Cannabis dependence in Swiss adolescents: An exploration of the role of anxiety, coping styles and psychosocial difficulties

This naturalistic cross-sectional study explores how and to what extent cannabis dependence was associated with intrapersonal aspects (anxiety, coping styles) and interpersonal aspects of adolescent functioning (school status, family relationships, peer relationships, social life). A convenience sample of 110 adolescents (aged 12 to 19) was recruited and subdivided into two groups (38 with a cannabis dependence and 72 nondependent) according to DSM-IV-TR criteria for cannabis dependence. Participants completed the State-Trait Anxiety Inventory (STAI-Y), the Coping Across Situations Questionnaire (CASQ), and the Adolescent Drug Abuse Diagnosis (ADAD) interview investigating psychosocial and interpersonal problems in an adolescent's life. Factors associated with cannabis dependence were explored with logistic regression analyses. The results indicated that severity of problems in social life and peer relationships (OR = 1.68, 95% CI = 1.21 - 2.33) and avoidantcoping (OR = 4.22, 95% CI = 1.01 - 17.73) were the only discriminatory factors for cannabis dependence. This model correctly classified 84.5% of the adolescents. These findings are partially consistent with the "self-medication hypothesis" and underlined the importance of peer relationships and dysfunctional coping strategies in cannabis dependence in adolescence. Limitations of the study and implications for clinical work with adolescents are discussed.

Determinants of Decentralization within the Firm: Some Empirical Evidence from Spanish Small and Medium- Sized Enterprise

This paper examines empirically the determinants of decentralization of decision- making in the firm for small and medium-sized enterprises (SMEs) that tend to be highly centralized. By decentralization of decisions we mean the delegation of decision rights from the owner or manager to the plant supervisor or even to floor workers. Our findings show that the allocation of authority to basic workers or a team of workers depends on firm characteristics such as firm size, the use of internal networks or the number of workplaces, and workers characteristics, in particular, the composition of the laborforce in terms of education and seniority and whether or not workers receive pay incentives. External factors such as the intensity of competition and the firm s export intensity are also important determinants of the allocation of authority.

Identification of potential small molecule binding pockets on Rho family GTPases

Rho GTPases are conformational switches that control a wide variety of signaling pathways critical for eukaryotic cell development and proliferation. They represent attractive targets for drug design as their aberrant function and deregulated activity is associated with many human diseases including cancer. Extensive high-resolution structures (.100) and recent mutagenesis studies have laid the foundation for the design of new structure-based chemotherapeutic strategies. Although the inhibition of Rho signaling with drug-like compounds is an active area of current research, very little attention has been devoted to directly inhibiting Rho by targeting potential allosteric non-nucleotide binding sites. By avoiding the nucleotide binding site, compounds may minimize the potential for undesirable off-target interactions with other ubiquitous GTP and ATP binding proteins. Here we describe the application of molecular dynamics simulations, principal component analysis, sequence conservation analysis, and ensemble small-molecule fragment mapping to provide an extensive mapping of potential small-molecule binding pockets on Rho family members. Characterized sites include novel pockets in the vicinity of the conformationaly responsive switch regions as well as distal sites that appear to be related to the conformations of the nucleotide binding region. Furthermore the use of accelerated molecular dynamics simulation, an advanced sampling method that extends the accessible time-scale of conventional simulations, is found to enhance the characterization of novel binding sites when conformational changes are important for the protein mechanism.

Food security, food safety and small farmers

Some of the elements that characterize the globalization of food and agriculture are industrialization and intensification of agriculture and liberalization of agricultural markets, that favours elongation of the food chain and homogenization of food habits (nutrition transition), among other impacts. As a result, the probability of food contamination has increased with the distance and the number of “hands" that may contact the food (critical points); the nutritional quality of food has been reduced because of increased transport and longer periods of time from collection to consumption; and the number of food-related diseases due to changes in eating patterns has increased. In this context, there exist different agencies and regulations intended to ensure food safety at different levels, e.g. at the international level, Codex Alimentarius develops standards and regulations for the marketing of food in a global market. Although governments determine the legal framework, the food industry manages the safety of their products, and thus, develops its own standards for their marketing, such as the Good Agricultural Practices (GAP) programs. The participation of the private sector in the creation of regulatory standards strengthens the free trade of food products, favouring mostly large agribusiness companies. These standards are in most cases unattainable for small producers and food safety regulations are favouring removal of the peasantry and increase concentration and control in the food system by industrial actors. Particularly women, who traditionally have been in charge of the artisanal transformation process, can be more affected by these norms than men. In this project I am analysing the impcact of food safety norms over small farms, based on the case of artisanal production made by women in Spain.

Improving the organisation and commercialisation of small coffee and cocoa producers in the Northern Amazon Region of Ecuador

Coffee and cocoa represent the main sources of income for small farmers in the Northern Amazon Region of Ecuador. The provinces of Orellana and Sucumbios, as border areas, have benefited from investments made by many public and private institutions. Many of the projects carried out in the area have been aimed at energising the production of coffee and cocoa, strengthening the producers’ associations and providing commercialisation infrastructure. Improving the quality of life of this population threatened by poverty and high migration flows mainly from Colombia is a significant challenge. This paper presents research highlighting the importance of associative commercialisation to raising income from coffee and cocoa. The research draws on primary information obtained during field work, and from official information from the Ministry of Agriculture. The study presents an overview of current organisational structures, initiatives of associative commercialisation, stockpiling of infrastructure and ownership regimes, as well as estimates for both ‘robusta’ coffee and national cocoa production and income. The analysis of the main constraints presents different alternatives for the implementation of public land policies. These policies are aimed at mitigating the problems associated with the organisational structure of the producers, with processes of commercialisation and with environmental aspects, among others.

Assessment of terrestrial small mammals and a record of the critically endangered shrew Crocidura wimmeri in Banco National Park (Cote d'Ivoire)

This study investigated the small mammal community of the periurban Banco National Park (34 km(2)), Abidjan, Cote d'Ivoire, using identical numbers of Sherman and Longworth traps. We aimed to determine the diversity and distribution of rodents and shrews in three different habitats: primary forest, secondary forest and swamp. Using 5014 trap-nights, 91 individuals were captured that comprised seven rodent and four shrew species. The trapping success was significantly different for each species, i.e., the Longworth traps captured more soricids (31/36 shrews), whereas the Sherman traps captured more murids (37/55 mice). The most frequent species was Praomys cf. rostratus, followed by Crocidura buettikoferi, Hybomys trivirgatus and Crocidura jouvenetae. Indices of species richness (S) and diversity (H') were greatest in primary forest, followed by secondary forest and swamp. - Several expected species, such as Crocidura obscurior, were not found, whereas we captured four specimens of the critically endangered (IUCN 2012) Wimmer's shrew Crocidura wimmeri, a species that has vanished from its type locality, Adiopodoume. Therefore, Banco National Park represents an important sanctuary, not only for plants, birds and primates, but also for other small forest vertebrates.

Small and long non-coding RNAs in cardiac homeostasis and regeneration

Cardiovascular diseases and in particular heart failure are major causes of morbidity and mortality in the Western world. Recently, the notion of promoting cardiac regeneration as a means to replace lost cardiomyocytes in the damaged heart has engendered considerable research interest. These studies envisage the utilization of both endogenous and exogenous cellular populations, which undergo highly specialized cell fate transitions to promote cardiomyocyte replenishment. Such transitions are under the control of regenerative gene regulatory networks, which are enacted by the integrated execution of specific transcriptional programs. In this context, it is emerging that the non-coding portion of the genome is dynamically transcribed generating thousands of regulatory small and long non-coding RNAs, which are central orchestrators of these networks. In this review, we discuss more particularly the biological roles of two classes of regulatory non-coding RNAs, i.e. microRNAs and long non-coding RNAs, with a particular emphasis on their known and putative roles in cardiac homeostasis and regeneration. Indeed, manipulating non-coding RNA-mediated regulatory networks could provide keys to unlock the dormant potential of the mammalian heart to regenerate. This should ultimately improve the effectiveness of current regenerative strategies and discover new avenues for repair. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice

The involvement of μ-opioid receptors in different behavioral responses elicited by nicotine was explored by using μ-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of μ-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that μ-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.

A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: a randomized trial.

BACKGROUND: The dose intensity of chemotherapy can be increased to the highest possible level by early administration of multiple and sequential high-dose cycles supported by transfusion with peripheral blood progenitor cells (PBPCs). A randomized trial was performed to test the impact of such dose intensification on the long-term survival of patients with small cell lung cancer (SCLC). METHODS: Patients who had limited or extensive SCLC with no more than two metastatic sites were randomly assigned to high-dose (High, n = 69) or standard-dose (Std, n = 71) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE). High-ICE cycles were supported by transfusion with PBPCs that were collected after two cycles of treatment with epidoxorubicin at 150 mg/m(2), paclitaxel at 175 mg/m(2), and filgrastim. The primary outcome was 3-year survival. Comparisons between response rates and toxic effects within subgroups (limited or extensive disease, liver metastases or no liver metastases, Eastern Cooperative Oncology Group performance status of 0 or 1, normal or abnormal lactate dehydrogenase levels) were also performed. RESULTS: Median relative dose intensity in the High-ICE arm was 293% (range = 174%-392%) of that in the Std-ICE arm. The 3-year survival rates were 18% (95% confidence interval [CI] = 10% to 29%) and 19% (95% CI = 11% to 30%) in the High-ICE and Std-ICE arms, respectively. No differences were observed between the High-ICE and Std-ICE arms in overall response (n = 54 [78%, 95% CI = 67% to 87%] and n = 48 [68%, 95% CI = 55% to 78%], respectively) or complete response (n = 27 [39%, 95% CI = 28% to 52%] and n = 24 [34%, 95% CI = 23% to 46%], respectively). Subgroup analyses showed no benefit for any outcome from High-ICE treatment. Hematologic toxicity was substantial in the Std-ICE arm (grade > or = 3 neutropenia, n = 49 [70%]; anemia, n = 17 [25%]; thrombopenia, n = 17 [25%]), and three patients (4%) died from toxicity. High-ICE treatment was predictably associated with severe myelosuppression, and five patients (8%) died from toxicity. CONCLUSIONS: The long-term outcome of SCLC was not improved by raising the dose intensity of ICE chemotherapy by threefold.

ASTRAL Score Predicts 5-Year Dependence and Mortality in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The ASTRAL score was externally validated showing remarkable consistency on 3-month outcome prognosis in patients with acute ischemic stroke. The present study aimed to evaluate ASTRAL score's prognostic accuracy to predict 5-year outcome. METHODS: All consecutive patients with acute ischemic stroke registered in the Athens Stroke Registry between January 1, 1998, and December 31, 2010, were included. Patients were excluded if admitted >24 hours after symptom onset or if any ASTRAL score component was missing. End points were 5-year unfavorable functional outcome, defined as modified Rankin Scale 3 to 6, and 5-year mortality. For each outcome, the area under the receiver operating characteristics curve was calculated; also, a multivariate Cox proportional hazards analysis was performed to investigate whether the ASTRAL score was an independent predictor of outcome. The Kaplan-Meier product limit method was used to estimate the probability of 5-year survival for each ASTRAL score quartile. RESULTS: The area under the receiver operating characteristics curve of the score to predict 5-year unfavorable functional outcome was 0.89, 95% confidence interval 0.88 to 0.91. In multivariate Cox proportional hazards analysis, the ASTRAL score was independently associated with 5-year unfavorable functional outcome (hazard ratio, 1.09; 95% confidence interval, 1.08-1.10). The area under the receiver operating characteristics curve for the ASTRAL score's discriminatory power to predict 5-year mortality was 0.81 (95% confidence interval, 0.78-0.83). In multivariate analysis, the ASTRAL score was independently associated with 5-year mortality (hazard ratio, 1.09, 95% confidence interval, 1.08-1.10). During the 5-year follow-up, the probability of survival was significantly lower with increasing ASTRAL score quartiles (log-rank test <0.001). CONCLUSIONS: The ASTRAL score reliably predicts 5-year functional outcome and mortality in patients with acute ischemic stroke.

Acceptance of an intended smoking ban in an alcohol dependence clinic.

Alcohol treatment professionals are often reluctant to address tobacco dependence in their patients or to implement smoke-free policies in inpatient treatment programs, fearing, among others, non-adherence to alcohol treatment. The aim of the present study was to evaluate the acceptance of an intended smoking ban in a specialized hospital for alcohol withdrawal. Fifteen of 54 patients reported that they would not begin or quit alcohol treatment if smoking were banned in the clinic, but only five would not begin or quit if nicotine replacement were available. The present study indicates that a non-smoking policy would be feasible in a Swiss alcohol clinic, without jeopardizing alcohol treatment adherence.

Angle Parking on Iowa's Low Volume Primary Extentions in Small Towns, January 2003

On-street parking has been considered problematic by engineers for many years. In fact, numerous studies have concluded that diagonal or angle parking in particular is potentially more of a safety concern than parallel or no parking at all. It is a common position of many states, including Iowa, to discourage or completely prohibit angle parking on primary road extensions in urban areas. However, with the acceptance of “context sensitive design” and traffic calming techniques, policies for on-street parking are receiving re -consideration in many agencies including the FHWA. This study was undertaken to analyze operational and safety histories in the state of Iowa where various types of on-street parking have existed for many years, concentrating in particular on smaller communities. Specifically of interest was a comparison of diagonal parking locations to other types with regard to related crash histories. If possible, it was intended to develop guidelines to assist Iowa Department of Transportation designers in the consideration of parking requirements for road improvements through small communities. In this regard, several criteria were analyzed to determine possible contribution to crash history including road width, clearance to parked vehicles, traffic volumes, community population, and length of parking area. None of these factors, with the possible exception of population, displayed a clearly definable relationship to crash history. However, when average crash rates for various parking types were compared for non-intersection crashes, differences in rates between areas with diagonal parking and those with parallel parking were almost negligible. In fact, those observed rates were less than sample locations with no parking at all. These results seem to indicate that indeed there may exist no compelling justification for blanket prohibition of angle parking along Iowa’s primary extensions in all urban areas. Rather, a case-by-case investigation with each project design of the most applicable parking type would seem appropriate in smaller communities.

Separation of small metabolites and lipids in spectra from biopsies by diffusion-weighted HR-MAS NMR: a feasibility study.

High Resolution Magic Angle Spinning (HR-MAS) NMR allows metabolic characterization of biopsies. HR-MAS spectra from tissues of most organs show strong lipid contributions that are overlapping metabolite regions, which hamper metabolite estimation. Metabolite quantification and analysis would benefit from a separation of lipids and small metabolites. Generally, a relaxation filter is used to reduce lipid contributions. However, the strong relaxation filter required to eliminate most of the lipids also reduces the signals for small metabolites. The aim of our study was therefore to investigate different diffusion editing techniques in order to employ diffusion differences for separating lipid and small metabolite contributions in the spectra from different organs for unbiased metabonomic analysis. Thus, 1D and 2D diffusion measurements were performed, and pure lipid spectra that were obtained at strong diffusion weighting (DW) were subtracted from those obtained at low DW, which include both small metabolites and lipids. This subtraction yielded almost lipid free small metabolite spectra from muscle tissue. Further improved separation was obtained by combining a 1D diffusion sequence with a T2-filter, with the subtraction method eliminating residual lipids from the spectra. Similar results obtained for biopsies of different organs suggest that this method is applicable in various tissue types. The elimination of lipids from HR-MAS spectra and the resulting less biased assessment of small metabolites have potential to remove ambiguities in the interpretation of metabonomic results. This is demonstrated in a reproducibility study on biopsies from human muscle.

Transcriptional and functional profiles of voltage-gated Na(+) channels in injured and non-injured DRG neurons in the SNI model of neuropathic pain.

Changes in expression and function of voltage-gated sodium channels (VGSC) in dorsal root ganglion (DRG) neurons may play a major role in the genesis of peripheral hyperexcitability that occurs in neuropathic pain. We present here the first description of changes induced by spared nerve injury (SNI) to Na(v)1 mRNA levels and tetrodotoxin-sensitive and -resistant (TTX-S/TTX-R) Na(+) currents in injured and adjacent non-injured small DRG neurons. VGSC transcripts were down-regulated in injured neurons except for Na(v)1.3, which increased, while they were either unchanged or increased in non-injured neurons. TTX-R current densities were reduced in injured neurons and the voltage dependence of steady-state inactivation for TTX-R was positively shifted in injured and non-injured neurons. TTX-S current densities were not affected by SNI, while the rate of recovery from inactivation was accelerated in injured neurons. Our results describe altered neuronal electrogenesis following SNI that is likely induced by a complex regulation of VGSCs.