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We investigate how students’ voices are enacted in reform processes and in research on reforms. Our theoretical stance on the concept of reform is performative and onto-epistemological; thus, we understand reforming as an entangled multiplicity, co-emerging and co-morphing. Reforming reconfigure what ‘is’ and intra-act with what is already there. The article focus on a reform of the Danish primary and secondary school. We work with three different cases, each with a different data-set, and analyse how research methodologies and findings in the field of reform research constitute ‘the student’ and ‘student voice’ as well as we look into dynamics of how reforms shape and change what counts as voices and how voices change and shape reforms. [ABSTRACT FROM AUTHOR]

The spatial architecture of signaling pathways and the interaction with cell size and morphology are complex, but little understood. With the advances of single cell imaging and single cell biology, it becomes crucial to understand intracellular processes in time and space. Activation of cell surface receptors often triggers a signaling cascade including the activation of membrane-attached and cytosolic signaling components, which eventually transmit the signal to the cell nucleus. Signaling proteins can form steep gradients in the cytosol, which cause strong cell size dependence. We show that the kinetics at the membrane-cytosolic interface and the ratio of cell membrane area to the enclosed cytosolic volume change the behavior of signaling cascades significantly. We suggest an estimate of average concentration for arbitrary cell shapes depending on the cell volume and cell surface area. The normalized variance, known from image analysis, is suggested as an alternative measure to quantify the deviation from the average concentration. A mathematical analysis of signal transduction in time and space is presented, providing analytical solutions for different spatial arrangements of linear signaling cascades. Quantification of signaling time scales reveals that signal propagation is faster at the membrane than at the nucleus, while this time difference decreases with the number of signaling components in the cytosol. Our investigations are complemented by numerical simulations of non-linear cascades with feedback and asymmetric cell shapes. We conclude that intracellular signal propagation is highly dependent on cell geometry and, thereby, conveys information on cell size and shape to the nucleus. [ABSTRACT FROM AUTHOR]

Factors driving the species richness and distribution of bryophytes are poorly studied and not well understood, particularly in grasslands. We analysed the occurrence of bryophyte species and variation in species richness across 674 plots (0.5 m × 0.5 m) in alvar vegetation (grassland on limestone pavement with thin or no soil) on Öland (Sweden) in relation to substrate characteristics and chemistry, inundation frequency, grazing pressure and geographical variables. We found 148 taxa, including 11 nationally red-listed ones. Species richness per plot was significantly associated with substrate type, positively associated with pH and grazing intensity, but negatively associated with soil depth. However, richness of species typical of, or restricted to, alvar habitats responded differently to richness of species more common in other habitats. Typical alvar species were favoured by high pH, shallow soil and low phosphate availability, while generalists preferred relatively low pH, higher phosphate availability and organic or mull soil types. Distance from the alvar margin had only weak effects. Concerning the effects on individual species and community composition, inundation frequency and pH were found to have the largest effects, although other factors (substrate type, soil depth, bare soil, bare stone, phosphate availability and grazing pressure) were more important for some individual species, stressing the importance of microsite variability and variability in management for regional species richness. From a conservation perspective, it is concluded that grazing is generally positive whilst factors increasing phosphate availability may disadvantage the typical alvar species, and proximity to the alvar margin is not a major problem. [ABSTRACT FROM AUTHOR]

Mosses (division Bryophyta) are characterized by the dominance of haploid, poikilohydric gametophytes, and relatively persistent sporophytes that are dependent on the gametophyte generation. Because they are poikilohydric, tend to be desiccation tolerant, and have primarily ectohydric water uptake mechanisms, the ecological requirements of mosses tend to differ from those of vascular plants. We review recent research on phylogenetic relationships and morphological and ecological diversity among mosses. Ancestral character state reconstructions illustrate the evolution of habitat preferences and the relationships between these and morphological variation. These reconstructions reveal the convergent evolution of both epiphytic and aquatic habitat preferences, as well as several reversals from epiphytic to other terrestrial habitats. Morphological character states connected to ectohydry, such as lack of water-conducting stem central strands, may be more prone to adaption driven by environmental conditions, while connections between endohydry and environmental conditions remain ambiguous and require further study. The distribution of the most elaborate endohydric water-conducting structures may be phylogenetically determined rather than resulting from adaptation to habitats. Among the early diverging lineages in the Bryophyta, shifts to cladocarpy may be connected to epiphytic lifestyles. We discuss ecological drivers of aspects of plant architecture including acrocarpous, pleurocarpous and cladocarpous perichaetial positions, and sporophytic reductions, the latter being common in dry, frequently disturbed terrestrial environments and in epiphytic habitats, but also occasionally found in aquatic habitats. [ABSTRACT FROM AUTHOR]

With a view to occupational effects of climate change, we performed a simulation study on the influence of different heat stress assessment metrics on estimated workability (WA) of labour in warm outdoor environments. Whole-day shifts with varying workloads were simulated using as input meteorological records for the hottest month from four cities with prevailing hot (Dallas, New Delhi) or warm-humid conditions (Managua, Osaka), respectively. In addition, we considered the effects of adaptive strategies like shielding against solar radiation and different work-rest schedules assuming an acclimated person wearing light work clothes (0.6 clo). We assessed WA according to Wet Bulb Globe Temperature (WBGT) by means of an empirical relation of worker performance from field studies (Hothaps), and as allowed work hours using safety threshold limits proposed by the corresponding standards. Using the physiological models Predicted Heat Strain (PHS) and Universal Thermal Climate Index (UTCI)-Fiala, we calculated WA as the percentage of working hours with body core temperature and cumulated sweat loss below standard limits (38 °C and 7.5% of body weight, respectively) recommended by ISO 7933 and below conservative (38 °C; 3%) and liberal (38.2 °C; 7.5%) limits in comparison. ANOVA results showed that the different metrics, workload, time of day and climate type determined the largest part of WA variance. WBGT-based metrics were highly correlated and indicated slightly more constrained WA for moderate workload, but were less restrictive with high workload and for afternoon work hours compared to PHS and UTCI-Fiala. Though PHS showed unrealistic dynamic responses to rest from work compared to UTCI-Fiala, differences in WA assessed by the physiological models largely depended on the applied limit criteria. In conclusion, our study showed that the choice of the heat stress assessment metric impacts notably on the estimated WA. Whereas PHS and UTCI-Fiala can account for cumulative physiological strain imposed by extended work hours when working heavily under high heat stress, the current WBGT standards do not include this. Advanced thermophysiological models might help developing alternatives, where not only modelling details but also the choice of physiological limit criteria will require attention. There is also an urgent need for suitable empirical data relating workplace heat exposure to workability. [ABSTRACT FROM AUTHOR]

The aim of the study was to compare the patterns of development of macrophytes and macroinvertebrates in different types of reference mountain rivers. The study is based on reference river sites surveyed throughout the mountains in Poland and Slovakia in two European ecoregions (9—Central Highlands, 10—The Carpathians). A wide range of environmental variables were estimated, including water chemistry, hydromorphology, geology, and the spatial factor. Based on the Jaccard index, macrophyte and macroinvertebrate variation was confirmed between four mountain and upland river types. It was found that the biological diversification is mainly influenced by geological and associated chemical factors. In the case of macroinvertebrates, additionally, the importance of the spatial factor was revealed (difference between ecoregions). Finally, the habitat preferences of various taxa were identified. It was found that extreme mountain conditions can sometimes distort bioindicative response, as was detected in the case of macroinvertebrates in the highest mountain sites. We concluded that consideration of two groups of organisms enables more comprehensive and reliable monitoring than assessment based on a single group, especially when standard bioindicative methods can be distorted by extreme local conditions. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association between cyclin-dependent kinase inhibitor 2A (CDKN2A) and cyclin-dependent kinase inhibitor 2B (CDKN2B) methylation, and coronary heart disease (CHD), and to explore the interaction between methylation status and CHD clinical characteristics in Han Chinese patients. A total of 189 CHD (96 males, 93 females) and 190 well-matched non-CHD controls (96 males, 94 females) were recruited for the study. Methylation-specific polymerase chain reaction technology was used to examine gene promoter methylation status. Comparisons of methylation frequencies between CHD and non-CHD patients were carried out using the Chi-square test. Methylation levels of CDKN2A and CDKN2B genes were not found to be associated with the risk of CHD. However, the mean age of CDKN2A-hypermethylated participants was significantly lower than CDKN2A-unmethylated participants (58.73±5.88 vs. 62.62±5.36 years, adjusted P<0.001). Conversely, the mean age of CDKN2B-hypermethylated participants was significantly higher compared with CDKN2B-unmethylated participants (62.26±5.48 vs. 58.33±7.47 years, adjusted P=0.048). In addition, CDKN2B methylation frequencies were significantly increased in female participants compared with males (99.47 vs. 11.98%, P=0.032). In conclusion, the results indicated that CDKN2A and CDKN2B promoter methylation frequencies were significantly associated with age, and there was a gender dimorphism in CDKN2B methylation. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD) characterized by a chronic, progressive course with multiorgan involvement. In our study, clinical, biochemical, molecular findings, and response to enzyme replacement therapy (ERT) for at least 6 months were evaluated in 20 patients with MPS VI. Treatment effects on clinical findings such as liver and spleen sizes, cardiac and respiratory parameters, visual and auditory changes, joints' range of motions, endurance tests and changes in urinary glycosaminoglycan excretions, before and after ERT were analyzed. ERT caused increased physical endurance and decreased urinary dermatan sulfate/chondroitin sulfate ratios. Changes in growth parameters, cardiac, respiratory, visual, auditory findings, and joint mobility were not significant. All patients and parents reported out an increased quality of life, which were not correlated with clinical results. The most prevalent mutation was p.L321P, accounting for 58.8% of the mutant alleles and two novel mutations (p.G79E and p.E390 K) were found. ERT was a safe but expensive treatment for MPS VI, with mild benefits in severely affected patients. Early treatment with ERT is mandatory before many organs and systems are involved. [ABSTRACT FROM AUTHOR]

Despite present diversity of graphene production methods there is still a high demand for improvement of the existing production schemes or development of new. Here a method is reviewed to produce graphene employing aromatic self-assembled monolayers (SAMs) as molecular precursors. This method is based on electron irradiation induced crosslinking of aromatic SAMs resulting in their conversion into carbon nanomembranes (CNMs) with high thermal stability and subsequent pyrolysis of CNMs into graphene in vacuum or in the inert atmosphere. Depending on the production conditions, such as chemical structure of molecular precursors, irradiation and annealing parameters, various properties of the produced graphene sheets including shape, crystallinity, thickness, optical properties and electric transport can be adjusted. The assembly of CNM/graphene van der Waals heterostructures opens a flexible route to non-destructive chemical functionalization of graphene for a variety of applications in electronic and photonic devices. [ABSTRACT FROM AUTHOR]

In humans, most fatalities from slaughterer's guns are suicides committed by persons familiar with stunning devices. The great majority of cases accounts for shots to the head, especially the frontal region. Only a small number of two subsequent cranial shots from captive-bolt humane killers have been reported up to now. In the case presented by the authors, a suicide by simultaneous shots to the head fired from two different makes of captive-bolt guns (one of them having two separate outlets for the combustion gases in the muzzle plane, the other type having no additional openings) is described for the first time. One of the shooting devices remained in firm contact with the left hand and produced patterned staining from rust corresponding to the surface relief of the gun. The medicolegal and criminalistic aspects of this unique case are discussed with reference to the pertinent literature. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether using the Tree flowchart obviates unnecessary magnetic resonance imaging (MRI)-guided biopsies in breast lesions only visible on MRI.Methods: This retrospective IRB-approved study evaluated consecutive suspicious (BI-RADS 4) breast lesions only visible on MRI that were referred to our institution for MRI-guided biopsy. All lesions were evaluated according to the Tree flowchart for breast MRI by experienced readers. The Tree flowchart is a decision rule that assigns levels of suspicion to specific combinations of diagnostic criteria. Receiver operating characteristic (ROC) curve analysis was used to evaluate diagnostic accuracy. To assess reproducibility by kappa statistics, a second reader rated a subset of 82 patients.Results: There were 454 patients with 469 histopathologically verified lesions included (98 malignant, 371 benign lesions). The area under the curve (AUC) of the Tree flowchart was 0.873 (95% CI: 0.839-0.901). The inter-reader agreement was almost perfect (kappa: 0.944; 95% CI 0.889-0.998). ROC analysis revealed exclusively benign lesions if the Tree node was ≤2, potentially avoiding unnecessary biopsies in 103 cases (27.8%).Conclusions: Using the Tree flowchart in breast lesions only visible on MRI, more than 25% of biopsies could be avoided without missing any breast cancer.Key Points: • The Tree flowchart may obviate >25% of unnecessary MRI-guided breast biopsies. • This decrease in MRI-guided biopsies does not cause any false-negative cases. • The Tree flowchart predicts 30.6% of malignancies with >98% specificity. • The Tree's high specificity aids in decision-making after benign biopsy results. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to assess the effectiveness of magnetic resonance imaging (MRI)-guided vacuum-assisted breast biopsy (VABB), evaluate and compare the characteristics and histopathologic findings of lesions, and overview the follow-up results of benign lesions.Methods: MRI findings and histopathologic results of breast lesions biopsied by MRI-guided VABB between 2013 and 2016 were retrospectively analyzed. MRI findings closely related with malignancy were investigated in particular. Follow-up results of benign lesions were evaluated.Results: MRI-guided VABB was applied to 116 lesions of 112 women. Of the lesions, 75 (65%) were benign, while 41 (35%) were malignant. Segmental (94%), clustered (89%), and clustered ring (67%) non-mass-like enhancement patterns were found to be more related with malignancy. False-negative rate of MRI-guided VABB was 12%, underestimation rate was 21%. One of the 54 followed-up benign lesions had a malignant result.Conclusion: MRI-guided VABB is a reliable method for the diagnosis of breast lesions that are positive only on MRI. Follow-up results show that cancer detection rate is low for radio-pathologically concordant lesions. Further multicenter studies with larger patient population are needed to elucidate these results. [ABSTRACT FROM AUTHOR]

Accumulating evidence from mainly uncontrolled clinical studies with various types of ablation catheters have shown that renal denervation (RDN) can be applied safely and is effective in lowering blood pressure (BP) in patients with treatment-resistant hypertension. Sustained BP lowering has been documented up to 3 years. Furthermore, RDN has been associated with regression of target organ damage, such as left ventricular hypertrophy, arterial stiffness, and others. Several studies indicate potential benefit in other common clinical conditions associated with increased sympathetic tone including chronic kidney disease and heart failure. However, the recently published Symplicity HTN-3 study, the largest and most rigorously designed sham-controlled clinical trial, while confirming the safety of the procedure, failed to demonstrate a BP lowering effect beyond that of a sham procedure in patients with resistant hypertension. Efforts to unravel the reasons for the discrepant results from Symplicity HTN-3 have focused on a range of potential confounders including anatomical and procedural aspects. Indeed, data from post-hoc analyses indicate that sufficient RDN may not have been achieved in the majority of patients in Symplicity HTN-3. Furthermore, recent evidence from human postmortem and functional animal studies revealed new insights into the anatomical distribution of renal nerves and their accessibility by intravascular approaches. Initial results from recent clinical trials integrating these important findings indeed seem to confirm that RDN remains a viable option for the treatment of hypertension. Thorough further investigations will be key to determine the true potential of RDN in clinical conditions characterized by increased sympathetic drive. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI)-guided interventions, including biopsies and wire localizations, are fundamental to any breast imaging practice due to the high sensitivity but limited specificity of breast MRI. The basic steps of MRI-guided biopsies are similar regardless of the vendor or platform, and technical considerations include approach planning, patient preparation and positioning, lesion targeting, and directional sampling using a vacuum-assisted biopsy technique. Unique challenges related to MRI-guided biopsies include vanishing lesions due to contrast washout, obscuration of the biopsy site due to susceptibility artifacts, and limited access to posteromedial lesions. A careful approach to planning, patient positioning, and lesion targeting will maximize the chances for a successful biopsy. Due to overlapping imaging features between benign and malignant lesions, radiologic-pathologic concordance is difficult and essential for further patient management.Level Of Evidence: 5 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:631-645. [ABSTRACT FROM AUTHOR]

Extensive investigations have revealed that renal sympathetic nerves regulate renin secretion, tubular fluid reabsorption and renal haemodynamics which can impact on cardiovascular homoeostasis normally and in pathophysiological states. The significance of the renal afferent innervation and its role in determining the autonomic control of the cardiovascular system is uncertain. The transduction pathways at the renal afferent nerves have been shown to require pro-inflammatory mediators and TRPV1 channels. Reno-renal reflexes have been described, both inhibitory and excitatory, demonstrating that a neural link exists between kidneys and may determine the distribution of excretory and haemodynamic function between the two kidneys. The impact of renal afferent nerve activity on basal and reflex regulation of global sympathetic drive remains opaque. There is clinical and experimental evidence that in states of chronic kidney disease and renal injury, there is infiltration of T-helper cells with a sympatho-excitation and blunting of the high- and low-pressure baroreceptor reflexes regulating renal sympathetic nerve activity. The baroreceptor deficits are renal nerve-dependent as the dysregulation can be relieved by renal denervation. There is also experimental evidence that in obese states, there is a sympatho-excitation and disrupted baroreflex regulation of renal sympathetic nerve activity which is mediated by the renal innervation. This body of information provides an important basis for directing greater attention to the role of renal injury/inflammation causing an inappropriate activation of the renal afferent nerves as an important initiator of aberrant autonomic cardiovascular control. [ABSTRACT FROM AUTHOR]

Background: Cardiac dysfunction is a severe complication of diabetes, with no effective treatment. Currently, bariatric surgery is more and more widely used to attenuate diabetes-associated diseases. The mechanism is not clear. Endoplasmic reticulum (ER) stress-dependent apoptosis has been observed in the progression of diabetic myocardium damage. Therefore, this research was designed to investigate the effects of different bariatric procedures on cardiac dysfunction via ER stress-induced cardiomyocyte apoptosis pathway in a diabetic rat model. Methods: Duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham surgery were performed in diabetic rats. Echocardiographic examination, H&E staining, Masson staining, and TUNEL staining were performed to measure the diabetes-caused heart damages. ER stress-associated signaling molecules like glucose-regulated protein 78 (GRP78), protein kinase RNA (PKR)-like ER protein kinase (PERK), p-PERK, inositol-requiring enzyme 1ɑ (IRE1ɑ), p-IRE1ɑ, activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), and caspase 12 were measured and compared among DJB group, SG group, and sham group. Results: Compared with sham group, DJB and SG groups both had significantly lower GRP78, PERK, p-PERK, CHOP, and caspase 12, though there was no statistical change on IRE1ɑ, p-IRE1ɑ, and ATF6. DJB and SG groups also showed improved heart function and lower cardiomyocyte apoptosis in diabetic rats. Conclusion: DJB and SG ameliorated cardiac dysfunction by inhibiting PERK-mediated pathway. And no difference was observed on the effects of DJB and SG on ER stress-dependent myocardium damage in diabetic rats. [ABSTRACT FROM AUTHOR]

Bryophytes play an important role in headwater stream ecosystems sensitive to human pressures. The high number of bryophyte species listed as threatened in Europe suggests that further efforts to conserve fluvial bryophyte diversity are needed. Investigations of the spatial ecology of bryophyte diversity should help identifying priority areas for conservation of fluvial bryophytes and their habitats., Seasonal temperate headwater streams were sampled at their southern edge distribution in Portugal, within and outside protected areas, at two spatial scales: stream segments and microhabitats. The environmental variables best explaining richness and diversity patterns, as well as the number of threatened species, were identified by partial least square regression. The selection of the best sites for conservation was achieved through the development of a new Index of Fluvial Bryological and Hydrogeomorphological Signature ( IFBHS)., At the stream segment scale, bryophyte community structure was highly influenced by hydrogeomorphological variables, in particular by hydrological features. At the microhabitat scale, high current velocity constrained bryophyte richness and diversity. The prioritised sites identified through the application of the IFBHS exhibited exceptional bryological richness, high levels of endemism and red-listed species, as well as unique fluvial microhabitats., Hydrological regime was identified as a major environmental driver of bryophyte community structure in seasonal headwater streams of southern temperate Europe, and this is of particular concern given projected scenarios of climate change and human-induced flow regime alterations. Prioritised stream segments for fluvial bryophyte and habitat conservation were not only located within protected areas, reinforcing the need to enhance the effectiveness of Natura 2000 Network and national protection areas. [ABSTRACT FROM AUTHOR]

Uncontrolled charging of electric vehicles (EVs) is expected to cause problems for power distribution networks as existing vehicles are continually being replaced by electric. Therefore, smart charging algorithms that prevent such problems will become necessary as uptake of EVs increases and they become more popular. Smart EV charging is not only useful to provide the necessary charge (energy) required by the user but may also be used to support the grid and protect battery health, which is investigated in this study. Factors that affect battery life are quantified and their impact on battery degradation and ability (of EV) to support the grid are analysed. Charging regimes that can meet the driver needs, provide grid support and protect the state of health of the battery are proposed in this study. The analysis presented demonstrates that smart charging that involves charging before departure, less frequent charging and limited vehicle‐to‐grid can prolong battery life compared with providing the same EV charge in an uncontrolled way. Thus, grid power is supported and battery life is protected by the proposed smart charging regimes. [ABSTRACT FROM AUTHOR]

The distribution of 14 rare earth elements, Th and U was studied in streams of the study area at 21 sites. Aquatic mosses are known to accumulate even metabolically nonessential or toxic metals in concentrations much higher than their aqueous environment due to their unique morphology and physiology. Thus, the capacity of metal amplification in four aquatic mosses ( Fontinalis squamosa, Brachythecium rivulare, Platyhypnidium riparioides and Thamnobryum alopecurum) was also evaluated as a potential bioindicator/biomonitoring tool. Thirteen REEs (0.001-2.81 μg L) and U were detected in the stream water. Mean content of lighter rare earth elements (LREEs) was higher than that of heavier rare earth elements (HREEs). Fourteen REEs and two actinides were detected in moss samples, including Yb and Th which were below detection level in water samples. LREE uptake (0.17-12.2 mg kg) was greater than HREE uptake (0.02-0.78 mg kg) in all mosses. Uptake of LREEs was observed in the order: B. rivulare > T. alopecurum > F. squamosa > P. riparioides and that of HREEs in the order: T. alopecurum > B. rivulare > F. squamosa > P. riparioides. Mean U content (0.68-1.62 mg kg) in the mosses was found in the order: B. rivulare > F. squamosa > T. alopecurum > P. riparioides. Th content ranged from 0.4 to 2.36 mg kg in the order: B. rivulare > T. alopecurum > P. riparioides > F. squamosa. One-way ANOVA indicated a statistically significant difference ( P ≤ 0.01) in mean concentrations of all elements (individually) in moss samples except for U. Highest bioconcentration factors of six REEs each were observed in B. rivulare (La, Ce, Sm, Eu, Tb and Dy) and T. alopecurum (Nd, Gd, Ho, Er, Tm and Lu). The highest BCFs for Pr and U were obtained in F. squamosa and P. riparioides, respectively. These species hold promise for biomonitoring studies in the future. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to perform a pilot evaluation of an integrated molecular breast imaging/ultrasound ( MBI/ US) system designed to enable, in real-time, the registration of US to MBI and diagnostic evaluation of breast lesions detected on MBI. Methods The MBI/ US system was constructed by modifying an existing dual-head cadmium zinc telluride ( CZT)-based MBI gamma camera. The upper MBI detector head was replaced with a mesh panel, which allowed an ultrasound probe to access the breast. An optical tracking system was used to monitor the location of the ultrasound transducer, referenced to the MBI detector. The lesion depth at which ultrasound was targeted was estimated from analysis of previously acquired dual-head MBI datasets. A software tool was developed to project the US field of view onto the current MBI image. Correlation of lesion location between both modalities with real-time MBI/ US scanning was confirmed in a breast phantom model and assessed in 12 patients with a breast lesion detected on MBI. Results Combined MBI/ US scanning allowed for registration of lesions detected on US and MBI as validated in phantom experiments. In patient studies, successful registration was achieved in 8 of 12 (67%) patients, with complete registration achieved in seven and partial registration achieved in one patient. In 4 of 12 (37%) patients, lesion registration was not achieved, partially attributed to uncertainty in lesion depth estimates from MBI. Conclusion The MBI/ US system enabled successful registration of US to MBI in over half of patients studied in this pilot evaluation. Future studies are needed to determine if real-time, registered US imaging of MBI-detected lesions may obviate the need to proceed to more expensive procedures such as contrast-enhanced breast MRI for diagnostic workup or biopsy of MBI findings. [ABSTRACT FROM AUTHOR]

Background: Amikacin is an aminoglycoside commonly used in intensive care units for the treatment of patients with life-threatening Gram-negative infections. Although aminoglycosides are extensively used, the accurate determination of their optimal dosage is complicated by marked intra- and interindividual variability in intensive care unit patients. Amikacin pharmacokinetics have been described in numerous studies over the past 25 years.Objective: This review presents a synthesis of the population pharmacokinetic models for amikacin described in critically ill patients. The objective was to determine whether there was a consensus on a structural model and which covariates had been identified.Methods: A literature search was conducted from the PubMed database, from its inception up until December 2015, using the following terms: 'amikacin', 'pharmacokinetic(s)', 'population', 'model(ling)' and 'nonlinear mixed effect'. Articles were excluded if they were not pertinent. The reference lists of all selected articles were also evaluated.Results: Ten articles were included in this review: pharmacokinetics of amikacin were described by a one-compartment or a two-compartment model. Various covariates were tested, but only two (creatinine clearance and total body weight) were included in almost all of the described models. After inclusion of these covariates, the interindividual variability (range) in clearance and the volume of distribution were 44.4 % (28.2-69.4 %) and 31.3 % (8.1-44.7 %), respectively. The residual variability (range) was around 21.0 % (9.0-31.0 %), using a proportional model, and for a combined model (proportional/additive), the median (range) values were 0.615 mg/L (0.2-1.03 mg/L) and 29.2 % (26.8-31.6 %).Conclusion: This review highlights the different population pharmacokinetic models for amikacin developed in critically ill patients over the past decades and proposes relevant information for clinicians and researchers. To optimize amikacin dosage, this review points out the relevant covariates according to the target population. In a population of critically ill patients, dose optimization mainly depends on creatinine clearance and total body weight. New pharmacokinetic population studies could be considered, with new covariates of interest to be tested in model building and to further explain variability. Another future perspective could be external evaluation of previously published models. [ABSTRACT FROM AUTHOR]

Ease of design, relatively low cost and a multitude of gene-altering capabilities have all led to the adoption of the sophisticated and yet simple gene editing system: clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). The CRISPR/Cas9 system holds promise for the correction of deleterious mutations by taking advantage of the homology directed repair pathway and by supplying a correction template to the affected patient's cells. Currently, this technique is being applied in vitro in human-induced pluripotent stem cells (iPSCs) to correct a variety of severe genetic diseases, but has not as of yet been used in iPSCs derived from patients affected with a lysosomal storage disease (LSD). If adopted into clinical practice, corrected iPSCs derived from cells that originate from the patient themselves could be used for therapeutic amelioration of LSD symptoms without the risks associated with allogeneic stem cell transplantation. CRISPR/Cas9 editing in a patient's cells would overcome the costly, lifelong process associated with currently available treatment methods, including enzyme replacement and substrate reduction therapies. In this review, the overall utility of the CRISPR/Cas9 gene editing technique for treatment of genetic diseases, the potential for the treatment of LSDs and methods currently employed to increase the efficiency of this re-engineered biological system will be discussed. [ABSTRACT FROM AUTHOR]

Both male/female patients with Fabry disease (FD) may receive enzyme replacement therapy (ERT). Previously published analyses of the Fabry Outcome Survey (FOS; Shire-sponsored) database suggested gender differences in timing of ERT initiation. We assessed alignment of criteria for ERT initiation in the Spanish adult population included in FOS with recommendations of a Spanish national consensus. This retrospective analysis examined baseline clinical data of 88 adults (49 females) enrolled in the FOS database up to August 2014. Thirty-five (39.8%) patients were not receiving ERT: five (12.8%) males and 30 (61.2%) females. Baseline disease severity on the FOS-derived Mainz Severity Score Index was lower in untreated males (median (interquartile range), 0.0 (0.0-1.0)) than treated males (TM; 15.0 (7.5-26.5)), and was similar in untreated and treated females. The percentage of untreated females with at least one criterion for treatment initiation was 76.7% versus 100.0% of treated females (p = 0.0340) and 97.1% (p = 0.0210) of TM. In discordance with Spanish consensus recommendations, a substantial number of females with evidence of FD who might benefit from ERT have not yet initiated treatment. These results suggest unequal gender perceptions with respect to ERT initiation in Spain. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare three different biopsy devices on false-negative and underestimation rates in MR-guided, vacuum-assisted breast biopsy (VABB) of MRI-only lesions.Methods: This retrospective, single-center study was IRB-approved. Informed consent was waived. 467 consecutive patients underwent 487 MR-guided VABB using three different 8-10-gauge-VABB devices (Atec-9-gauge,A; Mammotome-8-gauge,M; Vacora-10-gauge,V). VABB data (lesion-type, size, biopsy device, histopathology) were compared to final diagnosis (surgery, n = 210 and follow-up, n = 277). Chi-square, and Kruskal-Wallis tests were applied. P values < 0.05 were considered significant.Results: Final diagnosis was malignant in 104 (21.4 %), high risk in 64 (13.1 %) and benign in 319 (65.5 %) cases. Eleven of 328 (3.4 %) benign-rated lesions were false-negative (1/95, 1.1 %, A; 2/73, 2.7 %, M; 8/160 5.0 % V; P = 0.095). Eleven high-risk (11/77, 14.3 %) lesions proved to be malignant (3/26, 11.5 % A; 4/12, 33.3 % M; 4/39, 10.3 % V; P = 0.228). Five of 34 (14.7 %) DCIS were upgraded to invasive cancer (2/15, 13.3 %, A; 1/6, 16.6 % M; 2/13, 15.3 %, V; P = 0.977). Lesion size (P = 0.05) and type (mass vs. non-mass, P = 0.107) did not differ significantly.Conclusion: MR-guided VABB is an accurate method for diagnosis of MRI-only lesions. No significant differences on false-negative and underestimation rates were observed between three different biopsy devices.Key Points: • MR-guided VABB is an accurate procedure for the diagnosis of MRI-only lesions. • Similar false-negative and underestimation rates allow all three different MR-guided VABB devices for clinical application. • High-risk lesions should undergo surgery due to a substantial underestimation rate. • Agreement between MR-guided VABB and final diagnosis (benign/malignant) was 95.5% (465/487). [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effect of spray-dried porcine plasma ( SDPP) in broiler chickens under Salmonella sofia disease challenge. The experiment comprised five starter diets: positive control (no supplement), diet supplemented with in-feed antibiotics ( IFA; salinomycin 0.05% + zinc bacitracin 0.033%) and diets supplemented with SDPP at 10 or 20 g/kg diet. All four of these groups were challenged with S. sofia, while a fifth group was unchallenged and used as the negative control. The experimental diets were fed to 14 days; then, the birds were switched to commercial-type grower and finisher diets. Oral inoculation of the challenged groups with S. sofia occurred on day 8, 10 and 12. Body weight was significantly higher in the birds fed diets containing IFA and SDPP than in the challenged control group, but it was only significant in starter and grower phases. In general, there was an improvement in the weights of the immune-related organs, but it was only significant for the weight of the bursa of SDPP-fed birds at 13 days. At day 13, blood potassium content was lower and the concentrations of IgG and IgM tended to be lower in the birds fed on low- SDPP starter diets than those of the other groups. There were significant differences in the concentration of lactic acid in the ileum and acetic acid, formic acid, butyric acid and propionic acid in the caeca. Inclusion of SDPP to the starter diets of broiler chicks had positive effects on broiler performance, immunity and gut health during exposure to highly pathogenic conditions. [ABSTRACT FROM AUTHOR]

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The purpose of this study is to obtain a consensus for the therapy of B3 lesions. The first International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions) including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumors (PT), and radial scars (RS) took place in January 2016 in Zurich, Switzerland organized by the International Breast Ultrasound School and the Swiss Minimally Invasive Breast Biopsy group-a subgroup of the Swiss Society of Senology. Consensus recommendations for the management and follow-up surveillance of these B3 lesions were developed and areas of research priorities were identified. The consensus recommendation for FEA, LN, PL, and RS diagnosed on core needle biopsy or vacuum-assisted biopsy (VAB) is to therapeutically excise the lesion seen on imaging by VAB and no longer by open surgery, with follow-up surveillance imaging for 5 years. The consensus recommendation for ADH and PT is, with some exceptions, therapeutic first-line open surgical excision. Minimally invasive management of selected B3 lesions with therapeutic VAB is acceptable as an alternative to first-line surgical excision. [ABSTRACT FROM AUTHOR]

The mucopolysaccharidoses (MPS) comprise a heterogeneous family of rare, genetic lysosomal storage disorders that result in severe morbidity and reduced life expectancy. Emerging treatments for several of these disorders have triggered the search for clinically relevant biomarkers and clinical markers associated with treatment efficacy in populations and individuals. However, biomedical measures do not tell the whole story when characterizing a complex chronic disorder such as MPS. Health-related quality of life (HRQoL) tools that utilize patient reported outcomes to address patient parameters such as symptoms (pain, fatigue, psychological health), functioning (activity and limitations), or quality of life, have been used to supplement traditional biomedical endpoints. Many of these HRQoL tools have demonstrated that quality of life is negatively impacted in patients with MPS. There is both the opportunity and need to formally standardize and validate HRQoL tools for the different MPS disorders. [ABSTRACT FROM AUTHOR]

Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of GMS Journal for Medical Education is the property of German Medical Science Publishing House gGmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: At the University of Leipzig, the requirements of the Licensing Regulations for Doctors (Approbationsordnungfür Ärzte) for the practical training of communication skills are actively implemented by a two- semester communication course. During this course, student tutors impart the basics of interpersonal as well as selected aspects of doctor- patient communication using interactive training methods. This article reports on the effect the training has on the self-assessed communication skills of the medicine students. Methods: The students' self-perceived communication skills were assessed, both at the beginning and after the completion of the first and second course semesters using questionnaires related to the course's learning goals. Pre-post comparisons were then carried out. 142 students (of 163 students in total) participated in the survey at the start of the course, of which 117 completed the T2-questionnaire at the end of the first course semester. Only the 84 students who also completed the questionnaires in the second course semester were included in the statistical analysis. These responses were analysed using both descriptive and inferential statistics. Results: The comparison of the self-assessments between the four measurement points showed that statistically significant learning progress for all assessed communication skills had taken place from the point of view of the students. The largest changes between measurements, and therefore the greatest learning progress, could be seen in knowledge related skills. Conclusion: From the students' point of view the communication training contributes significantly to the acquisition of communication skills. The results suggest thatthis "hands-on" course concept is suited to successfully enhance the students' communication skills. The course concept should therefore be retained for both the course in its current form as well as for any extension of the course into the clinical part of medical school. However, further assessments on the exam results and longterm effects should take place. [ABSTRACT FROM AUTHOR]

Microbial endoliths, which inhabit interior pores of rocks, skeletons and coral, are ubiquitous in terrestrial and marine environments. In this study, various colored layers stratified the endolithic environment within the skeleton of Isopora palifera; however, there was a distinct green-pigmented layer in the skeleton (beneath the living coral tissue). To characterize diversity of endolithic microorganisms, 16S ribosomal RNA gene amplicon pyrosequencing was used to investigate bacterial communities in the green layer of eight I. palifera coral colonies retrieved from two locations on Green Island, Taiwan. The dominant bacterial group in the green layer belonged to the bacterial phylum Chlorobi, green sulfur bacteria capable of anoxygenic photosynthesis and nitrogen fixation. Specifically, bacteria of the genus Prosthecochloris were dominant in this green layer. To our knowledge, this is the first study to provide a detailed profile of endolithic bacteria in coral and to determine the prevalence of Prosthecochloris in the green layer. Based on our findings, we infer that these bacteria may have an important functional role in the coral holobiont in the nutrient-limited coral reef ecosystem. [ABSTRACT FROM AUTHOR]

Implant constructs supporting angiogenesis are favorable for treating critically-sized bone defects, as ingrowth of capillaries towards the center of large defects is often insufficient. Consequently, the insufficient nutritional supply of these regions leads to impaired bone healing. Implants with specially designed angiogenic supporting geometry and functionalized with proangiogenic cytokines can enhance angiogenesis. In this study, Vascular Endothelial Growth Factor (VEGF) and High Mobility Group Box 1 (HMGB1) were used for incorporation into poly-ε-caprolactone (PCL)-coated porous titanium implants. Bioactivity of released factors and influence on angiogenesis of functionalized implants were evaluated using a migration assay and angiogenesis assays. Both implants released angiogenic factors, inducing migration of endothelial cells. Also, VEGF-functionalized PCL-coated titanium implants enhanced angiogenesis in vitro. Both factors were rapidly released in high doses from the implant coating during the first 72 h. [ABSTRACT FROM AUTHOR]

Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.

Maroteaux-Lamy syndrome is a very rare multisystem disorder. Cardiac valve surgery is common in these patients who present a unique set of perioperative and intraoperative challenges to the surgeon and treating team. We describe successful mitral valve replacement using an inverted aortic prosthesis in a 29-year-old lady with Maroteaux-Lamy syndrome, with a good result at 10 months. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Oncology is the property of Chinese Journal of Oncology / Zhonghua Zhongliu Zazhi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)