Exploring the potential for groundwater-related ground deformation in Southern New South Wales, Australia.

Unsustainable groundwater extraction can lead to aquifer compaction, damages to infrastructure, changes of water accumulation in rivers and lakes and to a decrease of the aquifer's ability to store water for future generations. While this phenomenon is well identified across the globe, the potential for groundwater-related ground deformation is still largely unknown for most of the heavily exploited aquifers of Australia. This study fills that science gap by exploring signs of this phenomenon across a large region comprising seven of Australia's most intensively exploited aquifers, in the New South Wales Riverina region. To detect ground deformation, we processed 396 Sentinel-1 swaths acquired during 2015-2020 using a multitemporal spaceborne radar interferometry (InSAR), leading to the production of a near-continuous ground deformation maps covering ~280,000 km2. To explore potential groundwater-induced deformation hotspots, four criteria are used in a multiple-line of evidence approach: (1) the amplitude, shape, and extent of the InSAR ground displacement anomaly, (2) the spatial correspondence with groundwater extraction hotspots. (3) The correlations between InSAR deformation time series and change in head levels in 975 wells. Four areas are identified as potentially prone to inelastic, groundwater-related deformations, with average deformation rates ranging from -10 to -30 mm/yr, high rates of groundwater extraction, and ample critical head drops. Comparison of ground deformation and groundwater level time series also suggests potential for elastic deformation in some of these aquifers. This study will help water managers mitigating the groundwater-related ground deformation risk.

Control charts for measurement error models.

We consider a linear measurement error model (MEM) with AR(1) process in the state equation which is widely used in applied research. This MEM could be equivalently re-written as ARMA(1,1) process, where the MA(1) parameter is related to the variance of measurement errors. As the MA(1) parameter is of essential importance for these linear MEMs, it is of much relevance to provide instruments for online monitoring in order to detect its possible changes. In this paper we develop control charts for online detection of such changes, i.e., from AR(1) to ARMA(1,1) and vice versa, as soon as they occur. For this purpose, we elaborate on both cumulative sum (CUSUM) and exponentially weighted moving average (EWMA) control charts and investigate their performance in a Monte Carlo simulation study. The empirical illustration of our approach is conducted based on time series of daily realized volatilities.

New Approaches for Monitoring Image Data.

In this paper, we develop new techniques for monitoring image processes under a fairly general setting with spatially correlated pixels in the image. Monitoring and handling the pixels directly is infeasible due to an extremely high image resolution. To overcome this problem, we suggest control charts that are based on regions of interest. The regions of interest cover the original image which leads to a dimension reduction. Nevertheless, the data are still high-dimensional. We consider residual charts based on the generalized likelihood ratio approach. Existing control statistics typically depend on the inverse of the covariance matrix of the process, involving high computing times and frequently generating instable results in a high-dimensional setting. As a solution of this issue, we suggest two further control charts that can be regarded as modifications of the generalized likelihood ratio statistic. Within an extensive simulation study, we compare the newly proposed control charts using the median run length as a performance criterion.

Attunement in Music Therapy for Young Children with Autism: Revisiting Qualities of Relationship as Mechanisms of Change.

This study examined whether musical and emotional attunement predicts changes in improvisational music therapy with children with autism (4-7 years, N = 101, majority: no/limited speech, low IQ), assessed over 12 months. Attunement, as observed from session videos, and changes in generalized social skills, judged by blinded assessors and parents, were evaluated using standardized tools (Assessment of the Quality of Relationship, Improvisational Music Therapy Principles, ADOS, SRS). In contrast to the smaller pilot, we did not find significant effects between attunement and changes in outcomes, only tendencies in the same direction are observed. Findings suggest that symptom severity is associated with the therapist's ability to attune to the child. They further raise questions concerning outcome selection and user involvement.

The Therapeutic Relationship as Predictor of Change in Music Therapy with Young Children with Autism Spectrum Disorder.

This study examined whether the therapeutic relationship in music therapy with children with Autism Spectrum Disorder predicts generalized changes in social skills. Participants (4-7 years, N = 48) were assessed at baseline, 5 and 12 months. The therapeutic relationship, as observed from session videos, and the generalized change in social skills, as judged by independent blinded assessors and parents, were evaluated using standardized tools (Assessment of the Quality of Relationship; ADOS; SRS). Linear mixed effect models showed significant interaction effects between the therapeutic relationship and several outcomes at 5 and 12 months. We found the music therapeutic relationship to be an important predictor of the development of social skills, as well as communication and language specifically.

Detection of spatial change points in the mean and covariances of multivariate simultaneous autoregressive models.

In this paper, we propose a test procedure to detect change points of multidimensional autoregressive processes. The considered process differs from typical applied spatial autoregressive processes in that it is assumed to evolve from a predefined center into every dimension. Additionally, structural breaks in the process can occur at a certain distance from the predefined center. The main aim of this paper is to detect such spatial changes. In particular, we focus on shifts in the mean and the autoregressive parameter. The proposed test procedure is based on the likelihood-ratio approach. Eventually, the goodness-of-fit values of the estimators are compared for different shifts. Moreover, the empirical distribution of the test statistic of the likelihood-ratio test is obtained via Monte Carlo simulations. We show that the generalized Gumbel distribution seems to be a suitable limiting distribution of the proposed test statistic. Finally, we discuss the detection of lung cancer in computed tomography scans and illustrate the proposed test procedure.

Analysis of phytostanyl fatty acid esters in enriched foods via UHPLC-APCI-MS.

A method for the analysis of phytostanyl fatty acid esters, the functional ingredients of cholesterol-lowering enriched foods, was developed. The procedure is based on (i) separation of the intact esters via reversed-phase ultrahigh-performance liquid chromatography; (ii) detection by atmospheric pressure chemical ionization-mass spectrometry; and (iii) quantitation using selected ion monitoring (SIM) mode. Employing a C8 column, phytostanyl fatty acid esters sharing the same stanol nucleus could be separated according to the esterified fatty acids while esters with different stanol moieties could be distinguished via SIM based on the formation of an intense fragment ion [M - fatty acid + H](+). The suitability of the approach was demonstrated using different types of enriched foods reflecting the diversity in potential matrices (skimmed milk drinking yogurt, margarine, and soft-cheese-style spread). The developed methodology extends the analytical basis for authenticity and quality assessments of functional foods enriched with phytostanyl fatty acid esters.

Mode shaping in semiconductor broad area lasers by monolithically integrated phase structures.

By broadening the stripe width of the active waveguide region, it is possible to extract high optical powers from semiconductor broad area lasers. However, a weak output beam quality, optical filamentation, and high peak power densities will result, which are invoked by the amplification of higher order modes. We show an approach to influence the optical field inside the resonator by integrating optical phase structures directly into the waveguide. Those elements offer the possibility to enlarge the active gain area for the desired fundamental laser mode, while additional diffraction losses for higher order modes are generated, thus achieving an improved beam quality. We report on considerations in designing those elements and demonstrate a first experimental realization.

Biological activity of ruthenium and osmium arene complexes with modified paullones in human cancer cells.

In an attempt to combine the ability of indolobenzazepines (paullones) to inhibit cyclin-dependent kinases (Cdks) and that of platinum-group metal ions to interact with proteins and DNA, ruthenium(II) and osmium(II) arene complexes with paullones were prepared, expecting synergies and an increase of solubility of paullones. Complexes with the general formula [M(II)Cl(η(6)-p-cymene)L]Cl, where M=Ru (1, 3) or Os (2, 4), and L=L(1) (1, 2) or L(2) (3, 4), L(1)=N-(9-bromo-7,12-dihydroindolo[3,2-d][1]-benzazepin-6(5H)-yliden-N'-(2-hydroxybenzylidene)azine and L(2)=N-(9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6-yl)-N'-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl-methylene]azinium chloride (L(2)(*)HCl), were now investigated regarding cytotoxicity and accumulation in cancer cells, impact on the cell cycle, capacity of inhibiting DNA synthesis and inducing apoptosis as well as their ability to inhibit Cdk activity. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay yielded IC(50) values in the nanomolar to low micromolar range. In accordance with cytotoxicity data, the BrdU assay showed that 1 is the most and 4 the least effective of these compounds regarding inhibition of DNA synthesis. Effects on the cell cycle are minor, although concentration-dependent inhibition of Cdk2/cyclin E activity was observed in cell-free experiments. Induction of apoptosis is most pronounced for complex 1, accompanied by a low fraction of necrotic cells, as observed by annexin V-fluorescein isothiocyanate/propidium iodide staining and flow cytometric analysis.

Community-dwelling persons with dementia: what do they need? What do they demand? What do they do? A systematic review on the subjective experiences of persons with dementia.

OBJECTIVES: Including the perspectives of persons with dementia (PwD) is essential in order to organize care structures for them. With this systematic review, we set out to screen the existing scientific evidence on self-expressions of community-dwelling individuals with dementia in order to provide a research base for developing an intervention for persons in early stages of the disease. The leading research questions for this review are: What needs do PwD living at home express? What are their subjective demands? What do they do to cope with their situation? METHODS: We performed a systematic literature review of review publications on subjective experiences of PwD. The publications were analysed using MAXQDA 10 to perform a thematic analysis. RESULTS: We identified 41 relevant reviews, of which 6 met our inclusion criteria. PwD experience the whole range of human emotions. Their needs and demands do not differ significantly from those of other groups of patients with chronic conditions. Coming to terms with the disease and maintaining normality appeared to be major themes. With regard to expectations from the side of professional health care, the need for accompanying, continuous support and counselling appeared to be central. Furthermore, disclosure of diagnosis represents a critical stage for PwD, but our findings indicated that they prefer to be included in this process. CONCLUSIONS: PwD are well able to express their needs. They should be included in research since they can provide valuable findings. Furthermore, those findings should be implemented in applied dementia care.

Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages.

Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization-deficient GR (GR(dim)) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-α is normally regulated in these mice, but down-regulation of IL-6 and IL-1ß is diminished. LPS-treated macrophages derived from GR(dim) mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL-1 receptor antagonist improved survival of GR(dim) mice and mice lacking the GR in macrophages (GR(LysMCre)) mice. This suggests that regulation of IL-1ß in macrophages by GCs is pivotal to control sepsis.

Effect of elevation resolution on evapotranspiration simulations using MODFLOW.

Surface elevations represented in MODFLOW head-dependent packages are usually derived from digital elevation models (DEMs) that are available at much high resolution. Conventional grid refinement techniques to simulate the model at DEM resolution increases computational time, input file size, and in many cases are not feasible for regional applications. This research aims at utilizing the increasingly available high resolution DEMs for effective simulation of evapotranspiration (ET) in MODFLOW as an alternative to grid refinement techniques. The source code of the evapotranspiration package is modified by considering for a fixed MODFLOW grid resolution and for different DEM resolutions, the effect of variability in elevation data on ET estimates. Piezometric head at each DEM cell location is corrected by considering the gradient along row and column directions. Applicability of the research is tested for the lower Rio Grande (LRG) Basin in southern New Mexico. The DEM at 10 m resolution is aggregated to resampled DEM grid resolutions which are integer multiples of MODFLOW grid resolution. Cumulative outflows and ET rates are compared at different coarse resolution grids. Results of the analysis conclude that variability in depth-to-groundwater within the MODFLOW cell is a major contributing parameter to ET outflows in shallow groundwater regions. DEM aggregation methods for the LRG Basin have resulted in decreased volumetric outflow due to the formation of a smoothing error, which lowered the position of water table to a level below the extinction depth.

GC-based analysis of plant stanyl fatty acid esters in enriched foods.

Approaches for the capillary gas chromatographic (GC) based analysis of intact plant stanyl esters in enriched foods were developed. Reference compounds were synthesized by enzyme-catalyzed transesterifications. Their identities were confirmed by means of mass spectrometry. Using a medium polar trifluoropropylmethyl polysiloxane stationary phase, long-chain plant stanyl esters could be separated according to their stanol moieties and their fatty acid chains. Thermal degradation during GC analysis was compensated by determining response factors; calibrations were performed for ten individual plant stanyl esters. For the analysis of low-fat products (skimmed milk drinking yogurts), the GC separation was combined with a "fast extraction" under acidic conditions. For fat-based foods (margarines), online coupled LC-GC offered an elegant and efficient way to avoid time-consuming sample preparation steps. The robust and rapid methods allow conclusions on both, the stanol profiles and the fatty acid moieties, and thus provide a basis for the authentication of this type of functional food ingredients.

Home-based music therapy--a systematic overview of settings and conditions for an innovative service in healthcare.

BACKGROUND: Almost every Western healthcare system is changing to make their services more centered around out-patient care. In particular, long-term or geriatric patients who have been discharged from the hospital often require home-based care and therapy. Therefore, several programs have been developed to continue the therapeutic process and manage the special needs of patients after discharge from hospital. Music therapy has also moved into this field of healthcare service by providing home-based music therapy (HBMT) programs. This article reviews and summarizes the settings and conditions of HBMT for the first time. METHODS: The following databases were used to find articles on home-based music therapy: AMED, CAIRSS, EMBASE, MEDLINE, PsychINFO, and PSYNDEX. The search terms were "home-based music therapy" and "mobile music therapy". Included articles were analyzed with respect to participants as well as conditions and settings of HBMT. Furthermore, the date of publication, main outcomes, and the design and quality of the studies were investigated. RESULTS: A total of 20 international publications, 11 clinical studies and nine reports from practice, mainly from the United States (n = 8), were finally included in the qualitative synthesis. Six studies had a randomized controlled design and included a total of 507 patients. The vast majority of clients of HBMT are elderly patients living at home and people who need hospice and palliative care. Although settings were heterogeneous, music listening programs played a predominant role with the aim to reduce symptoms like depression and pain, or to improve quality of life and the relationship between patients and caregivers as primary endpoints. CONCLUSIONS: We were able to show that HBMT is an innovative service for future healthcare delivery. It fits with the changing healthcare system and its conditions but also meets the therapeutic needs of the increasing number of elderly and severely impaired people. Apart from music therapists, patients and their families HBMT is also interesting as a blueprint for home based care for other groups of caregivers.

Tableting and tablet properties of alginates: characterisation and potential for Soft Tableting.

The aim of the study was to evaluate the suitability of alginates for Soft Tableting. For this purpose the compaction properties of alginates, varying in molecular weight, guluronic acid/mannuronic acid ratio and salt, were investigated and compared to MCC. Based on the mechanical properties, the suitability of the tested excipients for Soft Tableting was predicted. In order to test the prediction the tested materials were used to tablet enteric coated pellets, which served as a pressure sensitive material. The tableting behaviour was analysed by the 3-D modeling technique. The tablet properties were analysed by determining the elastic recovery and the compactibility. Alginates in general deformed elastically. The compression behaviour depended on the chemical composition of the alginates with sodium alginates being more elastic than potassium alginates. Tablets containing alginates with low guluronic acid content exhibited higher elasticity than tablets with alginates having a low mannuronic acid content. The plasticity of potassium alginates was higher than for sodium alginates. However, the plasticity of all tested alginates was lower than the plasticity of MCC. The compactibility of the tested alginates was sufficient. The proposed prediction, which states that tableting excipients with higher elasticity are more suitable for tableting sensitive materials than plastic excipients, was valid for the tested materials. The elastic alginates inflicted less damage on the pellets than the plastic MCC. Thus, all alginates were more appropriate for tableting pressure sensitive materials than MCC.

Material and tablet properties of pregelatinized (thermally modified) Dioscorea starches.

The material and tablet formation properties of pregelatinized (thermally modified) forms of four Dioscorea starches have been investigated. Dioscorea starches were pregelatinized followed by either oven drying (PS) or freeze drying (FD) and used as excipient in direct compression. The physicochemical, morphological and material properties of the pregelatinized starches have been investigated. The tablet formation properties were assessed using the 3-D modeling parameters, the Heckel equation and the force-displacement profiles. The tablet properties were evaluated using the elastic recovery, compactibility plots and the disintegration test. The results indicate that pregelatinization improved the compressibility and flowability of the Dioscorea starches. The high bulk and tap densities of PS coupled with their good flowability offer a unique possibility of the starches being used as filler in capsule formulations. The modified starches generally showed differences in their time and pressure dependent deformation behaviour. PS exhibited higher elasticity during tableting. FD Chinese and FD Bitter showed higher plasticity and low fast elastic deformation than the PS forms of the starches indicating that the FD starches undergo the highest plastic deformation. However, FD starches generally showed higher compactibility compared to the PS forms of the Dioscorea starches. While FD White and FD Water showed fast disintegration time and high compactibility, FD Chinese and FD Bitter were non-disintegrating and showed high compactibility. The high compactibility observed with the FD starches appears to be as a result of material change occurring during tableting probably due to the effect of temperature or pressure or a combination of both factors. Thus, FD White and FD Water starches could be useful when high crushing force and fast disintegration are of concern while FD Chinese and FD Bitter, which were non-disintegrating, could find application as excipients for controlled drug delivery.

Metal-based paullones as putative CDK inhibitors for antitumor chemotherapy.

Paullones constitute a class of potent cyclin-dependent kinase inhibitors. To overcome the insufficient solubility and bioavailability, which hamper their potential medical application, we aim at the development of metal-based derivatives. Two types of paullone ligands, L (1) - L (3) and L (4) , with different locations of metal-binding sites, were prepared. They were found to form organometallic complexes of the general formula [M (II)Cl(eta (6)- p-cymene)L]Cl ( 1- 4, L = L (1) - L (4) ; a, M = Ru; b, M = Os). The complexes were characterized by X-ray crystallography, one- and two-dimensional NMR spectroscopy and other physical methods. Complexes 1- 3, with a coordinated amidine unit, were found to undergo E/ Z isomerization in solution. The reaction was studied by NMR spectroscopy, and activation parameters Delta H (double dagger) and Delta S (double dagger) were determined. Antiproliferative activity in the low micromolar range was observed in vitro in three human cancer cell lines by means of MTT assays. (3)H-Thymidine incorporation assays revealed the compounds to lower the rate of DNA synthesis, and flow cytometric analyses showed cell cycle arrest mainly in G 0/ G 1 phase.

Germ line transmission and expression of an RNAi cassette in mice generated by a lentiviral vector system.

We have used a lentiviral delivery system (LentiLox3.7) to generate transgenic mice harbouring RNA interference (RNAi) against the hepatocyte nuclear factor 4 gamma (HNF4gamma). HNF4gamma is a nuclear receptor with unknown function. Our analyses performed on founder (F(0)) and first generation (F(1)) mice revealed mosaicism in F(0) founders and a low efficiency of transgenesis (6%) in F(1) mice. These data, together with the observation of multiple silenced transgenes, do not favour the use of LentiLox3.7 lentivirus for transgenesis. Despite the low efficiency of transgenesis, we achieved a tissue-dependent knockdown of HNF4gamma expression in some mice.

The first ruthenium-based paullones: syntheses, X-ray diffraction structures, and spectroscopic and antiproliferative properties in vitro.

Two novel paullone derivatives, namely, 6-(alpha-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L1) and 9-bromo-6-(alpha-picolylamino)-7,12-dihydroindolo[3,2-d][1]benzazepine (L2), have been prepared. The reaction of cis-[RuCl2(DMSO)4] (DMSO=dimethyl sulfoxide) with L1 and L2 in a 1:1 molar ratio in dry ethanol at 50 degrees C afforded the complexes trans-[RuIICl2(DMSO)2L1] (1a) and trans-[RuIICl2(DMSO)2L2] (1b) in 26 and 30% yield, respectively. The reaction carried out from the same starting compounds in a 1:2 molar ratio at 75 degrees C led to the formation of [RuIICl(DMSO)(L1)2]Cl (2a) and [RuIICl(DMSO)(L2)2]Cl (2b) in 16 and 23% yield, correspondingly. The products were characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, electrospray ionization mass spectrometry, IR spectroscopy, electronic spectra, cyclic voltammetry, and X-ray crystallography (L1, L2, 1a, and 2b). Complexes 2a and 2b exhibit remarkable antiproliferative activity in three human carcinoma cell lines, A549 (non-small cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma). The novel complexes show an intercalative mode of interaction with DNA, which may render them attractive alternatives to metal compounds with a coordinative mode of interaction.

Macrophages and neutrophils are the targets for immune suppression by glucocorticoids in contact allergy.

Glucocorticoids (GCs) are widely used in the treatment of allergic skin conditions despite having numerous side effects. Here we use Cre/loxP-engineered tissue- and cell-specific and function-selective GC receptor (GR) mutant mice to identify responsive cell types and molecular mechanisms underlying the antiinflammatory activity of GCs in contact hypersensitivity (CHS). CHS was repressed by GCs only at the challenge phase, i.e., during reexposure to the hapten. Inactivation of the GR gene in keratinocytes or T cells of mutant mice did not attenuate the effects of GCs, but its ablation in macrophages and neutrophils abolished downregulation of the inflammatory response. Moreover, mice expressing a DNA binding-defective GR were also resistant to GC treatment. The persistent infiltration of macrophages and neutrophils in these mice is explained by an impaired repression of inflammatory cytokines and chemokines such as IL-1beta, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and IFN-gamma-inducible protein 10. In contrast TNF-alpha repression remained intact. Consequently, injection of recombinant proteins of these cytokines and chemokines partially reversed suppression of CHS by GCs. These studies provide evidence that in contact allergy, therapeutic action of corticosteroids is in macrophages and neutrophils and that dimerization GR is required.