Notes

Bone injuries in neglected patients with weakening of bones within Belgium: a great InGef health-related insurance database investigation.
This paper investigates the asymptotic properties of estimators obtained from the so called CVA (canonical variate analysis) subspace algorithm proposed by Larimore (1983) in the case when the data is generated using a minimal state space system containing unit roots at the seasonal frequencies such that the yearly difference is a stationary vector autoregressive moving average (VARMA) process. The empirically most important special cases of such data generating processes are the I(1) case as well as the case of seasonally integrated quarterly or monthly data. However, increasingly also datasets with a higher sampling rate such as hourly, daily or weekly observations are available, for example for electricity consumption. In these cases the vector error correction representation (VECM) of the vector autoregressive (VAR) model is not very helpful as it demands the parameterization of one matrix per seasonal unit root. Even for weekly series this amounts to 52 matrices using yearly periodicity, for hourly data terly macroeconomic data. Further simulations show that the unit root tests are robust with respect to different distributions for the innovations as well as with respect to GARCH-type conditional heteroskedasticity. Moreover, an application to Kaggle data on hourly electricity consumption by different American providers demonstrates the usefulness of the method for applications. Therefore the CVA algorithm provides a very useful initial guess for subsequent quasi maximum likelihood estimation and also delivers relevant information on the cointegrating ranks at the different unit root frequencies. It is thus a useful tool for example in (but not limited to) automatic modeling applications where a large number of time series involving a substantial number of variables need to be modelled in parallel.Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis with a 5 year survival rate of less than 8%, and is predicted to become the second leading cause of cancer-related death by 2030. Alongside late detection, which impacts upon surgical treatment, PDAC tumours are challenging to treat due to their desmoplastic stroma and hypovascular nature, which limits the effectiveness of chemotherapy and radiotherapy. Pancreatic stellate cells (PSCs), which form a key part of this stroma, become activated in response to tumour development, entering into cross-talk with cancer cells to induce tumour cell proliferation and invasion, leading to metastatic spread. We and others have shown that Fibroblast Growth Factor Receptor (FGFR) signalling can play a critical role in the interactions between PDAC cells and the tumour microenvironment, but it is clear that the FGFR signalling pathway is not acting in isolation. Here we describe our current understanding of the mechanisms by which FGFR signalling contributes to PDAC progression, focusing on its interaction with other pathways in signalling networks and discussing the therapeutic approaches that are being developed to try and improve prognosis for this terrible disease.Unmanned Aerial Vehicles (UAVs, also known as drones) have become increasingly appealing with various applications and services over the past years. Drone-based remote sensing has shown its unique advantages in collecting ground-truth and real-time data due to their affordable costs and relative ease of operability. This paper presents a 3D placement scheme for multi-drone sensing/monitoring platforms, where a fleet of drones are sent for conducting a mission in a given area. It can range from environmental monitoring of forestry, survivors searching in a disaster zone to exploring remote regions such as deserts and mountains. The proposed drone placing algorithm covers the entire region without dead zones while minimizing the number of cooperating drones deployed. Naturally, drones have limited battery supplies which need to cover mechanical motions, message transmissions and data calculation. Consequently, the drone energy model is explicitly investigated and dynamic adjustments are deployed on drone locations. The proposed drone placement algorithm is 3D landscaping-aware and it takes the line-of-sight into account. The energy model considers inter-communications within drones. The algorithm not only minimizes the overall energy consumption, but also maximizes the whole drone team's lifetime in situations where no power recharging facilities are available in remote/rural areas. Simulations show the proposed placement scheme has significantly prolonged the lifetime of the drone fleet with the least number of drones deployed under various complex terrains.Inducing apoptosis is an effective treatment for cancer. Conventional cytotoxic anticancer agents induce apoptosis primarily through activation of tumor suppressor p53 by causing DNA damage and the resulting regulation of B-cell leukemia/lymphoma-2 (BCL-2) family proteins. Therefore, the effects of these agents are limited in cancers where p53 loss-of-function mutations are common, such as triple-negative breast cancer (TNBC). Here, we demonstrate that ultraviolet (UV) light-induced p53-independent transcriptional activation of NOXA, a proapoptotic factor in the BCL-2 family, results in apoptosis induction. This UV light-induced NOXA expression was triggered by extracellular signal-regulated kinase (ERK) activity. Moreover, we identified the specific UV light-inducible DNA element of the NOXA promoter and found that this sequence is responsible for transcription factor Krüppel-like factor 4 (KLF4)-mediated induction. In p53-mutated TNBC cells, inhibition of KLF4 by RNA interference reduced NOXA expression. Furthermore, treatment of TNBC cells with a KLF4-inducing small compound, APTO-253, resulted in the induction of NOXA expression and NOXA-mediated apoptosis. Therefore, our results help to clarify the molecular mechanism of DNA damage-induced apoptosis and provide support for a possible treatment method for p53-mutated cancers.The utilization of person-centered care is highlighted as essential for health promotion, yet implementation has been inconsistent and multiple issues remain. There is a dearth of applied research exploring the facets of successful implementation. In this paper, a person-centered wellbeing program spanning various groups is discussed, outlining the central principles that have allowed for successful outcomes. Ten years of pragmatic pre-post service evaluation have shown consistent improvement in measures of functional capacity and wellbeing. The method for this paper is a reflective exploration of the theory and practices that can explain the continual improvement the clinics have achieved over 10 years. Core principles relate to connecting with people, connecting through groups, and connecting with self. The operationalization and theoretical explanation of these principles is outlined. The discussion of these principles posits essential factors to prioritize to advance the implementation of person-centered care in health promotion for long-term conditions.Streptococcus mitis-oralis (S. read more mitis-oralis) infections are increasingly prevalent in specific populations, including neutropenic cancer and endocarditis patients. S. mitis-oralis strains have a propensity to evolve rapid, high-level and durable resistance to daptomycin (DAP-R) in vitro and in vivo, although the mechanism(s) involved remain incompletely defined. We examined mechanisms of DAP-R versus cross-resistance to cationic host defense peptides (HDPs), using an isogenic S. mitis-oralis strain-pair (i) DAP-susceptible (DAP-S) parental 351-WT (DAP MIC = 0.5 µg/mL), and its (ii) DAP-R variant 351-D10 (DAP MIC > 256 µg/mL). DAP binding was quantified by flow cytometry, in-parallel with temporal (1-4 h) killing by either DAP or comparative prototypic cationic HDPs (hNP-1; LL-37). Multicolor flow cytometry was used to determine kinetic cell responses associated with resistance or susceptibility to these molecules. While overall DAP binding was similar between strains, a significant subpopulation of 351-D10 cells hyper-accumulated DAP (>2-4-fold vs. 351-WT). Further, both DAP and hNP-1 induced cell membrane (CM) hyper-polarization in 351-WT, corresponding to significantly greater temporal DAP-killing (vs. 351-D10). No strain-specific differences in CM permeabilization, lipid turnover or regulated cell death were observed post-exposure to DAP, hNP-1 or LL-37. Thus, the adaptive energetics of the CM appear coupled to the outcomes of interactions of S. mitis-oralis with DAP and selected HDPs. In contrast, altered CM permeabilization, proposed as a major mechanism of action of both DAP and HDPs, did not differentiate DAP-S vs. DAP-R phenotypes in this S. mitis-oralis strain-pair.Most type 2 diabetes patients are treated in general practice and there is a need of developing and implementing efficient lifestyle interventions. eHealth interventions have shown to be effective in promoting a healthy lifestyle. The purpose of this study was to test the feasibility, including the identification of factors of importance, when offering digital lifestyle coaching to type 2 diabetes patients in general practice. We conducted a qualitative feasibility study with focus group interviews in four general practices. We identified two overall themes and four subthemes (1) the distribution of roles and lifestyle interventions in general practice (subthemes external and internal distribution of roles) and (2) the pros and cons for digital lifestyle interventions in general practice (subthemes access to real life data and change in daily routines). We conclude that for digital lifestyle coaching to be feasible in a general practice setting, it was of great importance that the general practitioners and practice nurses knew the role and content of the intervention. In general, there was a positive attitude in the general practice setting towards referring type 2 diabetes patients to digital lifestyle intervention if it was easy to refer the patients and if easily understandable and accessible feedback was implemented into the electronic health record. It was important that the digital lifestyle intervention was flexible and offered healthcare providers in general practice an opportunity to follow the type 2 diabetes patient closely.The vibrational spectrum of the Ala-Leu-Ala-Leu peptide in solution, computed from first-principles simulations, shows a prominent band in the amide I region that is assigned to stretching of carbonyl groups. Close inspection reveals combined but slightly different contributions by the three carbonyl groups of the peptide. The shift in their exact vibrational signature is in agreement with the different probabilities of these groups to form hydrogen bonds with the solvent. The central carbonyl group has a hydrogen bond probability intermediate to the other two groups due to interchanges between different hydrogen-bonded states. Analysis of the interaction energies of individual water molecules with that group shows that shifts in its frequency are directly related to the interactions with the water molecules in the first hydration shell. The interaction strength is well correlated with the hydrogen bond distance and hydrogen bond angle, though there is no perfect match, allowing geometrical criteria for hydrogen bonds to be used as long as the sampling is sufficient to consider averages.
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