Patient Satisfaction with Psychological Treatment on a Voluntary Inpatient Psychiatric Unit.

Despite the empirical literature suggesting the benefits of providing patient support and psychotherapy, research examining patient satisfaction with psychological services integrated within inpatient psychiatric treatment settings remains scarce. A sample of 122 adults within a voluntary inpatient psychiatric unit, who were receiving psychological services completed a satisfaction questionnaire. Overall, participants reported high levels of satisfaction with psychological services and perceived them as helpful to their overall care.

On cheap entropy-sparsified regression learning.

Regression learning is one of the long-standing problems in statistics, machine learning, and deep learning (DL). We show that writing this problem as a probabilistic expectation over (unknown) feature probabilities - thus increasing the number of unknown parameters and seemingly making the problem more complex-actually leads to its simplification, and allows incorporating the physical principle of entropy maximization. It helps decompose a very general setting of this learning problem (including discretization, feature selection, and learning multiple piece-wise linear regressions) into an iterative sequence of simple substeps, which are either analytically solvable or cheaply computable through an efficient second-order numerical solver with a sublinear cost scaling.

eSPA+: Scalable Entropy-Optimal Machine Learning Classification for Small Data Problems.

Classification problems in the small data regime (with small data statistic T and relatively large feature space dimension D) impose challenges for the common machine learning (ML) and deep learning (DL) tools. The standard learning methods from these areas tend to show a lack of robustness when applied to data sets with significantly fewer data points than dimensions and quickly reach the overfitting bound, thus leading to poor performance beyond the training set. To tackle this issue, we propose eSPA+, a significant extension of the recently formulated entropy-optimal scalable probabilistic approximation algorithm (eSPA).

The examination of sleep hygiene, quality of life, and schizotypy in young adults.

The co-occurrence of sleep disruption and schizophrenia-spectrum symptomology is common, with current research supporting the use of interventions, such as cognitive behavioral therapy for insomnia (CBTi), which include sleep hygiene education. Sleep hygiene refers to patterns of pre-sleep behaviors that can promote or impair sleep. These behaviors are easily identified and modifiable, potentially holding promise as targets of research and clinical practice.

Systematic calculation of finite-time mixed singular vectors and characterization of error growth for persistent coherent atmospheric disturbances over Eurasia.

Singular vectors (SVs) have long been employed in the initialization of ensemble numerical weather prediction (NWP) in order to capture the structural organization and growth rates of those perturbations or "errors" associated with initial condition errors and instability processes of the large scale flow. Due to their (super) exponential growth rates and spatial scales, initial SVs are typically combined empirically with evolved SVs in order to generate forecast perturbations whose structures and growth rates are tuned for specified lead-times. Here, we present a systematic approach to generating finite time or "mixed" SVs (MSVs) based on a method for the calculation of covariant Lyapunov vectors and appropriate choices of the matrix cocycle.

Observational Needs for Improving Ocean and Coupled Reanalysis, S2S Prediction, and Decadal Prediction.

Developments in observing system technologies and ocean data assimilation (DA) are symbiotic. New observation types lead to new DA methods and new DA methods, such as coupled DA, can change the value of existing observations or indicate where new observations can have greater utility for monitoring and prediction. Practitioners of DA are encouraged to make better use of observations that are already available, for example, taking advantage of strongly coupled DA so that ocean observations can be used to improve atmospheric analyses and vice versa.

Global patterns of change and variation in sea surface temperature and chlorophyll a.

Changes over the scale of decades in oceanic environments present a range of challenges for management and utilisation of ocean resources. Here we investigate sources of global temporal variation in Sea Surface Temperature (SST) and Ocean Colour (Chl-a) and their co-variation, over a 14 year period using statistical methodologies that partition sources of variation into inter-annual and annual components and explicitly account for daily auto-correlation. The variation in SST shows bands of increasing variability with increasing latitude, while the analysis of annual variability in Chl-a shows mostly mid-latitude high variability bands.

Intrinsic processes drive variability in basal melting of the Totten Glacier Ice Shelf.

Over the period 2003-2008, the Totten Ice Shelf (TIS) was shown to be rapidly thinning, likely due to basal melting. However, a recent study using a longer time series found high interannual variability present in TIS surface elevation without any apparent trend. Here we show that low-frequency intrinsic ocean variability potentially accounts for a large fraction of the variability in the basal melting of TIS.

Decadal-Scale Forecasting of Climate Drivers for Marine Applications.

Climate influences marine ecosystems on a range of time scales, from weather-scale (days) through to climate-scale (hundreds of years). Understanding of interannual to decadal climate variability and impacts on marine industries has received less attention. Predictability up to 10 years ahead may come from large-scale climate modes in the ocean that can persist over these time scales.

Sources of heterogeneous variability and trends in Antarctic sea-ice.

While the Northern Hemisphere sea-ice has uniformly declined over the past several decades, the observed sea-ice in the Southern Hemisphere has exhibited regions of increase and decrease. Here we use a comprehensive set of ocean-sea-ice simulations (1990-2007) to elucidate the drivers of the observed heterogeneous sea-ice trends. We show wind variability is an important determinant of the heterogeneous pattern of the variability and trends in Southern Hemisphere sea-ice.

Subgrid modelling for geophysical flows.

Recently developed closure-based and stochastic model approaches to subgrid-scale modelling of eddy interactions are reviewed. It is shown how statistical dynamical closure models can be used to self-consistently calculate the eddy damping and stochastic backscatter parameters, required in large eddy simulations (LESs), from higher resolution simulations. A closely related direct stochastic modelling scheme that is more generally applicable to complex models is then described and applied to LESs of quasi-geostrophic turbulence of the atmosphere and oceans.

Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer.

Constitutively activated STAT3 and STAT5 are expressed in a wide variety of human malignancies including solid and hematopoietic cancers and often correlate with a poor prognosis and resistance to multiple therapies. Given the well established role of STAT3 in tumorigenesis, inhibition of Janus-activated kinase 2 (JAK2) activity might represent an attractive therapeutic approach. Using a mouse model of colitis-induced colorectal cancer, we show that a novel, orally active, selective JAK2 inhibitor, CEP-33779, induced regression of established colorectal tumors, reduced angiogenesis, and reduced proliferation of tumor cells.

Optimization of a novel kinase inhibitor scaffold for the dual inhibition of JAK2 and FAK kinases.

The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression.

The phosphatidylinositol 3-kinase inhibitor LY 294002 inhibits GlyT1-mediated glycine uptake.

The actions of neurotransmitter glycine are regulated by the Na+/Cl(-) dependent high-affinity glycine transporters, GlyT1 and GlyT2. These two members of the SLC6 transport family have been cloned and extensively characterized, however relatively little is known regarding their modulation. In the present study, glycine uptake in primary cultures of rat embryonic cortex has been characterized and the effects of the phosphatidylinositol 3 (PI3) kinase inhibitors LY 294002 and wortmannin on GlyT1- and GlyT2-mediated glycine uptake were investigated.

Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease.

Three mouse models of Alzheimer's disease (AD) were used to assess changes in gene expression potentially critical to amyloid beta-peptide (Abeta)-induced neuronal dysfunction. One mouse model harbored homozygous familial AD (FAD) knock-in mutations in both, amyloid precursor protein (APP) and presenilin 1 (PS-1) genes (APP(NLh/NLh)/PS-1(P264L/P264L)), the other two models harbored APP over-expression of FAD mutations (Tg2576) with the PS-1 knock-in mutation at either one or two alleles. These mouse models of AD had varying levels of Abeta40 and Abeta42 and different latencies and rates of Abeta deposition in brain.

Protein tyrosine phosphatases are up-regulated and participate in cell death induced by polyglutamine expansion.

Polyglutamine expansion is the cause of several neurodegenerative diseases. An in vitro model of polyglutamine-induced neuronal cell death was developed using truncated mutant huntingtin (Htt) and PC12 cells. Cell death was specifically observed in cells expressing a truncated mutant huntingtin-green fluorescence protein (GFP) fusion protein with 118 glutamine repeats (Gln(118)), as demonstrated by the release of lactate dehydrogenase (LDH).

Mixed lineage kinase activity of indolocarbazole analogues.

The MLK1-3 activity for a series of analogues of the indolocarbazole K-252a is reported. Addition of 3,9-bis-alkylthiomethyl groups to K-252a results in potent and selective MLK inhibitors. The in vitro and in vivo survival promoting activity of bis-isopropylthiomethyl-K-252a (16, CEP-11004/KT-8138) is reported.

CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with Abeta-induced cortical neuron apoptosis.

Although the mechanism of neuronal death in Alzheimer's disease (AD) has yet to be elucidated, a putative role for c-jun in this process has emerged. Thus, it was of interest to delineate signal transduction pathway(s) which regulate the transcriptional activity of c-jun, and relate these to alternate gene inductions and biochemical processes associated with beta-amyloid (Abeta) treatment. In this regard, the survival promoting activity of CEP-1347, an inhibitor of the stress-activated/c-jun N-terminal (SAPK/JNK) kinase pathway, was evaluated against Abeta-induced cortical neuron death in vitro.

CEP-1347 (KT7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults.

The c-Jun N-terminal kinase signaling cascade appears to play a role in some cases of cell death, including neuronal apoptosis. CEP-1347 (KT7515), an indolocarbazole of the K252a family, blocks this stress signaling cascade and promotes survival. Here, we used CEP-1347 to probe whether neuronal death pathways activated by distinct insults also possess elements in common.

Exploration of the importance of the P2-P3-NHCO-moiety in a potent di- or tripeptide inhibitor of calpain I: insights into the development of nonpeptidic inhibitors of calpain I.

Calpain I, an intracellular cysteine protease, has been implicated in the neurodegeneration following an episode of cerebral ischemia. In this paper, we report on a series of peptidomimetic ketomethylene and carbamethylene inhibitors of recombinant human calpain I (rh calpain I). Our study reveals that the -NHCO-moiety (possible hydrogen-bonding site) at the P2-P3 region of a potent tripeptide or a dipeptide inhibitor of calpain I is not a strict requirement for enzyme recognition.

Synthesis and biological activity of a series of potent fluoromethyl ketone inhibitors of recombinant human calpain I.

Calpain I, an intracellular cysteine protease, has been implicated in the neurodegeneration following an episode of stroke. In this paper, we report on a series of potent dipeptide fluoromethyl ketone inhibitors of recombinant human calpain I (rh calpain I). SAR studies revealed that while calpain I tolerates a variety of hydrophobic groups at the P1 site, Leu at P2 is preferred.

Ontogeny of somatostatin mRNA-containing perikarya in the rat central nervous system.

The distribution of neuronal perikarya containing somatostatin mRNA in the developing rat brain was investigated with in situ hybridization histochemistry. This study describes the expression of somatostatin mRNA during selected perinatal stages and demonstrates regional changes in somatostatin mRNA expression at the single cell level. The mRNA expression closely parallels previously reported developmental localization of the peptide (Inagaki et al.

Coordinate hormonal and synaptic regulation of vasopressin messenger RNA.

Previous studies have shown that adrenalectomy augments arginine vasopressin (AVP) messenger RNA levels in the adult paraventricular nucleus. It is now demonstrated that unilateral lesions in the lateral septal nucleus enhance the adrenalectomy-induced expression of AVP mRNA. This effect was entirely ipsilateral to the lesion and most prominent in the rostral paraventricular nucleus and related nuclei.

Hormonal regulation of somatostatin messenger RNA.

The ability of gonadal steroids to regulate the expression of the somatostatin gene in several regions of the CNS was investigated with in situ hybridization histochemistry. The amount of somatostatin mRNA was found to be significantly decreased 2-3 weeks after ovariectomy or orchidectomy in the periventricular hypothalamus, the ventromedial nucleus of the hypothalamus, and the medial and central nuclei of the amygdala. Treatment of gonadectomized rats with estradiol benzoate or testosterone enanthate reversed this decrease in somatostatin mRNA.