Strategic planning as the intentional production of a “Trading Zone”

For a long period of time there has been a kind of mirroring between the development of decision making models in Political science and the concepts and paradigms used in Planning theory. The dialogue has been interrupted when the "Garbage Can" model was proposed by Choen, March and Olsen in 1972: a model that emphasized the irreducible complexity of the policy processes. The article reconstructs this relationship and its evolution showing the influence of decision-making models on planning theory, and showing the difficulties of managing complexity for planners. The paper holds that interpreting planning processes through the lens of the "Trading zone" concept proposed by Peter Galison in the field of history of science could be an interesting way of dealing with the extreme complexity of contemporary planning problems. The conclusion is that the use of the Trading Zone concept is very promising to solve some dilemmas of planning theory and that it is particularly useful if we employ it in the growing area of strategic spatial planning

Impact of vital signs screening & clinician prompting on alcohol and tobacco screening and intervention rates: a pre-post intervention comparison

<p>Abstract</p> <p>Background</p> <p>Though screening and intervention for alcohol and tobacco misuse are effective, primary care screening and intervention rates remain low. Previous studies have increased intervention rates using vital signs screening for tobacco misuse and clinician prompts for screen-positive patients for both alcohol and tobacco misuse. This pilot study's aims were: (1) To determine the feasibility of combined vital signs screening for tobacco and alcohol misuse, (2) To assess the impact of vital signs screening on alcohol and tobacco screening and intervention rates, and (3) To assess the additional impact of tobacco assessment prompts on intervention rates.</p> <p>Methods</p> <p>In five outpatient practices, nurses measuring vital signs were trained to routinely ask a single tobacco question, a prescreening question that identified current drinkers, and the single alcohol screening question for current drinkers. After 4-8 weeks, clinicians were trained in tobacco intervention and nurses were trained to give tobacco abusers a tobacco questionnaire which also served as a clinician intervention prompt. Screening and intervention rates were measured using patient exit interviews (n = 622) at baseline, during the "screening only" period, and during the tobacco prompting phase. Changes in screening and intervention rates were compared using chi square analyses and test of linear trends. Clinic staff were interviewed regarding patient and staff acceptability. Logistic regression was used to evaluate the impact of nurse screening on clinician intervention, the impact of alcohol intervention on concurrent tobacco intervention, and the impact of tobacco intervention on concurrent alcohol intervention.</p> <p>Results</p> <p>Alcohol and tobacco screening rates and alcohol intervention rates increased after implementing vital signs screening (p < .05). During the tobacco prompting phase, clinician intervention rates increased significantly for both alcohol (12.4%, p < .001) and tobacco (47.4%, p = .042). Screening by nurses was associated with clinician advice to reduce alcohol use (OR 13.1; 95% CI 6.2-27.6) and tobacco use (OR 2.6; 95% CI 1.3-5.2). Acceptability was high with nurses and patients.</p> <p>Conclusions</p> <p>Vital signs screening can be incorporated in primary care and increases alcohol screening and intervention rates. Tobacco assessment prompts increase both alcohol and tobacco interventions. These simple interventions show promise for dissemination in primary care settings.</p

Axis I comorbidity in adolescent inpatients referred for treatment of substance use disorders

<p>Abstract</p> <p>Background</p> <p>To assess comorbid DSM-IV-TR Axis I disorders in adolescent inpatients referred for treatment of substance use disorders.</p> <p>Methods</p> <p>151 patients (mean age 16.95 years, SD = 1.76; range 13 - 22) were consecutively assessed with the Composite International Diagnostic Interview (CIDI) and standardized clinical questionnaires to assess mental disorders, symptom distress, psychosocial variables and detailed aspects of drug use. A consecutively referred subgroup of these 151 patients consisting of 65 underage patients (mean age 16.12, SD = 1.10; range 13 - 17) was additionally assessed with the modules for attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) using The Schedule for Affective Disorders and Schizophrenia for school-aged children (K-SADS-PL).</p> <p>Results</p> <p>128 (84.8%) of the 151 patients were dependent on at least one substance, the remaining patients fulfilled diagnostic criteria for abuse only. 40.5% of the participants fulfilled criteria for at least one comorbid present Axis I disorder other than substance use disorders (67.7% in the subgroup additionally interviewed with the K-SADS-PL). High prevalences of present mood disorder (19.2%), somatoform disorders (9.3%), and anxiety disorders (22.5%) were found. The 37 female participants showed a significantly higher risk for lifetime comorbid disorders; the gender difference was significantly pronounced for anxiety and somatoform disorders. Data from the underage subgroup revealed a high prevalence for present CD (41.5%). 33% of the 106 patients (total group) who were within the mandatory school age had not attended school for at least a two-month period prior to admission. In addition, 51.4% had been temporarily expelled from school at least once.</p> <p>Conclusions</p> <p>The present data validates previous findings of high psychiatric comorbidity in adolescent patients with substance use disorders. The high rates of school refusal and conduct disorder indicate the severity of psychosocial impairment.</p

HMGA1 Induces Intestinal Polyposis in Transgenic Mice and Drives Tumor Progression and Stem Cell Properties in Colon Cancer Cells

Although metastatic colon cancer is a leading cause of cancer death worldwide, the molecular mechanisms that enable colon cancer cells to metastasize remain unclear. Emerging evidence suggests that metastatic cells develop by usurping transcriptional networks from embryonic stem (ES) cells to facilitate an epithelial-mesenchymal transition (EMT), invasion, and metastatic progression. Previous studies identified HMGA1 as a key transcription factor enriched in ES cells, colon cancer, and other aggressive tumors, although its role in these settings is poorly understood.To determine how HMGA1 functions in metastatic colon cancer, we manipulated HMGA1 expression in transgenic mice and colon cancer cells. We discovered that HMGA1 drives proliferative changes, aberrant crypt formation, and intestinal polyposis in transgenic mice. In colon cancer cell lines from poorly differentiated, metastatic tumors, knock-down of HMGA1 blocks anchorage-independent cell growth, migration, invasion, xenograft tumorigenesis and three-dimensional colonosphere formation. Inhibiting HMGA1 expression blocks tumorigenesis at limiting dilutions, consistent with depletion of tumor-initiator cells in the knock-down cells. Knock-down of HMGA1 also inhibits metastatic progression to the liver in vivo. In metastatic colon cancer cells, HMGA1 induces expression of Twist1, a gene involved in embryogenesis, EMT, and tumor progression, while HMGA1 represses E-cadherin, a gene that is down-regulated during EMT and metastatic progression. In addition, HMGA1 is among the most enriched genes in colon cancer compared to normal mucosa.Our findings demonstrate for the first time that HMGA1 drives proliferative changes and polyp formation in the intestines of transgenic mice and induces metastatic progression and stem-like properties in colon cancer cells. These findings indicate that HMGA1 is a key regulator, both in metastatic progression and in the maintenance of a stem-like state. Our results also suggest that HMGA1 or downstream pathways could be rational therapeutic targets in metastatic, poorly differentiated colon cancer

Caspase Dependent Programmed Cell Death in Developing Embryos: A Potential Target for Therapeutic Intervention against Pathogenic Nematodes

Pathogenic nematodes currently infect billions of people around the world and pose serious challenges to the economic welfare and public health in most developing countries. At present, limitations of existing therapies warrant identification of new anti-parasitic drugs/drug targets to effectively treat and control neglected tropical diseases [NTD] caused by nematode pathogens. The current gold standard for measuring/screening drug effectiveness against most helminth parasites is in-vitro assessment of motility of parasites/larvae and larval development assays which fails to provide any conclusive idea about the precise mechanism of death of parasitic worms or their larval stages. Given the huge load of parasites or their larval stages in an infected host, a compound which shows promise in in-vitro/motility screening assays but induces necrotic death in parasites/larvae will be of limited use, as it may elicit severe inflammatory response in infected hosts. In this context, the present study, which demonstrates induction of apoptotic death in developing embryos of a pathogenic nematode as a potential drug target for the first time, and provides scope for high throughput screening of pharmacological agents for their apoptogenicity against nematode embryos, is a step forward to develop novel anti-parasitic measures to challenge NTD caused by nematode pathogens

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts