of the OH-initiated gas-phase oxidation mechanism of ß-pinene (C10H16): first generation products.

An extensive mechanism for the OH-initiated oxidation of ß-pinene up to the first-generation products was derived based on quantum chemical calculations, theoretical kinetics, and structure-activity relationships. The resulting mechanism deviates from earlier explicit mechanisms in several key areas, leading to a different product yield prediction. Under oxidative conditions, the inclusion of ring closure reactions of unsaturated alkoxy radicals brings the predicted nopinone and acetone yields to an agreement with the experimental data. Routes to the formation of other observed products, either speciated or observed as peaks in mass spectrometric studies, are also discussed. In pristine conditions, we predict significant acetone formation following ring closure reactions in alkylperoxy radicals; in addition, we predict some direct OH recycling in subsequent H-migration reactions in alkylperoxy radicals. The uncertainties on the key reactions are discussed. Overall, the OH-initiated oxidation of ß-pinene is characterized by the formation of a few main products, and a very large number of products in minor to very small yields.

Key factors influencing the implementation success of a home telecare application.

RATIONALE: The introduction of home telecare in healthcare organizations has shown mixed results in practice. The aim of this study is to arrive at a set of key factors that can be used in further implementation of video communication. We argue that key factors are mainly found in the organizational climate for home telecare implementation, the characteristics of the implementation strategy and the available technology. METHODS: Interviews were conducted in three care organizations with 27 respondents of different levels within and outside the organization. Implementation determinants, based on earlier research, were used as a categorization framework for the interviews. RESULTS: We found that most prominent factors influencing implementation outcomes relate to the stability of the technical and the external environment and the alignment of organization, goals and implementation strategy. CONCLUSION: Because of the experimental nature of implementing video communication, attention to telecare influencers has been inconsistent and disorganized but it is becoming increasingly important. According to the respondents, a champion-led roll-out is imperative for implementation in order to advance to the next stage in home telecare and to organize services for substitution of care.

[Problems and needs of informal caregivers of persons with dementia: a comparison between the initial stage and subsequent stages of the illness process]. / Problemen en wensen van mantelzorgers van mensen met dementie: een vergelijking tussen de beginfase en latere fasen in het ziekteproces.

This paper investigates whether informal caregivers of persons who have had symptoms of dementia for less than a year, differ from informal caregivers of persons in subsequent stages of dementia. Differences will be investigated in (a) problems experienced in the provision of informal care, (b) the use of ambulatory types of professional support, and (c) the need for additional professional support. Results are based on a survey among 1494 Dutch informal caregivers. Almost all informal caregivers experience problems in caring for a person with dementia, irrespective of the stage of the illness process. Their main problems concern dealing with changes in the behaviour of the person with dementia and dreading the person's admission to a nursing home. Informal caregivers of persons who have had symptoms of dementia for a longer period of time (> 1 year) also experience limitations in their social network. Most persons with dementia receive some kind of professional support. Still, the majority of informal caregivers indicate a need for additional professional support, mainly concerning advice and information. Limiting the available support options for persons with initial symptoms of dementia and their informal caregivers is therefore undesirable. Considering the need for additional support in the initial stage of dementia as well as in subsequent stages, persons with dementia and their informal caregivers should be supported during the entire illness process.

A structure-activity relationship for the rate coefficient of H-migration in substituted alkoxy radicals.

A framework is formulated for the development of a predictive structure-activity relationship for the temperature-dependent rate coefficients of H-migration in substituted alkoxy radicals. It is based on a multi-conformer transition state theory model, using quantum chemical characterizations of alkoxy radicals and their transition states for isomerisation. Using this framework, a SAR is then developed for the prediction of rate coefficients at 1 atm and T = 250-350 K, relative to a set of three reference reactions. The SAR covers 1,4-through 1,8-H-migration, as well as oxo- and hydroxy substitution in various positions relative to the radical oxygen and the migrating H.