An overview of psychological and neurobiological mechanisms by which early negative experiences increase risk of mood disorders

Objective: Early life experiences are associated with severe and long-lasting effects on behavioural and emotional functioning, which in turn are thought to increase the risk for unipolar depression and other disorders of affect regulation. The neurobiological and psychological mechanisms through which adverse early life experiences confer risk are poorly understood. Method: Alterations in brain structure and function in limbic and prefrontal cortical regions have been linked to early negative experiences and to mood disorders. Results: There are a number of psychological domains that may be dysfunctional in people with mood disorders, and which, if the dysfunction occurs prior to onset of mood symptoms, may signify a risk factor for depression. Cognitive dysfunction has been examined in patients with mood disorders, with some suggestion that changes in cognitive function may antedate the onset of mood symptoms, and may be exacerbated in those who experienced early negative trauma. Social cognition, including emotion comprehension, theory of mind and empathy, represent under-studied domains of psychological function that may be negatively influenced by early adverse experience. Temperament and personality factors may also leave people vulnerable to mood instability. Conclusion: This review summarizes the evidence for dysfunction in each of these domains for people with mood disorders.

Evaluation of routine microbiological techniques for establishing the diagnosis of catheter-related bloodstream infection caused by coagulase-negative staphylococci

Microbiological diagnosis of catheter-related bloodstream infection (CR-BSI) is often based on isolation of indistinguishable micro-organisms from an explanted catheter tip and blood culture, confirmed by antibiograms. Whether phenotypic identification of coagulase-negative staphylococci (CoNS) allows an accurate diagnosis of CR-BSI to be established was evaluated. Eight patients with a diagnosis of CR-BSI had CoNS isolated from pure blood cultures and explanted catheter tips which were considered as indistinguishable strains by routine microbiological methods. For each patient, an additional three colonies of CoNS isolated from the blood and five from the catheter tip were subcultured and further characterized by antibiogram profiles, analytical profile index (API) biotyping and PFGE. PFGE distinguished more strains of CoNS compared to API biotyping or antibiograms (17, 10 and 11, respectively). By PFGE, indistinguishable micro-organisms were only isolated from pure blood and catheter tip cultures in four out of eight (50%) patients thus supporting the diagnosis of CR-BSI. In another patient, indistinguishable micro-organisms were identified in both cultures; however, other strains of CoNS were also present. The remaining three patients had multiple strains of CoNS, none of which were indistinguishable in the tip and blood cultures, thus questioning the diagnosis of CR-BSI. Phenotypic characterization of CoNS lacked discriminatory power. Current routine methods of characterizing a limited number of pooled colonies may generate misleading results as multiple strains may be present in the cultures. Multiple colonies should be studied using a rapid genotypic characterization method to confirm or refute the diagnosis of CR-BSI. © 2007 SGM.

The development of a modified dissolution method suitable for investigating powder mixtures

A novel dissolution method was developed, suitable for powder mixtures, based on the USP basket apparatus. The baskets were modified such that the powder mixtures were retained within the baskets and not dispersed, a potential difficulty that may arise when using conventional USP basket and paddle apparatus. The advantages of this method were that the components of the mixtures were maintained in close proximity, maximizing any drug:excipient interaction and leading to more linear dissolution profiles. Two weakly acidic model drugs, ibuprofen and acetaminophen, and a selection of pharmaceutical excipients, including potential dissolution-enhancing alkalizing agents, were chosen for investigation. Dissolution profiles were obtained for simple physical mixtures. The f1 fit factor values, calculated using pure drug as the reference material, demonstrated a trend in line with expectations, with several dissolution enhancers apparent for both drugs. Also, the dissolution rates were linear over substantial parts of the profiles. For both drugs, a rank order comparison between the f1 fit factor and calculated dissolution rate, obtained from the linear section of the dissolution profile, demonstrated a correlation using a significance level of P=0.05. The method was proven to be suitable for discriminating between the effects of excipients on the dissolution of the model drugs. The method design produced dissolution profiles where the dissolution rate was linear for a substantial time, allowing determination of the dissolution rate without mathematical transformation of the data. This method may be suitable as a preliminary excipient-screening tool in the drug formulation development process.

How innovation can alleviate negative consequences of demanding work contexts:The influence of climate for innovation on organizational outcomes

This study examines climate for innovation as a method by which negative organizational consequences of demanding work may be lessened. It was expected that a climate for innovation would enable employees to develop coping mechanisms or improved work-related processes which counteract negative consequences of work demands. Extending the job demands-resource model (Karasek, 1979), we predicted and found that among the sample of 22,696 respondents from 131 healthcare organizations, organizational climate for innovation alleviated the negative effects of work demands on organizational performance. Thus, this study informs climate theories and guides practitioners' efforts to support the employees. © 2007 The British Psychological Society.

Maintenance strategies affecting equipment performance

Proper maintenance of plant items is crucial for the safe and profitable operation of process plants, The relevant maintenance policies fall into the following four categories: (i) preventivejopportunistic/breakdown replacement policies, (ii) inspection/inspection-repair-replacernent policies, (iii) restorative maintenance policies, and (iv) condition based maintenance policies, For correlating failure times of component equipnent and complete systems, the Weibull failure distribution has been used, A new powerful method, SEQLIM, has been proposed for the estimation of the Weibull parameters; particularly, when maintenance records contain very few failures and many successful operation times. When a system consists of a number of replaceable, ageing components, an opporturistic replacernent policy has been found to be cost-effective, A simple opportunistic rrodel has been developed. Inspection models with various objective functions have been investigated, It was found that, on the assumption of a negative exponential failure distribution, all models converge to the same optimal inspection interval; provided the safety components are very reliable and the demand rate is low, When deterioration becomes a contributory factor to same failures, periodic inspections, calculated from above models, are too frequent, A case of safety trip systems has been studied, A highly effective restorative maintenance policy can be developed if the performance of the equipment under this category can be related to some predictive modelling. A novel fouling model has been proposed to determine cleaning strategies of condensers, Condition-based maintenance policies have been investigated. A simple gauge has been designed for condition monitoring of relief valve springs. A typical case of an exothermic inert gas generation plant has been studied, to demonstrate how various policies can be applied to devise overall maintenance actions.

NF-κB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle

Loss of skeletal muscle in cancer cachexia has a negative effect on both morbidity and mortality. The role of nuclear factor-κB (NF-κB) in regulating muscle protein degradation and expression of the ubiquitin-proteasome proteolytic pathway in response to a tumour cachectic factor, proteolysis-inducing factor (PIF), has been studied by creating stable, transdominant-negative, muscle cell lines. Murine C2C12 myoblasts were transfected with plasmids with a CMV promoter that had mutations at the serine phosphorylation sites required for degradation of I-κBα, an NF-κB inhibitory protein, and allowed to differentiate into myotubes. Proteolysis-inducing factor induced degradation of I-κBα, nuclear accumulation of NF-κB and an increase in luciferase reporter gene activity in myotubes containing wild-type, but not mutant, I-κBα, proteins. Proteolysis-inducing factor also induced total protein degradation and loss of the myofibrillar protein myosin in myotubes containing wild-type, but not mutant, plasmids at the same concentrations as those causing activation of NF-κB. Proteolysis-inducing factor also induced increased expression of the ubiquitin-proteasome pathway, as determined by 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the β-subunits of the proteasome, protein expression of 20S α-subunits and the 19S subunits MSSI and p42, as well as the ubiquitin conjugating enzyme, E214k, in cells containing wild-type, but not mutant, I-κBα. The ability of mutant I-κBα to inhibit PIF-induced protein degradation, as well as expression of the ubiquitin-proteasome pathway, confirms that both of these responses depend on initiation of transcription by NF-κB. © 2005 Cancer Research UK.

Role of protein kinase C and NF-kappa B in proteolysis-inducing factor-induced proteasome expression in C2C12 myotubes

Proteolysis-inducing factor (PIF) is a sulphated glycoprotein produced by cachexia-inducing tumours, which initiates muscle protein degradation through an increased expression of the ubiquitin–proteasome proteolytic pathway. The role of kinase C (PKC) in PIF-induced proteasome expression has been studied in murine myotubes as a surrogate model of skeletal muscle. Proteasome expression induced by PIF was attenuated by 4alpha-phorbol 12-myristate 13-acetate (100 nM) and by the PKC inhibitors Ro31-8220 (10 muM), staurosporine (300 nM), calphostin C (300 nM) and Gö 6976 (200 muM). Proteolysis-inducing factor-induced activation of PKCalpha, with translocation from the cytosol to the membrane at the same concentration as that inducing proteasome expression, and this effect was attenuated by calphostin C. Myotubes transfected with a constitutively active PKCalpha (pCO2) showed increased expression of proteasome activity, and a longer time course, compared with their wild-type counterparts. In contrast, myotubes transfected with a dominant-negative PKCalpha (pKS1), which showed no activation of PKCalpha in response to PIF, exhibited no increase in proteasome activity at any time point. Proteolysis-inducing factor-induced proteasome expression has been suggested to involve the transcription factor nuclear factor-kappaB (NF-kappaB), which may be activated through PKC. Proteolysis-inducing factor induced a decrease in cytosolic I-kappaBalpha and an increase in nuclear binding of NF-kappaB in pCO2, but not in pKS1, and the effect in wild-type cells was attenuated by calphostin C, confirming that it was mediated through PKC. This suggests that PKC may be involved in the phosphorylation and degradation of I-kappaBalpha, induced by PIF, necessary for the release of NF-kappaB from its inactive cytosolic complex.

Is gender a factor in perceived prison officer competence?

Background The introduction of women officers into HM Prison Service raised questions regarding women's ability to perform what had traditionally been a male role. Existing research is inconclusive as to whether female prison officers are as competent as male prison officers, and whether there are gender differences in job performance. This study examined prisoners' perceptions of male and female prison officers' performance. Hypotheses The hypotheses were that overall competence and professionalism ratings would not differ for men and women officers, but that there would be differences in how men and women were perceived to perform their roles. Women were expected to be rated as more communicative, more empathic and less disciplining. Method The Prison Officer Competency Rating Scale (PORS) was designed for this study. Ratings on the PORS for male and female officers were given by 57 adult male prisoners. Results There was no significant difference in prisoners' ratings of overall competence of men and women officers. Of the PORS subscales, there were no gender differences in Discipline and Control, Communication or Empathy, but there was a significant difference in Professionalism, where prisoners rated women as more professional. Conclusion The failure to find any differences between men and women in overall job competence, or on communication, empathy and discipline, as perceived by prisoners, suggests that men and women may be performing their jobs similarly in many respects. Women were rated as more professional, and items contributing to this scale related to respecting privacy and keeping calm in difficult situations, where there may be inherent gender biases. Copyright © 2005 Whurr Publishers Ltd.

Involvement of phosphoinositide 3-kinase and Akt in the induction of muscle protein degradation by proteolysis-inducing factor

In the present study the role of Akt/PKB (protein kinase B) in PIF- (proteolysis-inducing factor) induced protein degradation has been investigated in murine myotubes. PIF induced transient phosphorylation of Akt at Ser(473) within 30 min, which was attenuated by the PI3K (phosphoinositide 3-kinase) inhibitor LY294002 and the tyrosine kinase inhibitor genistein. Protein degradation was attenuated in myotubes expressing a dominant-negative mutant of Akt (termed DNAkt), compared with the wild-type variant, whereas it was enhanced in myotubes containing a constitutively active Akt construct (termed MyrAkt). A similar effect was observed on the induction of the ubiquitin-proteasome pathway. Phosphorylation of Akt has been linked to up-regulation of the ubiquitin-proteasome pathway through activation of NF-kappaB (nuclear factor kappaB) in a PI3K-dependent process. Protein degradation was attenuated by rapamycin, a specific inhibitor of mTOR (mammalian target of rapamycin), when added before, or up to 30 min after, addition of PIF. PIF induced transient phosphorylation of mTOR and the 70 kDa ribosomal protein S6 kinase. These results suggest that transient activation of Akt results in an increased protein degradation through activation of NF-kappaB and that this also allows for a specific synthesis of proteasome subunits.

A DEA model for units with negative data

In this paper we propose an alternative method for measuring efficiency of Decision making Units, which allows the presence of variables with both negative and positive values. The model is applied to data on the notional effluent processing system to compare the results with recent developed methods; Modified Slacks Based Model as suggested by Sharp et al (2007) and Range Directional Measures developed by Silva Portela et al (2004). A further example explores advantages of using the new model.

A semi-oriented radial measure for measuring the efficiency of decision making units with negative data, using DEA

Data Envelopment Analysis (DEA) is a nonparametric method for measuring the efficiency of a set of decision making units such as firms or public sector agencies, first introduced into the operational research and management science literature by Charnes, Cooper, and Rhodes (CCR) [Charnes, A., Cooper, W.W., Rhodes, E., 1978. Measuring the efficiency of decision making units. European Journal of Operational Research 2, 429–444]. The original DEA models were applicable only to technologies characterized by positive inputs/outputs. In subsequent literature there have been various approaches to enable DEA to deal with negative data. In this paper, we propose a semi-oriented radial measure, which permits the presence of variables which can take both negative and positive values. The model is applied to data on a notional effluent processing system to compare the results with those yielded by two alternative methods for dealing with negative data in DEA: The modified slacks-based model suggested by Sharp et al. [Sharp, J.A., Liu, W.B., Meng, W., 2006. A modified slacks-based measure model for data envelopment analysis with ‘natural’ negative outputs and inputs. Journal of Operational Research Society 57 (11) 1–6] and the range directional model developed by Portela et al. [Portela, M.C.A.S., Thanassoulis, E., Simpson, G., 2004. A directional distance approach to deal with negative data in DEA: An application to bank branches. Journal of Operational Research Society 55 (10) 1111–1121]. A further example explores the advantages of using the new model.

The four-factor taxonomy of relocation outcomes

Relocation, an intraorganizational geographical transfer, can be used for human resource development (HRD) because of the positive developmental effects it can induce. It is, thus, important for HRD professionals to understand the implications of relocation to ensure it is used appropriately and effectively as an HRD technique. Research on relocation is abundant but presently lacks integration. This article introduces the Four-Factor Taxonomy of Relocation Outcomes, which summarizes, organizes, and guides research in this area. The taxonomy provides researchers with four dimensions along which to consistently classify relocation outcomes: valence (positive vs. negative), duration (length of effect), magnitude (strength of effect), and quality (type of effect). The article concludes with a discussion of implications for HRD practitioners and researchers.

A statistical method for the identification and aggregation of regional linguistic variation

This paper introduces a method for the analysis of regional linguistic variation. The method identifies individual and common patterns of spatial clustering in a set of linguistic variables measured over a set of locations based on a combination of three statistical techniques: spatial autocorrelation, factor analysis, and cluster analysis. To demonstrate how to apply this method, it is used to analyze regional variation in the values of 40 continuously measured, high-frequency lexical alternation variables in a 26-million-word corpus of letters to the editor representing 206 cities from across the United States.

Statnote 11: the two-factor analysis of variance

Experiments combining different groups or factors are a powerful method of investigation in applied microbiology. ANOVA enables not only the effect of individual factors to be estimated but also their interactions; information which cannot be obtained readily when factors are investigated separately. In addition, combining different treatments or factors in a single experiment is more efficient and often reduces the number of replications required to estimate treatment effects adequately. Because of the treatment combinations used in a factorial experiment, the degrees of freedom (DF) of the error term in the ANOVA is a more important indicator of the ‘power’ of the experiment than simply the number of replicates. A good method is to ensure, where possible, that sufficient replication is present to achieve 15 DF for each error term of the ANOVA. Finally, in a factorial experiment, it is important to define the design of the experiment in detail because this determines the appropriate type of ANOVA. We will discuss some of the common variations of factorial ANOVA in future statnotes. If there is doubt about which ANOVA to use, the researcher should seek advice from a statistician with experience of research in applied microbiology.

Statnote 13: a more complex analysis of variance incorporating a 'repeated measures' factor

Experiments combining different groups or factors and which use ANOVA are a powerful method of investigation in applied microbiology. ANOVA enables not only the effect of individual factors to be estimated but also their interactions; information which cannot be obtained readily when factors are investigated separately. In addition, combining different treatments or factors in a single experiment is more efficient and often reduces the sample size required to estimate treatment effects adequately. Because of the treatment combinations used in a factorial experiment, the degrees of freedom (DF) of the error term in the ANOVA is a more important indicator of the ‘power’ of the experiment than the number of replicates. A good method is to ensure, where possible, that sufficient replication is present to achieve 15 DF for the error term of the ANOVA testing effects of particular interest. Finally, it is important to always consider the design of the experiment because this determines the appropriate ANOVA to use. Hence, it is necessary to be able to identify the different forms of ANOVA appropriate to different experimental designs and to recognise when a design is a split-plot or incorporates a repeated measure. If there is any doubt about which ANOVA to use in a specific circumstance, the researcher should seek advice from a statistician with experience of research in applied microbiology.