Tumour biology, metastatic sites and taxanes sensitivity as determinants of eribulin mesylate efficacy in breast cancer: results from the ERIBEX retrospective, international, multicenter study.

BACKGROUND: Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting. METHODS: Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data. RESULTS: Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia. CONCLUSION: EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors.

The International ADHD in Substance Use Disorders Prevalence (IASP) study: background, methods and study population

Attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized comorbid condition in subjects with substance use disorders (SUDs). This paper describes the methods and study population of the International ADHD in Substance Use Disorders Prevalence (IASP) study. Objectives of the IASP are to determine the prevalence of ADHD in adult treatment seeking patients with SUD in different countries and SUD populations, determine the reliability and validity of the Adult ADHD Self-report Scale V 1.1 (ASRS) as ADHD screening instrument in SUD populations, investigate the comorbidity profile of SUD patients with and without ADHD, compare risk factors and protective factors in SUD patients with and without a comorbid diagnosis of ADHD, and increase our knowledge about the relationship between ADHD and the onset and course of SUD. In this cross-sectional, multi-centre two stage study, subjects were screened for ADHD with the ASRS, diagnosed with the Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID), and evaluated for SUD, major depression, bipolar disorder, anti social personality disorder and borderline personality disorder. Three thousand five hundred and fifty-eight subjects from 10 countries were included. Of these 40.9% screened positive for ADHD. This is the largest international study on this population evaluating ADHD and comorbid disorders.

The Butler wears Prada. A Hungarian case-study based on the analysis of the uniform and hotel industry from the point of sustainability

What is the connection between the hotel and fashion industry? The authors aim to answer this question approaching from different aspects. It can be stated that both of these industries are harmful for the environment from the point of sustainability. On the other hand there is a common solution from the viewpoint of sustainability: the uniforms and the primary materials, which are used during the production, such as the man-made and natural fibres. In our research the authors introduce the main problems which are related to the fashion industry, especially focusing on producing fibres from the viewpoint of sustainability. We introduce the solution for the fashion industry based on the literature and also present the emerging problems and solutions of the hotel industry based on the best practices. As a part of it, we are introducing the best practices from the hotel industry, where environmentally friendly uniforms are used. Finally, as a primary research part of our paper, we interpret the results of a Hungarian case-study.

Studio pancreatic cystic follow-up, an international collaboration (PACYFIC study). Valutazione prospettica della sorveglianza delle cisti pancreatiche basato sulla consensus Europea sui tumori cistici del pancreas.

Introduzione Nel 2014 è stato proposto un protocollo di studio riguardante la sorveglianza delle lesioni cistiche del pancreas (intese come IPMN) e denominato PACYFIC Study. Obiettivi Obiettivo primario era di stabilire l’impatto di un programma di sorveglianza in termini di pazienti arruolati e pazienti con indicazione chirurgica. Obiettivi secondari erano: 1) stabilire l’impatto dei fattori demografici, clinici, radiologici e della strategia di sorveglianza sull’indicazione chirurgica, sulla capacità individuare le lesioni maligne, sulla sopravvivenza. Materiali e Metodi Lo studio su cui si è basata la raccolta dei dati è uno studio di tipo prospettico, di coorte, multicentrico, internazionale. Lo studio ha incluso gli individui con una IPMN, di nuova o pregressa diagnosi, che giustifichi una sorveglianza o il trattamento chirurgico. I dati clinici, demografici, radiologici e chirurgici sono stati raccolti in un database prospettico. Le variabili discrete sono state espresse come frequenza e percentuale. Le continue come medie e deviazioni standard o mediane e range interquartile (IQR). Per l’analisi statistica sono stati utilizzati il test di Fischer, il test del Chi quadro, il test di Spearman, il test di Student. L’analisi multivariata è stata eseguita utilizzando la regressione logistica espressa come Odds Ratio e intervallo di confidenza al 95 %. Per la sopravvivenza è stato utilizzato il metodo di Kaplan-Meier. L’analisi multivariata sulle sopravvivenze è stata eseguita mediante la regressione di Cox. Risultati Il protocollo di sorveglianza ha permesso l'arruolamento di 516 pazienti. 53 pazienti hanno raggiunto l'indicazione chirurgica. La sopravvivenza globale della coorte è stata di 326.8± 9.1 mesi. I fattori predittivi la sopravvivenza sono risultati età (OR 1.07, P-value<0.001), sesso (OR 1.82, P-value=0.006), ittero, noduli murali (OR 4.84, P-value=0.018 e OR 2.19, P-value=0.016), chirurgia (OR 0.46, P-value 0.038). Conclusioni L'introduzione del protocollo di sorveglianza ha portato ad un aumento di identificazione di lesioni e ha avuto impatto sulla sopravvivenza

Environment and Health in Children Day Care Centres (ENVIRH) - Study Rationale and Protocol

Background: Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. Methods --- study design: This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children’s respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. Results: In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children’s health. A building ventilation model will also be developed. Discussion: This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC.

E-Governance and Citizen Information : The Generalitat of Catalonia in the International Context. Research report (synthesis document)

Aquest estudi té com a objectiu principal analitzar les transformacions que s'esdevenen al voltant de la incorporació d'innovacions tecnològiques de l'entorn de les TIC en els processos d'atenció al ciutadà per part de les administracions públiques. Les transformacions que hem analitzat tenen a veure amb tres dimensions que hem considerat bàsiques. D'una banda, ens hem centrat en els canvis que es produeixen en la forma en què els ciutadans (com a principals, tot i que no únics, usuaris) i l'administració es relacionen entre sí. De l'altra hem analitzat les transformacions que s'esdevenen en el funcionament intern i en la pròpia organització de l'administració arran de les transformacions dels canals de comunicació amb els usuaris. Per últim, hem considerat els canvis en la forma de gestionar (dissenyar, planificar, organitzar i dur a terme) el canvi i la innovació, tenint en compte especialment els rols dels diferents actors (no només públics) que hi participen. La recerca es recolza en un ampli estudi empíric sobre la Generalitat de Catalunya i en un estudi compartiu internacional sobre el Quebec, Emillia-Romagna i Escòcia.

Global alcohol exposure estimates by country, territory and region for 2005--a contribution to the Comparative Risk Assessment for the 2010 Global Burden of Disease Study.

AIMS: This study aimed to estimate the prevalence of life-time abstainers, former drinkers and current drinkers, adult per-capita consumption of alcohol and pattern of drinking scores, by country and Global Burden of Disease region for 2005, and to forecast these indicators for 2010. DESIGN: Statistical modelling based on survey data and routine statistics. SETTING AND PARTICIPANTS: A total of 241 countries and territories. MEASUREMENTS: Per-capita consumption data were obtained with the help of the World Health Organization's Global Information System on Alcohol and Health. Drinking status data were obtained from Gender, Alcohol and Culture: An International Study, the STEPwise approach to Surveillance study, the World Health Survey/Multi-Country Study and other surveys. Consumption and drinking status data were triangulated to estimate alcohol consumption across multiple categories. FINDINGS: In 2005 adult per-capita annual consumption of alcohol was 6.1 litres, with 1.7 litres stemming from unrecorded consumption; 17.1 litres of alcohol were consumed per drinker, 45.8% of all adults were life-time abstainers, 13.6% were former drinkers and 40.6% were current drinkers. Life-time abstention was most prevalent in North Africa/Middle East and South Asia. Eastern Europe and Southern sub-Saharan Africa had the most detrimental pattern of drinking scores, while drinkers in Europe (Eastern and Central) and sub-Saharan Africa (Southern and West) consumed the most alcohol. CONCLUSIONS: Just over 40% of the world's adult population consumes alcohol and the average consumption per drinker is 17.1 litres per year. However, the prevalence of abstention, level of alcohol consumption and patterns of drinking vary widely across regions of the world.

Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group.

New evidence shows that older adults need more dietary protein than do younger adults to support good health, promote recovery from illness, and maintain functionality. Older people need to make up for age-related changes in protein metabolism, such as high splanchnic extraction and declining anabolic responses to ingested protein. They also need more protein to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging. With the goal of developing updated, evidence-based recommendations for optimal protein intake by older people, the European Union Geriatric Medicine Society (EUGMS), in cooperation with other scientific organizations, appointed an international study group to review dietary protein needs with aging (PROT-AGE Study Group). To help older people (>65 years) maintain and regain lean body mass and function, the PROT-AGE study group recommends average daily intake at least in the range of 1.0 to 1.2 g protein per kilogram of body weight per day. Both endurance- and resistance-type exercises are recommended at individualized levels that are safe and tolerated, and higher protein intake (ie, ≥1.2 g/kg body weight/d) is advised for those who are exercising and otherwise active. Most older adults who have acute or chronic diseases need even more dietary protein (ie, 1.2-1.5 g/kg body weight/d). Older people with severe kidney disease (ie, estimated GFR <30 mL/min/1.73m(2)), but who are not on dialysis, are an exception to this rule; these individuals may need to limit protein intake. Protein quality, timing of ingestion, and intake of other nutritional supplements may be relevant, but evidence is not yet sufficient to support specific recommendations. Older people are vulnerable to losses in physical function capacity, and such losses predict loss of independence, falls, and even mortality. Thus, future studies aimed at pinpointing optimal protein intake in specific populations of older people need to include measures of physical function.

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in seven unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits, thereby interfering with integrin maturation and/or function. Our study extends knowledge of GT and the pathophysiology of an integrin.

A comparison of indices of glucose metabolism in five black populations: data from modeling the epidemiologic transition study (METS).

BACKGROUND: Globally, Africans and African Americans experience a disproportionate burden of type 2 diabetes, compared to other race and ethnic groups. The aim of the study was to examine the association of plasma glucose with indices of glucose metabolism in young adults of African origin from 5 different countries. METHODS: We identified participants from the Modeling the Epidemiologic Transition Study, an international study of weight change and cardiovascular disease (CVD) risk in five populations of African origin: USA (US), Jamaica, Ghana, South Africa, and Seychelles. For the current study, we included 667 participants (34.8 ± 6.3 years), with measures of plasma glucose, insulin, leptin, and adiponectin, as well as moderate and vigorous physical activity (MVPA, minutes/day [min/day]), daily sedentary time (min/day), anthropometrics, and body composition. RESULTS: Among the 282 men, body mass index (BMI) ranged from 22.1 to 29.6 kg/m(2) in men and from 25.8 to 34.8 kg/m(2) in 385 women. MVPA ranged from 26.2 to 47.1 min/day in men, and from 14.3 to 27.3 min/day in women and correlated with adiposity (BMI, waist size, and % body fat) only among US males after controlling for age. Plasma glucose ranged from 4.6 ± 0.8 mmol/L in the South African men to 5.8 mmol/L US men, while the overall prevalence for diabetes was very low, except in the US men and women (6.7 and 12 %, respectively). Using multivariate linear regression, glucose was associated with BMI, age, sex, smoking hypertension, daily sedentary time but not daily MVPA. CONCLUSION: Obesity, metabolic risk, and other potential determinants vary significantly between populations at differing stages of the epidemiologic transition, requiring tailored public health policies to address local population characteristics.

Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study.

PURPOSE: The MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation. METHODS: Survival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens. RESULTS: After a median follow-up of 9.5 years, 10-year OS rates in the bolus/infusional fluorouracil plus leucovorin (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX4) arms were 67.1% versus 71.7% (hazard ratio [HR], 0.85; P = .043) in the whole population, 79.5% versus 78.4% for stage II (HR, 1.00; P = .980), and 59.0% versus 67.1% for stage III (HR, 0.80; P = .016) disease. Ninety-five patients (9.4%) had MMR-deficient (dMMR) tumors, and 94 (10.4%) had BRAF mutation. BRAF mutation was not prognostic for OS (P = .965), but dMMR was an independent prognostic factor (HR, 2.02; 95% CI, 1.15 to 3.55; P = .014). HRs for DFS and OS benefit in the FOLFOX4 arm were 0.48 (95% CI, 0.20 to 1.12) and 0.41 (95% CI, 0.16 to 1.07), respectively, in patients with stage II to III dMMR and 0.50 (95% CI, 0.25 to 1.00) and 0.66 (95% CI, 0.31 to 1.42), respectively, in those with BRAF mutation. CONCLUSION: The OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with dMMR or BRAF mutation.

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in 7 unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits thereby interfering with integrin maturation and/or function. Our study extends knowledge of Glanzmann thrombasthenia and the pathophysiology of an integrin. This article is protected by copyright. All rights reserved.

Learning about Self Far From Home: A Pre-service Teacher’s Intercultural Development During an International Program

Preparing teachers to effectively teach culturally diverse students, teacher educators advocate for the use of cross-cultural field experiences, including international study abroad programs. This paper reports on a qualitative case study of two pre-service teachers’ intercultural development during a semester-long teacher education study abroad program in London, England. Findings indicate that international experiences provide a catalyst to move pre-service teachers forward in their intercultural development. Implications include the need for multicultural teacher educators to take a developmental approach to pre-service teacher education informed by theories of intercultural development and cultural learning developed within intercultural communications.

Na 1 Nachlass Max Horkheimer, 690 - Materialien zu Forschungsprojekten über Antisemitismus u.a. (p. IX 157 - IX 163.1-9)

"Beitrag des Instituts für Sozialforschung zu dem Forschungsprojekt über Autorität" (3.1.1951). Typoskript, 5 Blatt; "Reactions to the Antisemitic Incidents in January 1960. A Pilot Study in Frankfurt am Main. Summary of Procedure and Results" (1960). Typoskript, 6 Blatt (= Alt.Sig. IX 234.13 a); "Proposal for International Study of Anti-Semitism" (1960):; 1. American Jewish Committee: Luncheon Meeting, May 25, 1960, Typoskript, 2 Blatt; 2. American Jewish Committee, Institute of Human Relations: "The JDA Agencies and Germany" (17.5.1960). Als Typoskript vervielfältigt, 32 Blatt; Exzerpte aus Werken über Antisemitismus, Literaturlisten (etwa 1933-46):; 1. Everett R. Clinchy, Typoskript, 1 Blatt; 2. Paul K. Hatt, Typoskript, 3 Blatt; 3. John Moffat Mecklin, Typoskript, 3 Blatt; 4. Conrad Henry Moehlman, Typoskript, 4 Blatt; 5. Maurice Samuel, Typoskript, 5 Blatt; 6. Milton Steinberg, Typoskript, 2 Blatt; 7. "General Literature on Antisemitism", Liste, Typoskript mit handschriftlichen Ergänzungen, 1 Blatt; 8. "Bibliography" zum Judentum, 15 Blatt; 9. Literaturliste, handschriftliche Notizen, 9 Blatt; 10. Literaturliste, eigenhändige Notizen von Max Horkheimer, 1 Blatt; 11. Literaturliste, 1 Blatt; 12. Zitate zum Judentum aus Zeitschriften, 1 Blatt; Memorandum zum Antisemitismus (1944-48):; 1. S. Andhil Fineberg: "Notes on 'A Mask for Privilege' by Carey McWilliams", als Typoskript vervielfältigt, 4 Blatt; Carey McWilliams: "Memorandum" (8.5.1948), Typoskript, 3 Blatt; Lawrence Bloomgarden und S.A. Fineberg: "In Reply to Carey McWilliams Memorandum of May 8th", Typoskript, 3 Blatt; 2. Rundbriefe der American Jewish Sociological Society, 1944, als Typoskript vervielfältigt, 4 Blatt; 3. Bericht über einen Vortrag von Wladimir Eliasberg über Antisemitismus, Typoskript, 1 Blatt; Abschriften und Übersetzungen aus Zeitungsartikeln über Antisemitismus (1939-43):; 1. "A Note on Anti-Semitism", aus: The New Statesman and Nation (13.3.1939), Typoskript, 7 Blatt; 2. Abschriften aus deutschen und englischen Zeitungen, 1939, Typoskript, 1 Blatt; 3. "A Homility of the Bishop of Cremona" (Übersetzung aus: Osservatore Romano) 1939. Typoskript, 18 Blatt; Veröffentlichungen über Antisemitismus, Vorurteil, Demagogie (1941-63):; 1. Earl Raab und Seymour M. Lipset: "Prejudice and Society", Freedom Pamphlet Anti-Defamation League of B'nai B'rith (New York 1963), 48 Seiten; 2. Committee on Education, Training and Research in Race Relations of the University of Chicago: Bulletin, Nr. 1, 30.6.1948, 55. Seiten; 3. Solomon Andhil Fineberg: "Checkmate for Rabble-Rousers. What to Do When the Demagogue Comes to Town", Sonderdruck aus Commentary, Vol. 2, 1946 und eine Broschüre, 20 Seiten; 4. Kurt Lewin: "A new Approach to Old Problems", aus: Congress Week, 19.1.1945, 2 Blatt; 5. Eric A. Johnston: "Intolerance", New York, 11.1.1945, Heft, 8 Blatt; 6. Philip Wylie: "Memorandum on Anti-Semitism", aus: American Mercury, Januar 1945, 5 Blatt; 7. S.I. Hayakawa: "Race and Words", aus: Common Sense, Juli 1943, 3 Blatt; 8. David Riesman: "The Politics of Persecution". Als Typoskript vervielfältigt, 21 Blatt; 9. James P. Gifford, Frank D. Schroth, Maximilian Moss, Edward A. Richards, Samuel J. Levinson, Thomas G. Grace: "Anti-Semitism. It's Causes and Cures", New York, 1941, 30 Seiten;