We compared and contrasted fish assemblage data sampled by baited remote underwater stereo-video systems (stereo-BRUVs) and stereo-video remotely operated vehicles (stereo-ROVs) from subsea ...pipelines, reef and soft sediment habitats. Stereo-BRUVs sampled greater fish diversity across all three habitats, with the stereo-ROV sampling ~46% of the same species on pipeline and reef habitats. Larger differences existed in soft sediment habitats, with stereo-BRUVs recording ~65% more species than the stereo-ROV, the majority of which were generalist carnivores. These differences were likely due to the bait used with stereo-BRUVs attracting fish from a large and unknown area. Fish may have also avoided the moving stereo-ROV, an effect possibly magnified in open soft sediment habitats. As a result of these biases, we recommend stereo-ROVs for assessing fish communities on pipelines due to their ability to capture fish in-situ and within a defined sampling area, but caution is needed over soft sediment habitats for ecological comparisons.
•Stereo-BRUVs and Stereo-ROV sampled different compositions of fish on and off the pipeline.•Stereo-ROV may under-sample fish in open sandy habitats.•Stereo-BRUVs may over-sample fine-scale habitat associations due to bait attraction.•Stereo-ROV samples fish-habitat associations in greater detail.•Stereo-ROV is a more suitable tool for sampling fish on pipeline and fine-scale structures.
Objectives This study sought to evaluate long-term in vivo functionality, host cell repopulation, and remodeling of “off-the-shelf” tissue engineered transcatheter homologous heart valves. Background ...Transcatheter valve implantation has emerged as a valid alternative to conventional surgery, in particular for elderly high-risk patients. However, currently used bioprosthetic transcatheter valves are prone to progressive dysfunctional degeneration, limiting their use in younger patients. To overcome these limitations, the concept of tissue engineered heart valves with self-repair capacity has been introduced as next-generation technology. Methods In vivo functionality, host cell repopulation, and matrix remodeling of homologous transcatheter tissue-engineered heart valves (TEHVs) was evaluated up to 24 weeks as pulmonary valve replacements (transapical access) in sheep (n = 12). As a control, tissue composition and structure were analyzed in identical not implanted TEHVs (n = 5). Results Transcatheter implantation was successful in all animals. Valve functionality was excellent displaying sufficient leaflet motion and coaptation with only minor paravalvular leakage in some animals. Mild central regurgitation was detected after 8 weeks, increasing to moderate after 24 weeks, correlating to a compromised leaflet coaptation. Mean and peak transvalvular pressure gradients were 4.4 ± 1.6 mm Hg and 9.7 ± 3.0 mm Hg, respectively. Significant matrix remodeling was observed in the entire valve and corresponded with the rate of host cell repopulation. Conclusions For the first time, the feasibility and long-term functionality of transcatheter-based homologous off-the-shelf tissue engineered heart valves are demonstrated in a relevant pre-clinical model. Such engineered heart valves may represent an interesting alternative to current prostheses because of their rapid cellular repopulation, tissue remodeling, and therewith self-repair capacity. The concept of homologous off-the-shelf tissue engineered heart valves may therefore substantially simplify previous tissue engineering concepts toward clinical translation.
Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral ...intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds 4 weeks. We aimed to develop and externally validate a prediction model to identify patients who need TF ≥ 4 weeks and would benefit from prophylactic gastrostomy insertion.
A retrospective multicenter cohort study was performed in four tertiary head and neck cancer centers in the Netherlands. The prediction model was developed using data from University Medical Center Utrecht and the Netherlands Cancer Institute and externally validated using data from Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF dependency ≥4 weeks initiated during CRT/BRT or within 30 days after CRT/BRT completion. Potential predictors were extracted from electronic health records and radiotherapy dose–volume parameters were calculated.
The developmental and validation cohort included 409 and 334 patients respectively. Multivariable analysis showed predictive value for pretreatment weight change, texture modified diet at baseline, ECOG performance status, tumor site, N classification, mean radiation dose to the contralateral parotid gland and oral cavity. The area under the receiver operating characteristics curve for this model was 0.73 and after external validation 0.62. Positive and negative predictive value for a risk of 90% or higher for TF dependency ≥4 weeks were 81.8% and 42.3% respectively.
We developed and externally validated a prediction model to estimate TF-dependency ≥4 weeks in LAHNSCC patients treated with CRT/BRT. This model can be used to guide personalized decision-making on prophylactic gastrostomy insertion in clinical practice.
Bone metastases are frequent in patients with non-small cell lung cancer (NSCLC). The receptor activator of Nuclear Factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is important in ...bone metastases development. Furthermore, epidermal growth factor receptor (EGFR) signaling promotes osteoclast formation and stimulation. The understanding of the biological mechanism of bone metastases development might have implications for treatment strategies. Therefore, we studied whether there is an association between EGFR, RANKL, RANK and OPG gene expression in the tumor and presence of bone metastases in patients with NSCLC.
From an updated multicenter study, including patients with
mutated (
+), Kirsten rat sarcoma
and
wildtype metastatic NSCLC, all patients with available formalin-fixed paraffin-embedded (FFPE) tumor samples were selected. Ribonucleic Acid (RNA) was isolated from these samples and gene expressions of EGFR, RANKL, OPG and RANKL were determined
quantitative Polymerase Chain Reaction (qPCR). Data on demographics, histology and molecular subtyping, sample origin, presence of bone metastasis, SREs and bone progression were collected. Primary endpoint was relation between EGFR, RANK, RANKL, OPG gene expression, RANKL: OPG ratio and bone metastases.
In 73/335 (32%
, 49%
, 19%
wildtype) samples from unique patients, gene expression analysis could be performed. Of these 73 patients, 46 (63%) had bone metastases at diagnosis or developed bone metastases during the disease course. No association was found between EGFR expression and presence of bone metastases. Patients with bone metastases had a significantly higher RANKL expression and RANKL: OPG ratio compared to those without. An increased RANKL: OPG ratio resulted in a 1.65x increased risk to develop bone metastases, especially in the first 450 days after diagnosis of metastatic NSCLC.
Increased RANKL gene expression and RANKL: OPG ratio, but not EGFR expression, was associated with presence of bone metastases. Additionally, an increased RANKL: OPG gene ratio was associated with a higher incidence of bone metastases development.
Over the last 2 decades, it has become increasingly evident that incremental adaptation to global environmental challenges—particularly climate change—no longer suffices. To make matters worse, ...systemic problems such as social inequity and unsustainable use of resources prove to be persistent. These challenges call for, such is the rationale, significant and radical systemic changes that challenge incumbent structures. Remarkably, scholarship on sustainability transformations has only engaged with the role of power dynamics and shifts in a limited fashion. This paper responds to a need for methods that support the creation of imaginative transformation pathways while attending to the roles that power shifts play in transformations. To do this, we extended the “Seeds of Good Anthropocenes” approach, incorporating questions derived from scholarship on power into the methodology. Our ‘Disruptive Seeds’ approach focuses on niche practices that actively challenge unsustainable incumbent actors and institutions. We tested this novel approach in a series of participatory pilot workshops. Generally, the approach shows great potential as it facilitates explicit discussion about the way power shifts may unfold in transformations. It is a strong example of the value of mixing disciplinary perspectives to create new forms of scenario thinking—following the call for more integrated work on anticipatory governance that combines futures thinking with social and political science research into governance and power. Specifically, the questions about power shifts in transformations used in this paper to adapt the Seeds approach can also be used to adapt other future methods that similarly lack a focus on power shifts—for instance, explorative scenarios, classic back-casting approaches, and simulation gaming.
Empathy describes the ability to understand another person's feelings. Psychopathy is a disorder that is characterized by a lack of empathy. Therefore, empathy and psychopathy are interesting traits ...to investigate with respect to experiencing and observing pain. The present study aimed to investigate pain empathy and pain sensitivity by measuring event-related potentials (ERPs) extracted from the ongoing EEG in an interactive setup. Each participant fulfilled subsequently the role of "villain" and "victim". In addition, mode of control was modulated resulting in four different conditions; passive villain, active villain, active victim and passive victim. Response-, visual- and pain ERPs were compared between the four conditions. Furthermore, the role of psychopathic traits in these outcomes was investigated. Our findings suggested that people experience more conflict when hurting someone else than hurting themselves. Furthermore, our results indicated that self-controlled pain was experienced as more painful than uncontrolled pain. People that scored high on psychopathic traits seemed to process and experience pain differently. According to the results of the current study, social context, attention and personality traits seem to modulate pain processing and the empathic response to pain in self and others. The within-subject experimental design described here provides an excellent approach to further unravel the influence of social context and personality traits on social cognition.
Proper pain therapy requires adequate pain assessment. This study evaluated the reliability and validity of the Unesp-Botucatu horse acute pain scale (UHAPS), the Orthopedic Composite Pain Scale ...(CPS) and unidimensional scales in horses admitted for orthopedic and soft tissue surgery. Forty-two horses were assessed and videotaped before surgery, up to 4 hours postoperatively, up to 3 hours after analgesic treatment, and 24 hours postoperatively (168 video clips). After six evaluators viewing each edited video clip twice in random order at a 20-day interval, they chose whether analgesia would be indicated and applied the Simple Descriptive, Numeric and Visual Analog scales, CPS, and UHAPS. For all evaluators, intra-observer reliability of UHAPS and CPS ranged from 0.70 to 0.97. Reproducibility was variable among the evaluators and ranged from poor to very good for all scales. Principal component analysis showed a weak association among 50% and 62% of the UHAPS and CPS items, respectively. Criterion validity based on Spearman correlation among all scales was above 0.67. Internal consistency was minimally acceptable (0.51-0.64). Item-total correlation was acceptable (0.3-0.7) for 50% and 38% of UHAPS and CPS items, respectively. UHAPS and CPS were specific (90% and 79% respectively), but both were not sensitive (43 and 38%, respectively). Construct validity (responsiveness) was confirmed for all scales because pain scores increased after surgery. The cut-off point for rescue analgesia was greater than or equal to 5 and greater than or equal to 7 for the UHAPS and CPS, respectively. All scales presented adequate repeatability, criterion validity, and partial responsiveness. Both composite scales showed poor association among items, minimally acceptable internal consistency, and weak sensitivity, indicating that they are suboptimal instruments for assessing postoperative pain. Both composite scales require further refinement with the exclusion of redundant or needless items and reduction of their maximum score applied to each item or should be replaced by other tools.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an ...increased ToM ability to hyperattribute others' mental states (overmentalizing).
Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia.
In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample.
Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia.
The IL11 receptor (IL11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors, such as prostate cancer. However, its ...potential role in management of hematopoietic malignancies has not yet been determined. Here, we evaluated the IL11R as a candidate therapeutic target in human leukemia and lymphoma.
First, we show that the IL11R protein is expressed in a variety of human leukemia- and lymphoma-derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, whereas expression is absent from nonmalignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analogue with an apparent improved antileukemia cell profile.
These results indicate (i) that the IL11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases.
Precapillary pulmonary hypertension (pPH) affects left ventricular (LV) function by ventricular interdependence. Since LV ejection fraction (EF) is commonly preserved, LV dysfunction should be ...assessed with more sensitive techniques. Left atrial (LA) strain and estimation of LV intraventricular pressure gradients (IVPG) may be valuable in detecting subtle changes in LV mechanics; however, the value of these techniques in pPH is unknown. Therefore, the aim of our study is to evaluate LA strain and LV-IVPGs from cardiovascular magnetic resonance (CMR) cines in pPH patients.
In this cross-sectional study, 31 pPH patients and 22 healthy volunteers underwent CMR imaging. Feature-tracking LA strain was measured on four- and two-chamber cines. LV-IVPGs (from apex-base) are computed from a formulation using the myocardial movement and velocity of the reconstructed 3D-LV (derived from long-axis cines using feature-tracking). Systolic function, both LV EF and systolic ejection IVPG, was preserved in pPH patients. Compared to healthy volunteers, diastolic function was impaired in pPH patients, depicted by (i) lower LA reservoir (36 ± 7% vs. 26 ± 9%, P < 0.001) and conduit strain (26 ± 6% vs. 15 ± 8%, P < 0.001) and (ii) impaired diastolic suction (-9.1 ± 3.0 vs. ‒6.4 ± 4.4, P = 0.02) and E-wave decelerative IVPG (8.9 ± 2.6 vs. 5.7 ± 3.1, P < 0.001). Additionally, 11 pPH patients (35%) showed reversal of IVPG at systolic-diastolic transition compared to none of the healthy volunteers (P = 0.002).
pPH impacts LV function by altering diastolic function, demonstrated by an impairment of LA phasic function and LV-IVPG analysis. These parameters could therefore potentially be used as early markers for LV functional decline in pPH patients.