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Collaborations between the National Association of Professors of Middle Level Education (NAPOMLE) and European League for Middle Level Education (ELMLE) can be mutually beneficial. This article reflects on NAPOMLE's past experiences with our global affiliate ELMLE and promotes future partnerships expanding our commitment to supporting the development of middle schools and middle level leaders. We advocate a global approach to preparing and empowering the next generation of middle school leaders.

Objectives To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment. Methods Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999–2008), B (2009–2014) and C (2015–2018). Retention, remission and response rates were assessed at 6, 12 and 24 months. Results In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months. Conclusion Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years. [ABSTRACT FROM AUTHOR]

This article will describe seven shamanic figures located in four caves, in artwork created during the Paleolithic period. Each shaman is described and interpreted as a single figure and then interpreted in the context of figures in proximate art panels. Hunters represented by animals are considered to be fully human and are assigned average consciousness. Then shamans in a trance are in a more advanced state of consciousness. The spirits shamans encounter while in a trance are considered to be in a yet higher state of consciousness. The authors identify the ritual each shaman is performing and suggest, as a convention, that the shamans-artists put a bird head on shamans performing rituals associated with the spirit world and a bison head when performing rituals associated with the natural world. The authors identify fifteen conventions that provide structure to the artwork and underpin the meaning of the shamanic worldview. The integrating discussion arises out of the general model the authors have described in earlier articles to interpret the artwork. Six glossary notes, placed at the end of the article, are offered for places in the text where the discussion should be understood within a larger context, and which serve to deepen the reader's understanding. [ABSTRACT FROM AUTHOR]

Bioenergy from crops is expected to make a considerable contribution to climate change mitigation. However, bioenergy is not necessarily carbon neutral because emissions of CO2, N2O and CH4 during crop production may reduce or completely counterbalance CO2 savings of the substituted fossil fuels. These greenhouse gases ( GHGs) need to be included into the carbon footprint calculation of different bioenergy crops under a range of soil conditions and management practices. This review compiles existing knowledge on agronomic and environmental constraints and GHG balances of the major European bioenergy crops, although it focuses on dedicated perennial crops such as M iscanthus and short rotation coppice species. Such second-generation crops account for only 3% of the current European bioenergy production, but field data suggest they emit 40% to >99% less N2O than conventional annual crops. This is a result of lower fertilizer requirements as well as a higher N-use efficiency, due to effective N-recycling. Perennial energy crops have the potential to sequester additional carbon in soil biomass if established on former cropland (0.44 Mg soil C ha−1 yr−1 for poplar and willow and 0.66 Mg soil C ha−1 yr−1 for M iscanthus). However, there was no positive or even negative effects on the C balance if energy crops are established on former grassland. Increased bioenergy production may also result in direct and indirect land-use changes with potential high C losses when native vegetation is converted to annual crops. Although dedicated perennial energy crops have a high potential to improve the GHG balance of bioenergy production, several agronomic and economic constraints still have to be overcome. [ABSTRACT FROM AUTHOR]

A new lineage is discovered within the Botryosphaeriaceae (Ascomycetes, Dothideomycetes, incertae sedis). Consistent with current practice of providing generic names for independent lineages, this lineage is described as Endomelanconiopsis gen. nov., with the anamorphic species E. endophytica sp. nov. and E. microspora comb. nov. (= Endomelanconium microsporum). Endomelanconiopsis is characterized by eustromatic conidiomata and holoblastically produced, brown, nonapiculate, unicellular conidia, each with a longitudinal germ slit. Phylogenetic analysis of partial sequences of LSU, ITS and translation elongation factor 1 alpha (tef1) indicate that E. endophytica is sister of E. microspora and that they are nested within the Botryosphaeriaceae. However because there is no support for the "backbone" of the Botryosphaeriacae we are not able to see the interrelationships among the many genera in the family. Neither species is known to have a teleomorph. Endomelanconiopsis differs from Endomelanconium because conidia of the type species of Endomelanconium, E. pini, are papillate at the base, conidiogenous cells proliferate sympodially and the pycnidial wall is thinner; we postulate that the teleomorph of E. pini as yet unknown is an inoperculate discomycete. Endomelanconiopsis endophytica was isolated as an endophyte from healthy leaves of Theobroma cacao (cacao,. Malvaceae) and Heisteria concinna (Elythroplaceae) in Panama. Endomelanconiopsis microspora was isolated from soil in Europe. [ABSTRACT FROM AUTHOR]

This study of the annual reports of the Illinois Central Railroad (IC) from the 1850s supports a conclusion that the statements, as to form and content, were developed to serve the needs of two classes of investors and to inform the general community of the activities of the company. The need to report to the public as to the success of the company's role in its "social contract" to develop the state required details of a demographic nature, which were provided by the land commissioner. Operating results provided evidence of the ability to service the debts held by European investors and to inform British venture capitalists of the extent of the company's operations. This communication with the distant capital providers was a new development in financial reporting as the capital-intensive railroads experienced management and ownership separation on a scale not seen before. In summary, the IC provided annual reports more detailed and informative than those of other corporations of the period because of a need to provide European investors with evidence of management's activities. [ABSTRACT FROM AUTHOR]

The article explores the epidemiology of esophageal cancer in Great Britain and other European countries. European countries exhibit low rates of esophageal cancer, with an exception to males living in France. The rates of esophageal cancer have been increasing during the previous 40 years in both men and women in Great Britain. Nutrition and the interaction of nutrition with tobacco and alcohol should be the focus of studies of esophageal cancer in Europe.

Recent literature has suggested that a key stakeholder may he able to shift the balance of bargaining power during a joint venture negotiation, and thus change the outcome of the process. This paper explores the role of central and eastern European transitional governments as key stakeholders, and how they influence international joint venture negotiations. This role is described and analyzed by examining eight dyads of western European and central/eastern European enterprises that have recently negotiated agreements. The findings suggest that transitional governments as key stakeholders intervene at different stages of the negotiation process, have both direct and indirect influences on the process, and that they can change the balance of power in the negotiations, sometimes to the detriment of their own state-owned enterprise. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We aimed to assess the association of oral health (OH), dental care (DC) and mouthwash with upper-aerodigestive tract (UADT) cancer risk, and to examine the extent that enzymes involved in the metabolism of alcohol modify the effect of mouthwash. Materials and methods: The study included 1963 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1993 controls. Subjects were interviewed about their oral health and dental care behaviors (which were converted to scores of OH and DC respectively), as well as smoking, alcohol drinking, diet, occupations, medical conditions and socio-economic status. Blood samples were taken for genetic analyses. Mouthwash use was analyzed in relation to the presence of polymorphisms of alcohol-metabolizing genes known to be associated with UADT. Adjusted odds ratios (ORs) and 95%-confidence intervals [CI] were estimated with multiple logistic regression models adjusting for multiple confounders. Results: Fully adjusted ORs of low versus high scores of DC and OH were 2.36[CI=1.51–3.67] and 2.22[CI=1.45–3.41], respectively, for all UADT sites combined. The OR for frequent use of mouthwash use (3 or more times/day) was 3.23[CI=1.68–6.19]. The OR for the rare variant ADH7 (coding for fast ethanol metabolism) was lower in mouthwash-users (OR=0.53[CI=0.35–0.81]) as compared to never-users (OR=0.97[CI=0.73–1.29]) indicating effect modification (p heterogeneity =0.065) while no relevant differences were observed between users and non-users for the variant alleles of ADH1B, ADH1C or ALDH2. Conclusions: Poor OH and DC seem to be independent risk factors for UADT because corresponding risk estimates remain substantially elevated after detailed adjustment for multiple confounders. Whether mouthwash use may entail some risk through the alcohol content in most formulations on the market remains to be fully clarified. [Copyright &y& Elsevier]

Abstract: The aim of this study was to determine the association of hormone levels with the occurrence of musculoskeletal pain. Men ages 40 to 79years were recruited from population registers in 8 European centres. Subjects were asked to complete a postal questionnaire, which enquired about lifestyle and the occurrence of musculoskeletal pain over the past month. Total testosterone (T), oestradiol (E2), luteinising hormone (LH), and follicle-stimulating hormone (FSH) were assayed from a fasting blood sample. The association between pain status and hormone levels was assessed using multinomial logistic regression with results expressed as relative risk ratios (RRR) and 95% confidence intervals (CI). A total of 3206 men had complete data on pain status. Of these, 8.7% reported chronic widespread pain (CWP), whereas 50% had some pain although not CWP and were classified as having some pain. T and E2 were not associated with musculoskeletal pain, whereas significant differences in LH and FSH levels were found between pain groups. After adjustment for age and other possible confounders, the association between pain status and both LH and FSH persisted. Compared with those in the lowest tertile of LH, those in the highest tertile were more likely to report some pain (vs no pain, RRR=1.28; 95% CI 1.09 to 1.50) and also CWP (vs no pain, RRR=1.51; 95% CI 1.10 to 2.07). Similar results were found for FSH. Gonadotrophins, but not sex steroid hormone levels, are associated with musculoskeletal pain in men. Higher levels of gonadotrophins but not androgens were significantly associated with musculoskeletal pain in men. Alterations in hypothalamic–pituitary–testicular feedback mechanisms may play a role in the onset of chronic widespread pain. [Copyright &y& Elsevier]

• Microwave pyrolysis of olive pomace was investigated. • Optimal processing conditions were determined to be 200 W for 180 s. • Energy requirement of 3.6 kJ/g pyrolysed 80% of OP and yielded 30% bio-oil. • Microwave power influenced textural and adsorption properties of bio-chars. • Bio-oils contained a high abundance of acetic acid. Olive pomace is a widely available agro-industrial waste residue in Europe that has the potential to contribute towards a circular, low carbon bio-economy. This study demonstrated, for the first time, the ability to successfully pyrolyse olive pomace with microwaves for the production of bio-char and bio-oil. It was found that the energy requirement needed to pyrolyse up to 80% of the olive pomace was as low as 3.6 kJ/g and bio-oil yields up to 30% were produced. Microwave power did not influence the overall yields or the chemical composition of the obtained bio-oils, but did alter the textural properties of the generated bio-chars and their ability to remove methylene blue dye. Optimum processing conditions were found to be within the 3.6 kJ/g energy requirement with a microwave power of 200 W and processing time of 180 sec. These conditions produced a bio-oil fraction containing mainly acetic acid (71.9%) and a bio-char with a surface area of 392.3 m2/g, micropore volume of 0.15 cm3/g and a methylene blue removal efficiency of 40 qMB mg/g. The results acquired from this study reveal the superiority of microwave heating in a pyrolysis system and highlight a novel and prospective route for added value recovery from natural waste resources like olive pomace. [ABSTRACT FROM AUTHOR]

Objective: Because 66/68 joint counts are not always performed in routine care, we aimed to determine which of the modified 28-joint disease activity index for psoriatic arthritis (DAPSA28) or 28-joint disease activity score with C-reactive protein (DAS28-CRP) should be preferred for monitoring disease activity in psoriatic arthritis (PsA) when the original DAPSA (66/68 joints) is not available., Methods: Prospectively collected real-world data of European bionaive patients with PsA initiating a first tumor necrosis factor inhibitor were pooled. Remission and response status were evaluated at 6 months by remission (DAPSA ≤ 4, DAPSA28 ≤ 4, and DAS28-CRP < 2.6), response (75% improvement for DAPSA and DAPSA28), and combined EULAR good/moderate responses for DAS28-CRP. Logistic regression analyses on multiple imputed data were used to identify baseline predictors., Results: Remission and response cohorts included 3,159 and 1,866 patients, respectively. The 6-month proportions achieving remission/response were DAPSA (27%/44%), DAPSA28 (28%/44%), and DAS28-CRP (59%/80%). Of 14 possible baseline predictors, 11 predicted both DAPSA and DAPSA28 remission (8 of which also predicted their response, indicated by "*"): longer disease duration*, male sex*, and higher CRP* were positive, whereas older age*, higher body mass index*, patient fatigue*, and global, physician global, health assessment questionnaire score*, and tender and swollen* joint counts were negative predictors. Eight and five of these predicted DAS28-CRP remission and response, respectively., Conclusion: In patients with PsA, DAPSA28 should be preferred over DAS28-CRP as a substitute for DAPSA when 66/68 joint counts are not available because of the large overlap in remission and response status and in predictors between DAPSA and DAPSA28., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Head and neck cancer (HNC) incidence is on the rise, often diagnosed at late stage and associated with poor prognoses. Risk prediction tools have a potential role in prevention and early detection., Methods: The IARC-ARCAGE European case-control study was used as the model development dataset. A clinical HNC risk prediction model using behavioral and demographic predictors was developed via multivariable logistic regression analyses. The model was then externally validated in the UK Biobank cohort. Model performance was tested using discrimination and calibration metrics., Results: 1926 HNC cases and 2043 controls were used for the development of the model. The development dataset model including sociodemographic, smoking, and alcohol variables had moderate discrimination, with an area under curve (AUC) value of 0.75 (95% CI, 0.74-0.77); the calibration slope (0.75) and tests were suggestive of good calibration. 384 616 UK Biobank participants (with 1177 HNC cases) were available for external validation of the model. Upon external validation, the model had an AUC of 0.62 (95% CI, 0.61-0.64)., Conclusion: We developed and externally validated a HNC risk prediction model using the ARCAGE and UK Biobank studies, respectively. This model had moderate performance in the development population and acceptable performance in the validation dataset. Demographics and risk behaviors are strong predictors of HNC, and this model may be a helpful tool in primary dental care settings to promote prevention and determine recall intervals for dental examination. Future addition of HPV serology or genetic factors could further enhance individual risk prediction., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Objectives: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe., Methods: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders)., Results: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates., Conclusion: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status., Competing Interests: Competing interests: SNC: Speaker fees BMS and GE, Research grant from Novartis (paid to the employer). SHR: Research grant from Novartis (paid to the employer). MO: Speaker and/or consultancy fees from AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB. Research grants from AbbVie, BMS, Merck, Novartis and UCB. MP: Research grant from Novartis (paid to the employer). Speaker fees: Sandoz. Brigitte Michelsen: Consulting fees from Novartis. Research grant from Novartis (paid to employer). KP: Consultancy fees: AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD and Novartis. Catalin Codreanu: Speaker and consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer. Adrian Ciurea: None. Bente Glintborg: Research grants from Pfizer, Abbvie, BMS, Sandoz. MJS: Speaker fees from AbbVie, AstraZeneca, Janssen, Lilly, Medac, Novartis, Pfizer. Ismail Sari: None. ZR: Speaker and consultancy fees from Abbvie, Novartis, Eli Lilly, Pfizer, Janssen, SOBI, Swixx BioPharma, AstraZeneca, Amgen, MSD, Medis, Biogen, Eli Lilly, Sanofi, Lek. BG: Speaker and consultancy fees from Novartis and Nordic-Pharma. GJM: Research grant from GSK. HR: Consulting and/or speaking fees from AbbVie, Celgene, Pfizer, UCB, Viatris. FI: None. Karin Laas: Speakers fees from AbbVie, Johnson and Johnson, Novartis, Pfizer. JKW: Speaker fees from AbbVie, Amgen. Research support from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer. MvdS: Consultant for Novartis, AbbVie, Eli Lilly UCB, Speakers fee: Novartis, UCB, Janssen, Grant/research support: UCB, Janssen, Novartis, Eli Lilly. Sella Aarrestad Provan: Consultancy fees and Research grants from Boehringer Ingelheim. IC: Speaker and/or consultancy fees from BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Novartis, MSD, Pfizer, GSK. JZ: Speakers fees from AbbVie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Sanofi, Astra Zeneca, Sobi. CM: None. MJN: Speaker and/or consultancy fees from AbbVie, Amgen, Eli Lilly, Janssens, Novartis, Pfizer. Research grants from Novartis and Pfizer. AGL: Speaking and/or consulting fees from AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, UCB. Research grant from Novartis. AB: Speaker and/or consultancy fees from AbbVie, Lilly, Janssen and Novartis. YE: None. Katja Perdan Pirkmajer: Speaker and/or consultancy fees from AbbVie, Novartis, MSD, Medis, Eli Lilly, Pfizer, Lek, Janssen and Boehringer Ingelheim. GG: None. GTJ: Speaker fee from Janssen. Research grants (paid to employer) from AbbVie, Pfizer, UCB, Amgen, GSK. A-MH: Grant/research support from MSD. MSC: None. SV: None. DdG: None. TKK: Speaker and/or consultancy fees from AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB and Grünenthal. LO-V: None. IvdH-B: Speaker and/or consultancy fees from AbbVie, UCB, MSD, Novartis, Lilly. Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie, UCB. Fees received for Lectures from BMS, AbbVie, Pfizer, MSD, UCB. MLH: Advisory Board AbbVie (No personal income, paid to institution). Prev. chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. Speaker for Pfizer, Medac, Sandoz (no personal income, institution). Research grants (institution) from AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk. LMO: Research grant from Novartis (paid to the employer)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment., Methods: Prospectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively)., Results: We included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67-70%) and 66% (64-68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi., Conclusion: Two-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as "first-in-class" (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development. We succinctly describe the mechanism of action of most of these FIC drugs and discuss the therapeutic areas covered, as well as the chemical category to which these drugs belong. The 2023 novel drug list also demonstrates an unabated emphasis on polypeptides (recombinant proteins and antibodies), Advanced Therapy Medicinal Products (gene and cell therapies) and RNA therapeutics, including the first-ever approval of a CRISPR-Cas9-based gene-editing cell therapy., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Sipha maydis Passerini (Heteroptera: Aphididae) is a cereal pest with an extensive geographical range that includes countries in Europe, Asia, Africa, and South America. Reports of S. maydis in the United States have been infrequent since it was first detected in California, 2007. Two studies, focused (NW CO) and multistate (OK, TX, NM, CO, UT, WY), were conducted to determine the distribution and host range of S. maydis in the Rocky Mountain and Southern Plains states over a 3-yr period, 2015-2017. In 2015, focused sampling in NW Colorado found S. maydis at 59% of the 37 sites, primarily on wheat. Sipha maydis did not survive extreme winter temperatures from late December 2015 to early January 2016 that ranged from -9.0 to -20.9°C over a 9-d period, which resulted in no aphids detected in 2016. In the multistate study, S. maydis occurred in 14.6% of 96 sites sampled in 2015, 8% of 123 sites in 2016, and 9% of 85 sites in 2017 at wide range of altitudes from 1,359 to 2,645 m. Sipha maydis occurred mainly in NW and SW Colorado and NE New Mexico along with a few sites in NE Colorado, SE Utah, and SE Wyoming. This aphid mainly infested wheat followed by a variety of eight wild grass species. No parasites, predators, sexual morphs, or significant plant damage occurred at the sites. Sipha maydis utilized 14 hosts in the United States including 8 new host records, which expands its host range to 52 plant species worldwide. Sipha maydis may be of concern to wheat, barley, and sorghum production in the United States if its populations continue to increase., (Published by Oxford University Press on behalf of Entomological Society of America 2019.)

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan-Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow-up time of 4.6 years, nearly 50% (n = 586) of patients died. Five-year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09-2.38 (LH) and HR = 2.12, 95% CI 1.35-3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40-5.08 (LH) and HR = 2.16, 95% CI 1.32-3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78-3.79 (LH) and HR = 3.17, 95% CI 2.05-4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC., (© 2018 International Agency for Research on Cancer (IARC/WHO); licensed by UICC.)

In recent years, formal professionalism education, training, and assessment have been introduced to medical schools and accredited residency training programs. Current constructs of medical professionalism characterize it as a multidimensional competency rather than a trait. Medical professionalism is a belief system for organizing and delivering care, in which group members (medical professionals) promise patients and the public that they will self-regulate (ie, ensure that medical professionals live up to standards of competence and ethical values). Physicians who are good professionals have lapses in professionalism. Responses to professional lapses should focus on remediation. Failure of groups of professionals to enforce the standards and values can convey to patients and the public a lack of trustworthiness and thereby undermine the foundation of professionalism, the social contract. The Physician Charter sets forth the 3 fundamental principles and 10 commitments that offer guidance in some of the most challenging situations. One example is illustrated herein and is continued from Part 1 of this two-part series.

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables., (Copyright © 2013 UICC.)

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry., (Copyright © 2011 UICC.)

Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Unlabelled: Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1., (RSNA, 2011)

Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature., (Copyright © 2010 UICC.)

Background: The incidence of cancers of the upper aerodigestive tract (UADT) is increasing throughout the world. To date the increases have been proportionally greatest among young people. Several reports have suggested that they often do not have a history of tobacco smoking or heavy alcohol consumption., Objective: To determine the contribution of lifestyle factors to the etiology of UADT cancers occurring in those aged less than 50 years., Methods: A case-control study was conducted in 10 European countries. Cases were cancers of the oral cavity and pharynx, larynx and esophagus, and hospital or population controls were age and sex matched., Results: There were 356 cases younger than 50 years and 419 controls. Risk was strongly related to current smoking [odds ratio (OR) 5.5 95%; confidence interval (CI) (3.3, 9.2)], and risk increased with number of pack-years smoked. Risk was also related to alcohol consumption for both current (OR 1.8; 0.97, 3.3) and past (OR 3.4; 1.6, 7.4) drinkers, and risk increased with number of drink-years. Persons frequently consuming fruits and vegetables were at significantly reduced risk., Conclusions: Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike.

Introduction: A study was undertaken to test the hypothesis that musculoskeletal pain is associated with low vitamin D levels but the relationship is explained by physical inactivity and/or other putative confounding factors., Methods: Men aged 40-79 years completed a postal questionnaire including a pain assessment and attended a clinical assessment (lifestyle questionnaire, physical performance tests, 25-hydroxyvitamin D3 (25-(OH)D) levels from fasting blood sample). Subjects were classified according to 25-(OH)D levels as 'normal' (> or = 15 ng/ml) or 'low' (< 15 ng/ml). The relationship between pain status and 25-(OH)D levels was assessed using logistic regression. Results are expressed as ORs and 95% CIs., Results: 3075 men of mean (SD) age 60 (11) years were included in the analysis. 1262 (41.0%) subjects were pain-free, 1550 (50.4%) reported 'other pain' that did not satisfy criteria for chronic widespread pain (CWP) and 263 (8.6%) reported CWP. Compared with patients who were pain-free, those with 'other pain' and CWP had lower 25-(OH)D levels (n=239 (18.9%), n=361 (23.3) and n=67 (24.1%), respectively, p<0.05). After adjusting for age, having 'other pain' was associated with a 30% increase in the odds of having low 25-(OH)D while CWP was associated with a 50% increase. These relationships persisted after adjusting for physical activity levels. Adjusting for additional lifestyle factors (body mass index, smoking and alcohol use) and depression attenuated these relationships, although pain remained moderately associated with increased odds of 20% of having low vitamin D levels., Conclusions: These findings have implications at a population level for the long-term health of individuals with musculoskeletal pain.

We evaluated the activity of daptomycin (minimum inhibitory [MIC] and bactericidal [MBC] concentration) against Staphylococcus aureus strains with elevated (2 microg/mL) vancomycin MIC values. A total of 410 contemporary clinical S. aureus isolates (282 from the United States and 128 from Europe) with vancomycin MIC values of 2 microg/mL were tested by reference broth microdilution method. Vancomycin MBC and the presence of vancomycin-heteroresistant population (heterogeneous vancomycin-intermediate S. aureus [hVISA]) were evaluated in 31 randomly selected strains. Overall, 97.3% of isolates were susceptible to daptomycin (MIC(90), 0.5 microg/mL). Daptomycin exhibited potent bactericidal activity with MBC values at the MIC concentration (74.2%) or 1 log(2) dilution above the MIC (25.8%). In contrast, vancomycin MBC was > or = 32 microg/mL in 12.9% of strains tolerance, and 25.8% of strains tested positive for hVISA (AB BIODISK GRD Etest, Solna, Sweden). In conclusion, S. aureus strains with vancomycin MIC of 2 microg/mL showed high rates of hVISA and vancomycin tolerance. Daptomycin retained potent bactericidal activity against S. aureus with decreased susceptibility to vancomycin., (2010 Elsevier Inc. All rights reserved.)

PURPOSE An international phase II study of laromustine (VNP40101M), a sulfonylhydrazine alkylating agent, was conducted in patients age 60 years or older with previously untreated poor-risk acute myeloid leukemia (AML). PATIENTS AND METHODS Laromustine 600 mg/m(2) was administered as a single 60-minute intravenous infusion. Patients were age 70 years or older or 60 years or older with at least one additional risk factor-unfavorable AML karyotype, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2, and/or cardiac, pulmonary, or hepatic comorbidities. Results Eighty-five patients (median age, 72 years; range, 60 to 87 years) were treated. Poor-risk features included age 70 years or older, 78%; adverse karyotype, 47%; PS of 2, 41%; pulmonary disease, 77%; cardiac disease, 73%; and hepatic disease, 3%. Ninety-six percent of patients had at least two risk factors, and 39% had at least four risk factors. The overall response rate (ORR) was 32%, with 20 patients (23%) achieving complete response (CR) and seven (8%) achieving CR with incomplete platelet recovery (CRp). ORR was 20% in patients with adverse cytogenetics; 32% in those age 70 years or older; 32% in those with PS of 2; 32% in patients with baseline pulmonary dysfunction; 34% in patients with baseline cardiac dysfunction; and 27% in 33 patients with at least four risk factors. Twelve (14%) patients died within 30 days of receiving laromustine therapy. Median overall survival was 3.2 months, with a 1-year survival of 21%; the median duration of survival for those who achieved CR/CRp was 12.4 months, with a 1-year survival of 52%. CONCLUSION Laromustine has significant single-agent activity in elderly patients with poor-risk AML. Adverse events are predominantly myelosuppressive or respiratory. Response rates are consistent across a spectrum of poor-risk features.

Introduction: Several important issues for the established association between tobacco smoking and upper aerodigestive tract (UADT) cancer risks include the associations with smoking by cancer subsite, by type of tobacco, and among never alcohol drinkers and the associations with involuntary smoking among nonsmokers. Our aim was to examine these specific issues in a large-scale case-control study in Europe., Methods: Analysis was done on 2,103 UADT squamous cell carcinoma cases and 2,221 controls in the Alcohol-Related Cancers and Genetic Susceptibility in Europe project, a multicenter case-control study in 10 European countries. Unconditional logistic regression was done to obtain odds ratios (OR) and 95% confidence intervals (95% CI)., Results: Compared with never tobacco smoking, current smoking was associated with UADT cancer risks (OR, 6.72; 95% CI, 5.45-8.30 for overall; OR, 5.83; 95% CI, 4.50-7.54 for oral cavity and oropharynx; OR, 12.19; 95% CI, 8.29-17.92 for hypopharynx and larynx; and OR, 4.17; 95% CI, 2.45-7.10 for esophagus). Among never drinkers, dose-response relationships with tobacco smoking pack-years were observed for hypopharyngeal and laryngeal cancers (P(trend) = 0.010) but not for oral cavity and oropharyngeal cancers (P(trend) = 0.282). Among never smokers, ever exposure to involuntary smoking was associated with an increased risk of UADT cancers (OR, 1.60; 95% CI, 1.04-2.46)., Conclusion: Our results corroborate that tobacco smoking may play a stronger role in the development of hypopharyngeal and laryngeal cancers than that of oral cavity and oropharyngeal cancers among never drinkers and that involuntary smoking is an important risk factor for UADT cancers. Public health interventions to reduce involuntary smoking exposure could help reduce UADT cancer incidence.

Objective: To determine whether perturbations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) were associated with the presence of chronic widespread pain (CWP) in men., Methods: The European Male Ageing Study (EMAS) is an 8-center population-based study of men aged 40-79 years recruited from population registers. A questionnaire asked about the presence and duration of musculoskeletal pain, from which subjects reporting CWP were identified. Subjects also had an interviewer-assisted questionnaire: levels of physical activity and mood were assessed, and height and weight were measured. IGF-1 and IGFBP-3 were assayed from a fasting blood sample. Logistic regression models were used to determine the association between IGF measures and CWP. Results were expressed as odds ratios or relative risk ratios., Results: A total of 3206 subjects provided full data. Of those, 1314 (39.0%) reported no pain in the past month and 278 (8.3%) reported pain that satisfied criteria for CWP. IGF-1 concentrations were similar among subjects who reported no pain and those with CWP: 131.5 mg/l and 128.4 mg/l, respectively. This was true also for IGFBP-3 (4.3 and 4.3 mg/l). Obesity was associated with low IGF-1 and a high IGFBP-3/IGF-1 ratio, indicating less bioavailable IGF-1, irrespective of pain status. This relationship persisted after adjustment for comorbidities, depression, smoking, alcohol consumption, and quality of life., Conclusion: Overall CWP was not associated with perturbations in IGF-1 and IGFBP-3 concentrations. Hypofunctioning of the axis was noted among subjects who were obese and this was not specific to CWP. These data suggest that IGF-1 is unlikely to be etiologically important in relation to CWP, although the relationship with growth hormone remains to be elucidated.

There is suggestive, but inconclusive, evidence that dietary factors may affect risk of cancers of the upper aerodigestive tract (UADT). In the context of the alcohol-related cancers and genetic susceptibility in Europe study, we have examined the association of dietary factors with UADT cancer risk. We have analyzed data from 2,304 patients with UADT cancer and 2,227 control subjects recruited in 14 centers in 10 European countries. Dietary data were collected through a semi-quantitative food frequency questionnaire that also assessed preferred temperature of hot beverages. Statistical analyses were conducted through multiple logistic regression controlling for potential confounding variables, including alcohol intake and smoking habits. Consumption of red meat (OR per increasing tertile = 1.14, 95% CI: 1.05-1.25), but not poultry, was significantly associated with increased UADT cancer risk and the association was somewhat stronger for esophageal cancer. Consumption of fruits (OR per increasing tertile = 0.68, 95% CI: 0.62-0.75) and vegetables (OR per increasing tertile = 0.73, 95% CI: 0.66-0.81) as well as of olive oil (OR for above versus below median = 0.78, 95% CI 0.67-0.90) and tea (OR for above versus below median = 0.83, 95% CI 0.69-0.98) were significantly associated with reduced risk of UADT cancer. There was no indication that an increase in tea or coffee temperature was associated with increased risk of UADT overall or cancer of the esophagus; in fact, the association was, if anything, inverse. In conclusion, the results of this large multicentric study indicate that diet plays an important role in the etiology of UADT cancer.

Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend<0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend=0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend=0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend=0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways.

Background: TR-700, the active component of the oxazolidinone prodrug TR-701, has demonstrated potent activity against numerous Gram-positive species. In this study, single-step mutation frequencies, passaging and the activity of TR-700 were tested against a worldwide collection of linezolid-non-susceptible organisms and matched controls., Methods: One hundred and twenty linezolid-non-susceptible and 120 controls matched by genus/species, geographic origin, site of infection and time were susceptibility tested by reference broth microdilution methods. Species of isolates were: Enterococcus faecalis (16 linezolid non-susceptible/16 wild-type strains); Enterococcus faecium (55/55), Staphylococcus aureus (8/8); coagulase-negative staphylococci (at least 7 spp., 40/40) and viridans group streptococci (2 spp., 1/1). 23S rRNA target mutations or cfr genes were detected by PCR and sequencing., Results: Among linezolid-non-susceptible strains, the resistance mechanisms were G2576T (109), cfr (4) and unknown (7), with strains originating from Europe, Far East and North and South America. Most strains were multidrug-resistant and cfr isolates exhibited co-resistance to phenicols, clindamycin, linezolid, pleuromutilins and streptogramin B. TR-700 MIC values, regardless of species, were 4-32-fold lower than those of linezolid. TR-700 MIC results were < or = 4, < or = 8 or < or = 16 mg/L for 88%, 96% and > 99% of linezolid-non-susceptible strains, respectively. Spontaneous single-step mutations were undetected (<1.1 x 10(-9)) and 14 day passaging studies produced modest TR-700 MIC elevations compared with linezolid controls., Conclusions: TR-700 exhibited enhanced activity against linezolid-non-susceptible and wild-type control strains of Gram-positive cocci. A significant number (nearly 90%) of linezolid-non-susceptible strains were inhibited by potentially achievable levels (< or = 4 mg/L) of TR-700. All strains with the emerging cfr-mediated resistance determinant had TR-700 MIC results at < or = 8 mg/L.

Cancers of the upper aerodigestive tract (UADT) include those of the oral cavity, pharynx (other than nasopharynx), larynx, and esophagus. Tobacco smoking and consumption of alcoholic beverages are established causes of UADT cancers, whereas reduced intake of vegetables and fruits are likely causes. The role of genetic predisposition and possible interactions of genetic with exogenous factors, however, have not been adequately studied. Moreover, the role of pattern of smoking and drinking, as well as the exact nature of the implicated dietary variables, has not been clarified. To address these issues, the International Agency for Research on Cancer initiated in 2002 the alcohol-related cancers and genetic susceptibility (ARCAGE) in Europe project, with the participation of 15 centers in 11 European countries. Information and biological data from a total of 2304 cases and 2227 controls have been collected and will be used in a series of analyses. A total of 166 single nucleotide polymorphisms of 76 genes are being studied for genetic associations with UADT cancers. We report here the methodology of the ARCAGE project, main demographic and lifestyle characteristics of the cases and controls, as well as the distribution of cases by histology and subsite. About 80% of cases were males and fewer than 20% of all cases occurred before the age of 50 years. Overall, the most common subsite was larynx, followed by oral cavity, oropharynx, esophagus and hypopharynx. Close to 90% of UADT cancers were squamous cell carcinomas. A clear preponderance of smokers and alcohol drinkers among UADT cases compared with controls was observed.

Increases in prevalence of vancomycin-resistant enterococci (VRE) have been documented globally since its emergence in the 1980s. A SENTRY Antimicrobial Surveillance Program (2003) objective monitored VRE isolates with respect to antimicrobial susceptibility trends, geographic resistance variability, and clonal dissemination. In 2003, VRE isolates from North America (United States and Canada, n = 839, 26 sites) and Europe (n = 56, 10 sites) were susceptibility tested using Clinical and Laboratory Standards Institute (CLSI) reference methodologies. Based on resistance profiles, 155 isolates displayed similar multidrug-resistant (MDR) profiles and were temporally related; these were subsequently submitted for typing by pulsed-field gel electrophoresis (PFGE). Most of the submitted isolates were Enterococcus faecium (91.0%) and Enterococcus faecalis (7.8%). Among VRE, the VanA phenotype was more prevalent in North America (76%) than Europe (40%), and all isolates had elevated resistance rates to other antimicrobial classes including the following: 1) chloramphenicol resistance among E. faecalis being greater in North America than in Europe (28.6% versus 7.1%, respectively) but reversed among E. faecium (0.5% and 15.0%, the latter due to clonal occurrences); 2) ciprofloxacin resistance in North America >99% for both species and in Europe varying from 85.7% to 87.5%; 3) rare occurrences of linezolid resistance in North America (0.8% to 1.8%) due to G2576U ribosomal mutation; 4) higher quinupristin/dalfopristin resistance observed among European E. faecium strains (10.0% versus 0.6%); and 5) higher rifampin resistance rates among European E. faecalis (21.4% versus 5.4%). Thirty-five MDR epidemic clusters were identified by PFGE in 21 North American and 2 European medical centers including the following: 1) VanA (20 sites, 27 clonal occurrences) and VanB (1 site, 2 clonal occurrences); 2) elevated quinupristin/dalfopristin MIC results (not vatD/E, 3 sites); and 3) chloramphenicol resistance (chloramphenicol acetyltransferase-positive strains, 3 sites). The esp gene, part of the putative E. faecium pathogenicity island and a marker for the clonal complex-17 lineage, was detected in 76% of vancomycin-resistant E. faecium. Clonal spread appears to be a dominant factor of MDR VRE dissemination on both continents, and further monitoring is critical to assist in the control of these resistant pathogens.

The morbidity and cost for cure associated with skin and soft tissue infections (SSTIs) have recently become more complicated because of the increasing prevalence of multidrug-resistant pathogens associated with this healthcare problem. The SENTRY Antimicrobial Surveillance Program has been monitoring SSTI since 1997, and now presents data from 3 continents over a 7-year period (1998-2004). Isolates were tested by reference broth microdilution methods at a central laboratory using the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) methods and interpretative criteria. The predominant pathogens included Staphylococcus aureus (ranked 1st in all geographic regions), Pseudomonas aeruginosa, Escherichia coli, and Enterococcus spp. A considerable variation in the methicillin (oxacillin)-resistant S. aureus rate was noted between countries and continents, with the overall rate highest in North America (35.9%) compared with Latin America (29.4%) and Europe (22.8%). Vancomycin-resistant Enterococcus spp. increased in Europe (4.1%) and North America (6.2%) during the period, but remained low and relatively unchanged in Latin America. Among the P. aeruginosa isolates tested, susceptibility to imipenem was much lower in Latin America (65.3%) compared with the other regions (80.7-88.7%), and resistance being associated with an increase in metallo-beta-lactamase-producing strains in Latin America and in some European countries. Multidrug-resistant strains of P. aeruginosa were also more of a concern in Latin America (24.7%) compared with Europe (10.8%) or North America (3.2%). Latin America also had the highest occurrence of extended-spectrum beta-lactamase-producing isolates among E. coli (15.1%) and Klebsiella spp. (48.0%) when compared with other regions. Continued surveillance of pathogen prevalence and antimicrobial resistance patterns should provide information that is important to improve empiric care particularly in the hospital environment.

Background: Since chronic low back pain (CLBP) is a complex biopsychosocial problem the ideal treatment is multimodal and multidisciplinary. However, in many countries, primary-care physicians care for many people with CLBP and have a pivotal role in selecting patients for more intensive treatments when these are available. Guidelines on the general use of strong opioids in chronic non-cancer pain have been published but, until now, no specific guidelines were available on their use in chronic low back pain. Given the prevalence of CLBP, and the complex nature of this multifactorial condition, it was felt that specific, evidence-based recommendations, with a focus on primary-care treatment, would be helpful., Methods: An expert panel drawn from across Europe including pain specialists, anaesthetists, neurologists, rheumatologists, a general practitioner, an epidemiologist and the chairman of a pain charity was therefore convened. The aim of the group was to develop evidence-based recommendations that could be used as a framework for more specific guidelines to reflect local differences in the availability of specialist pain services and in the legal status and availability of strong opioids. Statements were based on published evidence (identified by a literature search) wherever possible, and supported by clinical experience when suitable evidence was lacking., Recommendations: Strong opioids have a role in the treatment of low back pain when other treatments have failed. They should be prescribed as part of a multimodal, and ideally interdisciplinary, treatment plan. The aim of treatment should be to relieve pain and facilitate rehabilitation.

The empiric treatment of patients with bloodstream infections (BSI) has become more complicated in an era of increasing antimicrobial resistance. The SENTRY Antimicrobial Surveillance Program has monitored BSI from patients in medical centers worldwide since 1997. During 1997-2002, a total of 81,213 BSI pathogens from North America, Latin America, and Europe were tested for antimicrobial susceptibility. S. aureus, E. coli, and coagulase-negative staphylococci were the three most common BSI pathogens in all three regions each year. Prevalence variability was noted in regions for some species, including higher rates of isolation of E. coli in Europe, Enterococcus spp. in North America, and Gram-negative enteric and nonenteric species in Latin America. Patient age analysis showed the most common BSI pathogen among neonates was coagulase-negative staphylococci and among elderly patients, E. coli. Resistance among BSI pathogens was much more prevalent in nosocomial infections and in patients in intensive care units (ICUs); age differences were also noted. Geographically, oxacillin-resistant S. aureus (39.1%, 2002) and vancomycin-resistant enterococci (17.7%, 2002) were highest in North America, and extended-spectrum beta-lactamase-producing Klebsiella spp. (35.8-46.7%) and multidrug-resistant P. aeruginosa (18.7%, 2002) were highest in Latin America. Activity of commonly used antimicrobial agents remained relatively stable in North America, except in the case of vancomycin-resistant enterococci (20% decline between 1997 and 2002). An epidemiologic investigation of oxacillin-resistant S. aureus in North America identified 10 significant clones (ribotypes) and the common resistance patterns associated with them. Surveillance of BSI pathogens is needed to determine trends of resistance and provide useful information regarding patient risk factors and geographic differences.

Objective: To compare the health-related quality of life (HRQoL) of overactive bladder (OAB) patients foilowing treatment with tolterodine extended-release (ER) 4 mg once daily versus placebo., Study Design: Multinational, placebo-controlled, randomized, double-blind 12-week study., Population: Patients with urinary frequency ( > or = 8 micturitions/24 hours over a 7-day period), urge incontinence ( > or = 5 episodes/week), and symptoms of OAB for at least 6 months were eligible for inclusion. Patients (81% female) received oral therapy with tolterodine ER (n = 507) or placebo (n = 508) for 12 weeks., Outcomes Measured: HRQoL was assessed using the King's Health Questionnaire (KHQ) and Medical Outcomes Study Short Form 36-item questionnaire (SF-36). Patients also rated their bladder condition. Assessments were performed at baseline and at the end of treatment., Results: At end of treatment, KHQ domains selected a priori as primary HRQoL end points (incontinence impact and role limitations) significantly improved (P < or = .001) with tolterodine ER. Domains selected a priori as secondary end points (physical limitations, sleep and energy, severity [coping] measures, and symptom severity) were also significantly improved (P < or = .006) following treatment with tolterodine ER. The tolterodine ER group had decreased symptom severity and statistically significant improvements in patient rating of bladder control compared with the placebo group at end of treatment. No treatment differences were detected using the SF-36., Conclusion: Many aspects of HRQoL, as measured by the KHQ, showed statistically significant improvement following treatment with tolterodine ER. These HRQoL improvements were consistent with clinical efficacy benefits. Patients receiving tolterodine ER experienced overall improvement in their condition that was associated with an important impact on their HRQoL.