Effects of a pre-visit educational website on information recall and needs fulfilment in breast cancer genetic counselling, a randomized controlled trial

INTRODUCTION: Pre-visit education which helps counselees to prepare for their first visit for breast cancer genetic counseling might enhance information recall and needs fulfilment. This study assessed the effects of a pre-visit website with tailored information and question prompt sheet (QPS), named E-info gene(ca). METHODS: A total of 197 counselees were randomized to receive usual care (UC) or UC plus E-info gene(ca). All counselees completed a pre- and post-visit questionnaire and visits were videotaped. We studied effects on counselees' information recall, knowledge about breast cancer and heredity, fulfillment of needs, risk perception alignment, anxiety and perceived personal control, using multilevel regression analyses. RESULTS: Intent-to-treat analysis showed that counselees in the intervention group (n = 103) had higher levels of recall of information from the consultation (β = .32; confidence interval (CI): .04 to .60; P = .02; d = .17) and post-visit knowledge of breast cancer and heredity (β = .30; CI: .03 to .57; P = .03) than counselees in the UC group (n = 94). Also, intervention group counselees reported better fulfilment of information needs (β = .31; CI: .03 to .60; P = .03). The effects of the intervention were strongest for those counselees who did not receive an indication for DNA testing. Their recall scores showed a larger increase (β = .95; CI: .32 to 1.59; P = .003; d = .30) and their anxiety levels dropped more in the intervention compared to the UC group (β = -.60; CI: -1.12 to -.09; P = .02). No intervention effects were found after the first visit on risk perception alignment or perceived personal control. CONCLUSIONS: This study shows that pre-counseling education, using tailored information technology, leads to more effective first visits for breast cancer genetic counseling, in particular for counselees who received no indication for DNA testing and, therefore, had no indication for a second visit. Future study should focus on the effects of a pre-visit website on the outcomes after a complete series of visits. TRIAL REGISTRATION: Dutch Trial Register ISRCTN82643064

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

The dynameomics entropy dictionary: a large-scale assessment of conformational entropy across protein fold space

YesMolecular dynamics (MD) simulations contain considerable information with regard to the motions and fluctuations of a protein, the magnitude of which can be used to estimate conformational entropy. Here we survey conformational entropy across protein fold space using the Dynameomics database, which represents the largest existing dataset of protein MD simulations for representatives of essentially all known protein folds. We provide an overview of MD-derived entropies accounting for all possible degrees of dihedral freedom on an unprecedented scale. Although different side chains might be expected to impose varying restrictions on the conformational space that the backbone can sample, we found that the backbone entropy and side chain size are not strictly coupled. An outcome of these analyses is the Dynameomics Entropy Dictionary, the contents of which have been compared with entropies derived by other theoretical approaches and experiment. As might be expected, the conformational entropies scale linearly with the number of residues, demonstrating that conformational entropy is an extensive property of proteins. The calculated conformational entropies of folding agree well with previous estimates. Detailed analysis of specific cases identify deviations in conformational entropy from the average values that highlight how conformational entropy varies with sequence, secondary structure, and tertiary fold. Notably, alpha-helices have lower entropy on average than do beta-sheets, and both are lower than coil regions.National Institutes of Health, US Department of Energy Office of Biological Research, National Energy Research Scientific Computing Center, Swedish Research Council, Knut and Alic Wallenberg Foundatio

Effect of voluntary waiting period on metabolism of dairy cows during different phases of the lactation.

An extended calving interval (CInt) by extending the voluntary waiting period (VWP) could be associated with altered metabolism in dairy cows. The aim of this study was first to evaluate the effects of VWP on metabolism and body condition during the first 305 days after the first calving in the experiment (calving 1), around the end of the VWP, and during pregnancy (280 d before calving 2). Second, the effects of the VWP on metabolism were determined from 2 wk before until 6 wk after calving 2. Third, individual cow characteristics were used to predict milk production and body condition of cows after different VWP. Holstein-Friesian cows (N=154, 41 primiparous (PP), 113 multiparous (MP)) were blocked for parity, milk production, and lactation persistency, randomly assigned to a VWP of 50, 125, or 200 days (VWP50, VWP125, or VWP200) and followed from calving 1 until 6 wk after calving 2. In the first 6 wk after calving 1 and from 2 wk before until 6 wk after calving 2, weekly plasma samples were analyzed for non-esterified fatty acids (NEFA), β-hydroxybutyrate, glucose, insulin, and insulin-like growth factor 1 (IGF-1). From wk 7 after calving 1 until 2 wk before calving 2, insulin and IGF-1 were analyzed every 2 wk. Fat- and protein-corrected milk (FPCM) and body weight (BW) gain were measured weekly. Cows were divided in two parity classes based on calving 1 (PP and MP) and remained in these classes after calving 2. During pregnancy, MP cows in VWP200 had greater plasma insulin and IGF-1 concentration and lower FPCM compared with MP cows in VWP125 (insulin: 18.5 vs 13.9 µU/mL, CI 13.0 - 19.7, P<0.01; IGF-1: 198.5 vs 175.3 ng/mL ± 5.3, P=0.04; FPCM: 22.6 vs 30.0 kg/d ± 0.8, P<0.01) or VWP50 (insulin: 15.8 µU/mL, P<0.01; IGF-1: 178.2 ng/mL, P<0.01; FPCM: 26.6 kg/d, P<0.01) and had a greater daily BW gain compared with cows in VWP50 (3.6 vs 2.5 kg/d ± 0.2; P<0.01). After calving 2, MP cows in VWP200 had greater plasma NEFA concentration (0.41 mmol/L) compared with MP cows in VWP125 (0.30 mmol/L, P=0.04) or VWP50 (0.26 mmol/L, P<0.01). For PP cows, the VWP did not affect FPCM or body condition during the first lactation in the experiment, or metabolism after calving 2. Independent of the VWP, higher milk production and lower body condition before insemination were associated with higher milk production and lower body condition at the end of the lactation. Variation in these characteristics among cows could call for an individual approach for an extended VWP

Impaired myocardial function does not explain reduced left ventricular filling and stroke volume at rest or during exercise at high altitude

Impaired myocardial systolic contraction and diastolic relaxation have been suggested as possible mechanisms contributing to the decreased stroke volume (SV) observed at high altitude (HA). To determine whether intrinsic myocardial performance is a limiting factor in the generation of SV at HA, we assessed left ventricular (LV) systolic and diastolic mechanics and volumes in 10 healthy participants (aged 32 ± 7; mean ± SD) at rest and during exercise at sea level (SL; 344 m) and after 10 days at 5,050 m. In contrast to SL, LV end-diastolic volume was ∼19% lower at rest (P = 0.004) and did not increase during exercise despite a greater untwisting velocity. Furthermore, resting SV was lower at HA (∼17%; 60 ± 10 vs. 70 ± 8 ml) despite higher LV twist (43%), apical rotation (115%), and circumferential strain (17%). With exercise at HA, the increase in SV was limited (12 vs. 22 ml at SL), and LV apical rotation failed to augment. For the first time, we have demonstrated that EDV does not increase upon exercise at high altitude despite enhanced in vivo diastolic relaxation. The increase in LV mechanics at rest may represent a mechanism by which SV is defended in the presence of a reduced EDV. However, likely because of the higher LV mechanics at rest, no further increase was observed up to 50% peak power. Consequently, although hypoxia does not suppress systolic function per se, the capacity to increase SV through greater deformation during submaximal exercise at HA is restricted. during initial exposure to hypobaric hypoxia at high altitude (HA), cardiac output for a given absolute workload is increased to compensate for a lower arterial oxygen content before returning to baseline levels with acclimatization (8). However, after 2-5 days of acclimatization, the required cardiac output is generated through a lower stroke volume (SV) and higher heart rate (38). The reduced SV is suggestive of either lower ventricular filling, potentially caused in part by an impaired myocardial relaxation, or impaired ejection secondary to systolic contractile dysfunction. There is, however, a paucity of data in humans supporting a direct effect of hypoxia on myocardial function at HA (25, 41). The suggestion that hypoxia may impair myocardial systolic function during exercise was proposed nearly 50 years ago (3) and has been revisited more recently (27–29). Negative inotropic effects of hypoxia (arterial oxygen tension of 44 mmHg) have been shown in intact animal models (39) and isolated myocardial fibers under severe hypoxia (1% O2) (33). Exercise training under hypobaric hypoxia is also associated with altered mechanical properties at a cellular level in rodents (9), although chronic hypoxia alone did not decrease myofilament sensitivity to calcium. However, in contrast to animal studies, data in humans indicate that systolic function is maintained or enhanced at HA. For example, Suarez et al. (37) reported the maintenance of systolic function after gradual decompression to a barometric pressure of 282 mmHg, a finding that was subsequently confirmed by numerous investigations during acute and prolonged hypoxic exposure (6, 10, 12, 23, 31). However, of these studies, only Suarez et al. (37) investigated systolic function during light exercise (60 W), where function appeared to be maintained. It is not known whether systolic function is maintained at higher exercise intensities. It has also been speculated that reduced oxygen availability may impair diastolic relaxation at HA (15, 18) and thus explain the decreased left ventricular (LV) end-diastolic volume (EDV) commonly observed (2, 6, 18). However, despite numerous studies reporting a decrease in plasma volume and altered transmitral filling patterns (2, 6, 20), myocardial relaxation was only previously investigated during hypoxia in dogs (15), and no data exist examining LV relaxation during exercise at high altitude. By using sensitive, noninvasive imaging techniques (two-dimensional speckle tracking), it is now possible to examine the LV deformation mechanics (strain, twist, and untwist velocity) that underpin LV systolic and diastolic function. LV strain and twist have been shown to be sensitive measures of global and regional myocardial function, and reveal subclinical dysfunction in patients where ejection fraction is unchanged (16, 22). In addition, diastolic LV untwist velocity correlates well with invasive measures of LV stiffness and provides a temporal link between relaxation and the development of intraventricular pressure gradients (30, 43). Therefore, examination of LV mechanics at HA may determine whether the decreased SV observed at HA is dependent on impaired myocardial relaxation and/or myocardial contractile dysfunction or confirm previous findings of preserved ventricular function during exercise (37). We therefore assessed systolic and diastolic ventricular mechanics during incremental exercise at sea level and HA to examine whether impaired myocardial relaxation or systolic dysfunction explains the previously reported reduction in SV at HA. We hypothesized that at HA, 1) ventricular filling would be lower at rest and during exercise and would be accompanied by a reduction in untwist velocity and 2) systolic mechanics would be impaired during exercise at HA

Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe

Aims/hypothesis: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. Methods: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. Results: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24–28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35–37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. Conclusions/interpretation: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies

Udder health of dairy cows with an extended voluntary waiting period from calving until the first insemination

This study aimed to evaluate the effect of an extended voluntary waiting period (VWP) on SCC, SCC elevations and clinical mastitis incidence during the complete lactation and the first 6 weeks of the next lactation. Holstein-Friesian dairy cows ( N = 154) were blocked for parity, expected milk yield, calving season and breeding value for persistency and were randomly distributed across 3 VWP (50, 125, or 200 d: VWP-50, VWP-125, VWP-200). Cows were monitored from calving until 6 weeks into the next lactation, or until culling. An elevation of SCC in milk was defined as SCC in milk ≥200 000 cells/ml after two previous weeks with SCC < 200 000 cells/ml. Over the complete lactation, extending the VWP did not affect SCC elevations and the occurrence of clinical mastitis per lactation or per cow per year. There was no clear effect of VWP length on SCC in the complete lactation, except that multiparous cows in VWP-125 had a higher SCC compared with multiparous cows in VWP-50. Dry-off antibiotic usage per cow per year was lower in VWP-200 compared with VWP-50 for multiparous cows. In the first 6 weeks of the next lactation, cows in VWP-200 had a higher SCC compared with cows in VWP-50, with no effect of VWP on the number of elevations of SCC or the occurrence of clinical mastitis. Extending the VWP may therefore be used to reduce the frequency of transition periods and the associated use of dry-cow antibiotics, with limited impact on udder health, and a similar occurrence of SCC elevations and clinical mastitis per year

Quality assurance guidelines for superficial hyperthermia clinical trials: II. Technical requirements for heating devices

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle