Targeting Serotonin Transporters in the Treatment of Juvenile and Adolescent Depression

Depression is a serious public health concern. Many patients are not effectively treated, but in children and adolescents this problem is compounded by limited pharmaceutical options. Currently, the Food and Drug Administration approves only two antidepressants for use in these young populations. Both are selective serotonin reuptake inhibitors (SSRIs). Compounding matters further, they are therapeutically less efficacious in children and adolescents than in adults. Here, we review clinical and preclinical literature describing the antidepressant efficacy of SSRIs in juveniles and adolescents. Since the high-affinity serotonin transporter (SERT) is the primary target of SSRIs, we then synthesize these reports with studies of SERT expression/function during juvenile and adolescent periods. Preclinical literature reveals some striking parallels with clinical studies, primary among them is that, like humans, juvenile and adolescent rodents show reduced antidepressant-like responses to SSRIs. These findings underscore the utility of preclinical assays designed to screen drugs for antidepressant efficacy across ages. There is general agreement that SERT expression/function is lower in juveniles and adolescents than in adults. It is well established that chronic SSRI treatment decreases SERT expression/function in adults, but strikingly, SERT expression/function in adolescents is increased following chronic treatment with SSRIs. Finally, we discuss a putative role for organic cation transporters and/or plasma membrane monoamine transporter in serotonergic homeostasis in juveniles and adolescents. Taken together, fundamental differences in SERT, and putatively in other transporters capable of serotonin clearance, may provide a mechanistic basis for the relative inefficiency of SSRIs to treat pediatric depression, relative to adults

Canary in the coal mine: Lessons from the Jarrah Forest suggest long-term negative effects of phosphorus fertilizer on biodiverse restoration after surface mining

Despite nutrient enrichment having widely reported negative impacts on biodiversity, fertilizer is routinely applied in post mining restoration to enhance plant growth and establishment. Focusing on surface mine restoration (predominately bauxite and mineral sands), we outline the long-term negative impacts of fertilizer, particularly phosphorus fertilizer, on plant community composition, species richness, fire fuel loads, and belowground impacts on nutrient-cycling. We draw from extensive research in south-western Australia and further afield, noting the geographical coincidence of surface mining, phosphorus impoverished soil and high plant biodiversity. We highlight the trade-offs between rapid plant-growth under fertilisation and the longer-term effects on plant communities and diversity. We note that the initial growth benefits of fertilisation may not persist in water-limited environments: growth of unfertilised forests can eventually match that of fertilised forest, throwing doubt on the premise that fertilisation is necessary at all

Assessment of the impact of camshaft machining inputs on valve train sound quality using vibration analysis.

A study was undertaken to investigate the dependence of valve train sound quality on certain camshaft machining parameters. In particular, a sound quality issue referred to as camshaft chatter was investigated. Camshaft chatter refers to a noise caused by geometrical undulations on the camshaft lobes that excite valve train and cylinder head vibration modes during operation. The undulations are an artifact of the manufacturing process. The engine used in the study was a dual overhead camshaft (DOHC) V6. Eight different left-hand-side exhaust camshafts were manufactured with different, known combinations of the selected machining parameters. Each parameter was varied between a high and low setting. Tri-axial accelerometers were mounted at two locations on the cylinder head of the test engine, and extensive vibration data was collected for each camshaft. The vibration data was analyzed using a number of methods, including: time domain analysis, RMS analysis, angle domain variance analysis, and RPM-frequency analysis. After a method was developed to objectively quantify the severity of camshaft chatter, a main effects analysis was performed to assess the impact of the individual machining inputs. It was found that vibration of the camshaft grinding wheel had the largest impact on camshaft chatter, followed by vibration of the grinding wheel motor. Tension of the drive belt was also shown to impact the severity of the chatter phenomenon.Dept. of Mechanical, Automotive, and Materials Engineering. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2002 .D35. Source: Masters Abstracts International, Volume: 42-01, page: 0274. Adviser: G. Reader. Thesis (M.A.Sc.)--University of Windsor (Canada), 2002

Shift invariant preduals of ℓ₁(ℤ)

The Banach space ℓ<sub>1</sub>(ℤ) admits many non-isomorphic preduals, for example, C(K) for any compact countable space K, along with many more exotic Banach spaces. In this paper, we impose an extra condition: the predual must make the bilateral shift on ℓ<sub>1</sub>(ℤ) weak<sup>*</sup>-continuous. This is equivalent to making the natural convolution multiplication on ℓ<sub>1</sub>(ℤ) separately weak*-continuous and so turning ℓ<sub>1</sub>(ℤ) into a dual Banach algebra. We call such preduals <i>shift-invariant</i>. It is known that the only shift-invariant predual arising from the standard duality between C<sub>0</sub>(K) (for countable locally compact K) and ℓ<sub>1</sub>(ℤ) is c<sub>0</sub>(ℤ). We provide an explicit construction of an uncountable family of distinct preduals which do make the bilateral shift weak<sup>*</sup>-continuous. Using Szlenk index arguments, we show that merely as Banach spaces, these are all isomorphic to c<sub>0</sub>. We then build some theory to study such preduals, showing that they arise from certain semigroup compactifications of ℤ. This allows us to produce a large number of other examples, including non-isometric preduals, and preduals which are not Banach space isomorphic to c<sub>0</sub>

Teachers developing assessment for learning: impact on student achievement

While it is generally acknowledged that increased use of formative assessment (or assessment for learning) leads to higher quality learning, it is often claimed that the pressure in schools to improve the results achieved by students in externally-set tests and examinations precludes its use. This paper reports on the achievement of secondary school students who worked in classrooms where teachers made time to develop formative assessment strategies. A total of 24 teachers (2 science and 2 mathematics teachers, in each of six schools in two LEAs) were supported over a six-month period in exploring and planning their approach to formative assessment, and then, beginning in September 1999, the teachers put these plans into action with selected classes. In order to compute effect sizes, a measure of prior attainment and at least one comparison group was established for each class (typically either an equivalent class taught in the previous year by the same teacher, or a parallel class taught by another teacher). The mean effect size was 0.32

Parametric LTL on Markov Chains

This paper is concerned with the verification of finite Markov chains against parametrized LTL (pLTL) formulas. In pLTL, the until-modality is equipped with a bound that contains variables; e.g., $\Diamond_{\le x}\ \varphi$ asserts that $\varphi$ holds within $x$ time steps, where $x$ is a variable on natural numbers. The central problem studied in this paper is to determine the set of parameter valuations $V_{\prec p} (\varphi)$ for which the probability to satisfy pLTL-formula $\varphi$ in a Markov chain meets a given threshold $\prec p$, where $\prec$ is a comparison on reals and $p$ a probability. As for pLTL determining the emptiness of $V_{> 0}(\varphi)$ is undecidable, we consider several logic fragments. We consider parametric reachability properties, a sub-logic of pLTL restricted to next and $\Diamond_{\le x}$, parametric B\"uchi properties and finally, a maximal subclass of pLTL for which emptiness of $V_{> 0}(\varphi)$ is decidable.Comment: TCS Track B 201

{VeSTA} : a Tool to Verify the Correct Integration of a Component in a Composite Timed System

International audienceVesta is a push-button tool for checking the correct integration of a component in an environment, for component-based timed systems. By correct integration, we mean that the local properties of the component are preserved when this component is merged into an environment. This correctness is checked by means of a so-called divergencesensitive and stability-respecting timed tau-simulation, ensuring the preservation of all linear timed properties expressed in the logical formalism Mitl (Metric Interval Temporal Logic), as well as strong non-zenoness and deadlock-freedom. The development of the tool was guided by the architecture of the Open-Kronos tool. This allows, as additional feature, an easy connection of the models considered in Vesta to the Open- Caesar verification platform, and to the Open-Kronos tool

Ontogeny of NET expression and antidepressant-like response to desipramine in wild-type and SERT mutant mice

Abstract word count: 250 Introduction word count: 74