Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Colorado Training Needs Assessment

The Colorado Department of Human Services (CO DHS) has contracted with the Cutler Institute for Health and Social Policy to assess the professional development needs of child welfare caseworkers, case aides, and supervisors. This needs assessment will help guide the development of the new Child Welfare Training Academy established by Governor Bill Ritter in May 2009. The Academy will provide child welfare professionals across the state with the training, skills and knowledge to better protect the state\u27s most vulnerable children from abuse and neglect

Scaling in Complex Systems: Analytical Theory of Charged Pores

In this paper we find an analytical solution of the equilibrium ion distribution for a toroidal model of a ionic channel, using the Perfect Screening Theorem (PST). The ions are charged hard spheres, and are treated using a variational Mean Spherical Approximation (VMSA) . Understanding ion channels is still a very open problem, because of the many exquisite tuning details of real life channels. It is clear that the electric field plays a major role in the channel behaviour, and for that reason there has been a lot of work on simple models that are able to provide workable theories. Recently a number of interesting papers have appeared that discuss models in which the effect of the geometry, excluded volume and non-linear behaviour is considered. We present here a 3D model of ionic channels which consists of a charged, deformable torus with a circular or elliptical cross section, which can be flat or vertical (close to a cylinder). Extensive comparisons to MC simulations were performed. The new solution opens new possibilities, such as studying flexible pores, and water phase transformations inside the pores using an approach similar to that used on flat crystal surfaces

High frequency of lumbar fusion in patients denied surgical treatment of the sacroiliac joint

Purpose: Effective treatment of medical conditions relies on proper diagnosis. Clinical trials show the safety and effectiveness of sacroiliac joint (SIJ) fusion in patients with chronic SI joint dysfunction. To what extent is the condition under recognised? Objective: To determine whether under recognition of SIJ pain affects healthcare trajectories in Spanish patients with low back pain. Methods: Retrospective study of characteristics and consequences of 189 patients with persistent SIJ pain seen in an outpatient neurosurgery clinic. Results: Patients with SIJ pain who were denied surgical treatment had a longer pain duration, higher likelihood of prior lumbar fusion, and a high rate (63%) of lumbar fusion within 2 years prior to SIJ pain diagnosis, which, in most cases, provided little benefit. Conclusions: Lack of knowledge of the role of the SIJ in chronic low back pain probably results in diagnostic confusion and may lead to misdirected treatment

The mechanical energetics of walking across the adult lifespan

Purpose Understanding what constitutes normal walking mechanics across the adult lifespan is crucial to the identification and intervention of early decline in walking function. Existing research has assumed a simple linear alteration in peak joint powers between young and older adults. The aim of the present study was to quantify the potential (non)linear relationship between age and the joint power waveforms of the lower limb during walking. Methods This was a pooled secondary analysis of the authors’ (MT, KD, JJ) and three publicly available datasets, resulting in a dataset of 278 adults between the ages of 19 to 86 years old. Three-dimensional motion capture with synchronised force plate assessment was performed during self-paced walking. Inverse dynamics were used to quantity joint power of the ankle, knee, and hip, which were time-normalized to 100 stride cycle points. Generalized Additive Models for location, scale and shape (GAMLSS) was used to model the effect of cycle points, age, walking speed, stride length, height, and their interaction on the outcome of each joint’s power. Results At both 1m/s and 1.5 m/s, A2 peaked at the age of 60 years old with a value of 3.09 (95% confidence interval [CI] 2.95 to 3.23) W/kg and 3.05 (95%CI 2.94 to 3.16), respectively. For H1, joint power peaked with a value of 0.40 (95%CI 0.31 to 0.49) W/kg at 1m/s, and with a value of 0.78 (95%CI 0.72 to 0.84) W/kg at 1.5m/s, at the age of 20 years old. For H3, joint power peaked with a value of 0.69 (95%CI 0.62 to 0.76) W/kg at 1m/s, and with a value of 1.38 (95%CI 1.32 to 1.44) W/kg at 1.5m/s, at the age of 70 years old. Conclusions Findings from this study do not support a simple linear relationship between joint power and ageing. A more in-depth understanding of walking mechanics across the lifespan may provide more opportunities to develop early clinical diagnostic and therapeutic strategies for impaired walking function. We anticipate that the present methodology of pooling data across multiple studies, is a novel and useful research method to understand motor development across the lifespan

A Dynamic Model of Unemployment with Migration and Delayed Policy Intervention

The purpose of this paper is to build and analyse a model of unemployment, where jobs search is open to both natives and migrant workers. Markets and government intervention respond jointly to unemployment when creating new jobs. Full employment of resources is the focal point of policy action, stimulating vacancy creation. We acknowledge that policy is implemented with delays, and capture labour market outcomes by building a non-linear dynamic system. We observe jobs separation and matching, and extend our model to an open economy with migration and delayed policy intervention meant to reduce unemployment. We analyse the stability behaviour of the resulting equilibrium for our dynamic system, including models with Dirac and weak kernels. We simulate our model with alternative scenarios, where policy action towards jobs creation considers both migration and unemployment, or just unemployment

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD

Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

Chiral Generations on Intersecting 5-branes in Heterotic String Theory

We show that there exist two 27 and one 27 bar of E6, net one D=4, N=1 chiral matter supermultiplet as zero modes localized on the intersection of two 5-branes in the E8 x E8 heterotic string theory. The smeared intersecting 5-brane solution is used via the standard embedding to construct a heterotic background, which provides, after a compactification of some of the transverse dimensions, a five-dimensional Randall-Sundrum II like brane-world set-up in heterotic string theory. As a by-product, we present a new proof of anomaly cancellation between those from the chiral matter and the anomaly inflow onto the brane without small instanton.Comment: 26 pages, 5 figures; references added, typo correcte