Randomized, placebo-controlled, double-blind trial of Swedish snus for smoking reduction and cessation

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies suggest that smokeless tobacco in the form of Swedish snus has been used by many smokers in Scandinavia to quit smoking, but the efficacy of snus has so far not been evaluated in controlled clinical trials.</p> <p>Methods</p> <p>We conducted a randomized, double-blind, placebo-controlled, clinical trial aimed at assessing the efficacy of snus to help adult cigarette smokers in Serbia to substantially reduce, and, eventually, completely stop smoking. The study enrolled 319 healthy smokers aged 20-65 years at two occupational health centers in Belgrade, Serbia. Most of them (81%) expressed an interest to quit rather than just reduce their smoking. Study products were used <it>ad libitum </it>throughout the 48-week study period. The main study objective during the first 24 weeks was smoking reduction. The primary end-point was defined as a biologically verified reduction of ≥ 50% in the average number of smoked cigarettes per day during week 21-24 compared to baseline. During week 25-48 participants were actively instructed to stop smoking completely. Outcome measures of biologically verified, complete smoking cessation included 1-week point prevalence rates at clinical visits after 12, 24, 36, and 48 weeks, as well as 4-, 12- and 24-week continued cessation rates at the week 36 and 48 visits.</p> <p>Results</p> <p>At the week 24 visit, the proportion of participants who achieved the protocol definition of a ≥ 50% smoking reduction was similar in the two treatment groups. However, the proportion that reported more extreme reductions (≥ 75%) was statistically significantly higher in the snus group than in the placebo group (p < 0.01). The results for biologically verified complete cessation suggested that participants in the snus group were more likely to quit smoking completely than the controls; the odds ratio (snus versus placebo) for the protocol estimates of cessation varied between 1.9 to 3.4, but these ratios were of borderline significance with p-values ranging from 0.04-0.10. Snus was well tolerated and only 2/158 (1.3%) participants in the snus group discontinued treatment due to an adverse event (in both cases unrelated to snus).</p> <p>Conclusions</p> <p>Swedish snus could promote smoking cessation among smokers in Serbia, that is, in a cultural setting without traditional use of oral, smokeless tobacco.</p> <p>Trial registration</p> <p>www.clinicaltrials.gov, identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00601042">NCT00601042</a></p

Ocean circulation drifts in multi-millennial climate simulations: the role of salinity corrections and climate feedbacks

Low-resolution, complex general circulation models (GCMs) are valuable tools for studying the Earth system on multi-millennial timescales. However, slowly evolving salinity drifts can cause large shifts in climatic and oceanic regimes over thousands of years. We test two different schemes for neutralising unforced salinity drifts in the FAMOUS GCM: surface flux correction and volumetric flux correction. Although both methods successfully maintain a steady global mean salinity, local drifts and subsequent feedbacks promote cooling (≈ 4 °C over 6000 years) and freshening (≈ 2 psu over 6000 years) in the North Atlantic Ocean, and gradual warming (≈ 0.2 °C per millennium) and salinification (≈ 0.15 psu per millennium) in the North Pacific Ocean. Changes in the surface density in these regions affect the meridional overturning circulation (MOC), such that, after several millennia, the Atlantic MOC (AMOC) is in a collapsed state, and there is a strong, deep Pacific MOC (PMOC). Furthermore, the AMOC exhibits a period of metastability, which is only identifiable with run lengths in excess of 1500 years. We also compare simulations with two different land surface schemes, demonstrating that small biases in the surface climate may cause regional salinity drifts and significant shifts in the MOC (weakening of the AMOC and the initiation then invigoration of PMOC), even when the global hydrological cycle has been forcibly closed. Although there is no specific precursor to the simulated AMOC collapse, the northwest North Pacific and northeast North Atlantic are important areas that should be closely monitored for trends arising from such biases

​A malversação do reconhecimento no trabalho docente precarizado e intensificado

Le but de cet article est d'analyser les paradoxes, les impasses et les (im)possibilités de reconnaissance dans le/du travail du professeur d'université. Des résumés de trois recherches sont présentés ici: la première recherche a analysé le travail, la subjectivité et la santé dans une université en expansion; la deuxième a abordé le travail intensifié de l'enseignant dans un programme d'excellence de troisième cycle; et la troisième a étudié le travail précaire du tuteur dans l'enseignement à distance. Les analyses s'articulent autour des axes suivants: le travail, la sociabilité et la subjectivité; le détournement de la reconnaissance, de la souffrance et de la maladie; l’intensification et la précarité du travail. On conclut que la précarisation-intensification du travail engendre une unité contradictoire de plaisir-souffrance dans laquelle la reconnaissance est mise en suspens, lorsqu'elle n'est pas annulé ou frauduleux. La souffrance et les processus pathogènes prévalent aussi silencieux qu’insidieux. Mots-clés: travail de professeur d'université; détournement de reconnaissance; souffrance et maladie; Psychodynamique du travail.The purpose of this article is to analyze the paradoxes, the impasses and the (im)possibilities of the recognition in/of the work of the university professor. Summaries of three surveys are presented: the first analyzed work, subjectivity and health in an expanding university; another addressed the intensified work of the teacher in a postgraduate program of excellence; and the third studied the precarious work of the tutor in distance education. The analyses are articulated around the following axes: work, sociability and subjectivity; malpractice of the recognition, suffering and illness; intensification and precariousness of work. It is concluded that the precariousness-intensification of work engenders a contradictory unity of pleasure-suffering in which recognition is placed in suspense, when not de-effected or falsified. Prevails the suffering and pathogenic processes that are both silenced and insidious. Keywords: university professor's work; malpractice of the recognition; suffering and illness; Psychodynamics of Work.El objetivo de este artículo es analizar las paradojas, los impasses y las (im)posibilidades del reconocimiento en el/del trabajo del profesor universitario. Se presentan las síntesis de tres investigaciones: la primera analizó el trabajo, la subjetividad y la salud en una universidad en expansión; la otra abordó el trabajo intensificado del profesor en un programa de post-grado de excelencia; y la tercera estudió el trabajo precarizado del tutor en la educación a distancia. Los análisis se articulan en torno a los siguientes ejes: trabajo, sociabilidad y subjetividad; malversación del reconocimiento, sufrimiento y enfermedad; intensificación y precarización del trabajo. Se concluye que la precarización-intensificación del trabajo genera una unidad contradictoria de placer-sufrimiento en la cual el reconocimiento es puesto como suspendido, cuando no es des-efectivo o defraudado. Prevalecen el sufrimiento y los procesos patogénicos tan silenciados como insidiosos. Palabras-clave: trabajo del profesor universitario; malversación del reconocimiento; sufrimiento y enfermedad; Psicodinámica del Trabajo.O objetivo deste artigo é analisar os paradoxos, os impasses e as (im)possibilidades do reconhecimento no/do trabalho do professor universitário. São apresentadas sínteses de três pesquisas: a primeira analisou trabalho, subjetividade e saúde em uma universidade em expansão; outra abordou o trabalho intensificado do professor em um programa de pós-graduação de excelência; e a terceira estudou o trabalho precarizado do tutor na educação a distância. As análises se articulam em torno dos seguintes eixos: trabalho, sociabilidade e subjetividade; malversação do reconhecimento, sofrimento e adoecimento; intensificação e precarização do trabalho. Conclui-se que a precarização-intensificação do trabalho engendra uma unidade contraditória de prazer-sofrimento na qual o reconhecimento é colocado em suspenso, quando não des-efetivado ou fraudado. Prevalecem o sofrimento e os processos patogênicos tão silenciados quanto insidiosos. Palavras-chave: trabalho do professor universitário; malversação do reconhecimento; sofrimento e adoecimento; Psicodinâmica do Trabalho

Reduced Bone Mineralization in Adolescent Survivors of Malignant Bone Tumors: Comparison of Quantitative Ultrasound and Dual-Energy X-Ray Absorptiometry

To assess bone mineralization in adolescents with bone tumors at remission using quantitative digital ultrasound (QUS) and dual-energy x-ray absorptiometry (DEXA), and to compare the bone mineralization values obtained by both methods. METHODS: Patients studied were 36 adolescents (21 boys, 15 girls) who had completed treatment of a bone tumor at the University Hospital of the University of Navarra (Pamplona, Spain). QUS was performed at the distal metaphysis of the proximal phalanxes of the last four fingers of the nondominant hand. A DBM Sonic 1200 Ultrasound densitometer was used. DEXA measurements were made at the lumbar spine (vertebrae L1-L4) using the Hologic QDR 4500 W device. Calcium and vitamin D daily intake and grade of physical activity were recorded. RESULTS: Mean age at bone mineralization determination was 19.11 years. Disease-free survival was 4.97 years. Decreased bone mineralization was observed by both methods. Bone mineralization absolute values measured by QUS and DEXA were significantly correlated. The sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of QUS for predicting osteopenia were 36.4%, 80.0%, 66.7%, 44.4%, and 74.1%, respectively. Daily vitamin D intake was below the recommended dietary allowances. CONCLUSIONS: Adolescents in remission from bone tumors have low bone mineralization determined by DEXA or QUS

Bone Mineral Density and Bone Metabolism In Children Treated for Bone Sarcomas

In adolescent bone sarcoma patients, bone mass acquisition is potentially compromised at a time in which it should be at a maximum. To evaluate the problem we measured bone mineral density (BMD) and serum markers of bone formation and resorption in a series of pediatric patients with bone tumors. BMD was measured by dual-energy x-ray absorptiometry, at clinical remission, for lumbar spine and the neck of the femur in 38 osteosarcoma and 25 Ewing's sarcoma patients. Mean age was 20.65 and 19.13 y respectively. Serum markers of bone metabolism were: OC, PICP, ICTP, 25-OH vit D and 1,25-(OH)(2) vit D, IGF-I, IGFBP-3 and intact PTH. Serum was sampled throughout anti-tumoral treatments and follow-up. We analyzed 85 samples from 59 osteosarcoma patients and 54 samples from 36 Ewing's sarcoma patients. Patients had decreased lumbar and femoral BMD. The decrease was more pronounced in pubertal patients compared with those who had completed pubertal development at the time of disease diagnosis. Multivariate analysis indicated that sex, age, weight and BMI were significant in lumbar BMD depletion. Weight and BMI were significant in femoral BMD depletion. Serum markers of bone formation (PICP and OC) and resorption (ICTP) were, throughout, lower than reference values. Significant alterations in other markers were also observed. Up to a third of osteosarcoma and Ewing's sarcoma patients in clinical remission had some degree of BMD deficit. The corresponding increased risk of pathologic bone fractures constitutes a reduction in future quality o

Analysis of Polymorphisms of the Vitamin D Receptor, Estrogen Receptor, and Collagen Iα1 Genes and Their Relationship With Height in Children With Bone Cancer

The authors' objectives were to compare height at diagnosis of children with bone tumors with that of Spanish reference children; to analyze the frequency of the genotypes for the polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIalpha1) genes in patients and in healthy controls; and to test the relationship between the genetic markers and height. PATIENTS AND METHODS: Height and weight at diagnosis were measured in 58 osteosarcoma and 36 Ewing sarcoma patients and compared with standards published for Spanish reference children according to sex and age. For the molecular analysis, genetic polymorphisms of the VDR (Fok I, Apa I, and TaqI), ER (Pvu II and XbaI), and COLIalpha1 (Msc I) genes were characterized in 72 osteosarcoma and 53 Ewing sarcomas and in a group of 143 healthy matched children. RESULTS: Osteosarcoma and Ewing sarcoma patients were significantly taller than Spanish reference children. Osteosarcoma patients showed a significantly higher frequency of the Ff genotype for the Fok I polymorphism (VDR gene) than the control group. The odds ratio for this genotype was 1.78, with an increased relative risk of 78% for heterozygous Ff carriers. Among Ewing sarcoma patients, this same genotype was significantly associated with lower height than homozygotes (FF or ff). CONCLUSIONS: Children with bone cancer are significantly taller than the reference population, which may be influenced by the genotype for the Fok I polymorphism of the VDR gene

RELACIÓN ENTRE FACTORES DE RIESGO DEL CONSUMO DE DROGAS Y PRONÓSTICO ACADÉMICO EN ESTUDIANTES DE NUEVO INGRESO EN LA CARRERA DE ENFERMERÍA EN DOS UNIVERSIDADES LATINOAMERICANAS

 The objective of this study was to compare risk factors associated with licit and illicit drugs use and academic prognosis of first year nursing students from two Latin American universities.  The research design was non-experimental, transectional, and correlational-descriptive. Two questionnaires were used: Academic Prognosis Test (APT) by Bennett and Drug Use Screening Inventory (DUSI) test by OEA/CICAD.  The outcome indicates that the academic prognosis was different in both countries, and the most relevant risk factors associated with licit and illicit drugs abuse were recreation and free time use in students from both universities. It was found that abstract reasoning ability is a drug consumption protective factor. It is concluded that it is relevant to create preventive programs, based on psychosocial skills that make students develop thinking abilities and decision making as a life skill that helps them to withstand pressures from peer groups.El objetivo del estudio fue comparar los factores de riesgo del consumo de drogas y  el  pronóstico académico en estudiantes de nuevo ingreso de la carrera de enfermería en dos universidades latinoamericanas.  El diseño fue no experimental, de tipo transeccional, descriptivo-correlacional, se aplicaron dos instrumentos: el Test de Pronóstico académico (APT) de Bennett y la prueba DUSI (Drug Use Screening Inventory) de la OEA/CICAD.  Los hallazgos evidenciaron que el pronóstico académico fue diferente en ambos países, y los factores de riesgo mas relevantes para el consumo de drogas fueron la recreación y el uso del tiempo libre para estudiantes de ambas universidades. Se encontró que la presencia de un razonamiento abstracto es un factor protector del consumo de drogas, se concluye en la necesidad de crear programas preventivos, basados en el enfoque de habilidades psicosociales, que desarrollen en los estudiantes la capacidad de pensar y tomar decisiones como una habilidad para la vida que les permitiría resistir las presiones de grupos propias de la edad

Static Charges in the Low-Energy Theory of the S-Duality Twist

We continue the study of the low-energy limit of N=4 super Yang-Mills theory compactified on a circle with S-duality and R-symmetry twists that preserve N=6 supersymmetry in 2+1D. We introduce external static supersymmetric quark and anti-quark sources into the theory and calculate the Witten Index of the resulting Hilbert space of ground states on a torus. Using these results we compute the action of simple Wilson loops on the Hilbert space of ground states without sources. In some cases we find disagreement between our results for the Wilson loop eigenvalues and previous conjectures about a connection with Chern-Simons theory.Comment: 73 pages, two paragraphs added, one to the introduction and one to the discussio

Structural Analysis and Development of Notum Fragment Screening Hits

The Wnt signaling suppressor Notum is a promising target for osteoporosis, Alzheimer's disease, and colorectal cancers. To develop novel Notum inhibitors, we used an X-ray crystallographic fragment screen with the Diamond-SGC Poised Library (DSPL) and identified 59 fragment hits from the analysis of 768 data sets. Fifty-eight of the hits were found bound at the enzyme catalytic pocket with potencies ranging from 0.5 to >1000 μM. Analysis of the fragments' diverse binding modes, enzymatic inhibitory activities, and chemical properties led to the selection of six hits for optimization, and five of these resulted in improved Notum inhibitory potencies. One hit, 1-phenyl-1,2,3-triazole 7, and its related cluster members, have shown promising lead-like properties. These became the focus of our fragment development activities, resulting in compound 7d with IC50 0.0067 μM. The large number of Notum fragment structures and their initial optimization provided an important basis for further Notum inhibitor development