Quantifying urban attractiveness from the distribution and density of digital footprints

In the past, sensors networks in cities have been limited to fixed sensors, embedded in particular locations, under centralised control. Today, new applications can leverage wireless devices and use them as sensors to create aggregated information. In this paper, we show that the emerging patterns unveiled through the analysis of large sets of aggregated digital footprints can provide novel insights into how people experience the city and into some of the drivers behind these emerging patterns. We particularly explore the capacity to quantify the evolution of the attractiveness of urban space with a case study of in the area of the New York City Waterfalls, a public art project of four man-made waterfalls rising from the New York Harbor. Methods to study the impact of an event of this nature are traditionally based on the collection of static information such as surveys and ticket-based people counts, which allow to generate estimates about visitors’ presence in specific areas over time. In contrast, our contribution makes use of the dynamic data that visitors generate, such as the density and distribution of aggregate phone calls and photos taken in different areas of interest and over time. Our analysis provides novel ways to quantify the impact of a public event on the distribution of visitors and on the evolution of the attractiveness of the points of interest in proximity. This information has potential uses for local authorities, researchers, as well as service providers such as mobile network operators.

Optimum pilot overhead in wireless communication: a unified treatment of continuous and block-fading channels

The optimization of the pilot overhead in wireless fading channels is investigated, and the dependence of this overhead on various system parameters of interest (e.g., fading rate, signal-to-noise ratio) is quantified. The achievable pilot-based spectral efficiency is expanded with respect to the fading rate about the no-fading point, which leads to an accurate order expansion for the pilot overhead. This expansion identifies that the pilot overhead, as well as the spectral efficiency penalty with respect to a reference system with genie-aided CSI (channel state information) at the receiver, depend on the square root of the normalized Doppler frequency. It is also shown that the widely-usedblock fading model is a special case of more accurate continuous fading models in terms of the achievable pilot-based spectral efficiency. Furthermore, it is established that the overhead optimization for multiantenna systems is effectively the same as for single-antenna systems with thenormalized Doppler frequency multiplied by the number of transmit antennas.

Social and medical vulnerability factors of emergency department frequent users in a universal health insurance system.

OBJECTIVES: The objectives were to identify the social and medical factors associated with emergency department (ED) frequent use and to determine if frequent users were more likely to have a combination of these factors in a universal health insurance system. METHODS: This was a retrospective chart review case-control study comparing randomized samples of frequent users and nonfrequent users at the Lausanne University Hospital, Switzerland. The authors defined frequent users as patients with four or more ED visits within the previous 12 months. Adult patients who visited the ED between April 2008 and March 2009 (study period) were included, and patients leaving the ED without medical discharge were excluded. For each patient, the first ED electronic record within the study period was considered for data extraction. Along with basic demographics, variables of interest included social (employment or housing status) and medical (ED primary diagnosis) characteristics. Significant social and medical factors were used to construct a logistic regression model, to determine factors associated with frequent ED use. In addition, comparison of the combination of social and medical factors was examined. RESULTS: A total of 359 of 1,591 frequent and 360 of 34,263 nonfrequent users were selected. Frequent users accounted for less than a 20th of all ED patients (4.4%), but for 12.1% of all visits (5,813 of 48,117), with a maximum of 73 ED visits. No difference in terms of age or sex occurred, but more frequent users had a nationality other than Swiss or European (n = 117 [32.6%] vs. n = 83 [23.1%], p = 0.003). Adjusted multivariate analysis showed that social and specific medical vulnerability factors most increased the risk of frequent ED use: being under guardianship (adjusted odds ratio [OR] = 15.8; 95% confidence interval [CI] = 1.7 to 147.3), living closer to the ED (adjusted OR = 4.6; 95% CI = 2.8 to 7.6), being uninsured (adjusted OR = 2.5; 95% CI = 1.1 to 5.8), being unemployed or dependent on government welfare (adjusted OR = 2.1; 95% CI = 1.3 to 3.4), the number of psychiatric hospitalizations (adjusted OR = 4.6; 95% CI = 1.5 to 14.1), and the use of five or more clinical departments over 12 months (adjusted OR = 4.5; 95% CI = 2.5 to 8.1). Having two of four social factors increased the odds of frequent ED use (adjusted = OR 5.4; 95% CI = 2.9 to 9.9), and similar results were found for medical factors (adjusted OR = 7.9; 95% CI = 4.6 to 13.4). A combination of social and medical factors was markedly associated with ED frequent use, as frequent users were 10 times more likely to have three of them (on a total of eight factors; 95% CI = 5.1 to 19.6). CONCLUSIONS: Frequent users accounted for a moderate proportion of visits at the Lausanne ED. Social and medical vulnerability factors were associated with frequent ED use. In addition, frequent users were more likely to have both social and medical vulnerabilities than were other patients. Case management strategies might address the vulnerability factors of frequent users to prevent inequities in health care and related costs.

Delay of extubation in neonates and children after cardiac surgery: impact of ventilator-associated pneumonia.

OBJECTIVE: This study was undertaken to determine the delay of extubation attributable to ventilator-associated pneumonia (VAP) in comparison to other complications and complexity of surgery after repair of congenital heart lesions in neonates and children. METHODS: Cohort study in a pediatric intensive care unit of a tertiary referral center. All patients who had cardiac operations during a 22-month period and who survived surgery were eligible (n = 272, median age 1.3 years). Primary outcome was time to successful extubation. Primary variable of interest was VAP Surgical procedures were classified according to complexity. Cox proportional hazards models were calculated to adjust for confounding. Potential confounders comprised other known risk factors for delayed extubation. RESULTS: Median time to extubation was 3 days. VAP occurred in 26 patients (9.6%). The rate of VAP was not associated with complexity of surgery (P = 0.22), or cardiopulmonary bypass (P = 0.23). The adjusted analysis revealed as further factors associated with delayed extubation: other respiratory complications (n = 28, chylothorax, airway stenosis, diaphragm paresis), prolonged inotropic support (n = 48, 17.6%), and the need for secondary surgery (n = 51, 18.8%; e.g., re-operation, secondary closure of thorax). Older age promoted early extubation. The median delay of extubation attributable to VAP was 3.7 days (hazards ratio HR = 0.29, 95% CI 0.18-0.49), exceeding the effect size of secondary surgery (HR = 0.48) and other respiratory complications (HR = 0.50). CONCLUSION: VAP accounts for a major delay of extubation in pediatric cardiac surgery.

Five-Year Denosumab Treatment of Postmenopausal Women with Osteoporosis: Results from the first two Years of the Freedom Trial Extension

Objectives : The FREEDOM trial1 open-label extension is designed to evaluate the long-term efficacy and safety of denosumab for up to 10 years. We report the results from the first 2 years of the extension, representing up to 5 years of denosumab exposure.Materials/Methods : Postmenopausal women enrolled in the extension previously completed FREEDOM. During the extension, all women receive denosumab (60 mg) every 6 months and calcium and vitamin D daily. For the FREEDOM denosumab group, the data reflect 5 years of denosumab treatment (long-term group). For the FREEDOM placebo group, the data reflect 2 years of denosumab treatment (de novo group). P-values are descriptive.Results : There were 4550 (70.2%) FREEDOM women enrolled in the extension (2343 long-term; 2207 de novo). During the 4th and 5th years of denosumab treatment, the long-term group had further 1.9% and 1.7% increases in lumbar spine BMD and further 0.7% and 0.6% increases in total hip BMD (all P<0.0001 compared with extension baseline). Total BMD increases with 5-year denosumab treatment were 13.7% (lumbar spine) and 7.0% (total hip). In the de novo group, BMD increased during the first 2 years of denosumab treatment by 7.9% (lumbar spine) and 4.1% (total hip) (all P<0.0001 compared with extension baseline). After denosumab administration, serum CTX was rapidly and maximally reduced in both groups with the characteristic attenuation observed at the end of the dosing interval, as previously reported.2 Incidences of new vertebral and nonvertebral fractures were low and below rates observed in the FREEDOM placebo group. Adverse event reports were similar for both groups: in the long-term group, 83.4% reported AEs and 18.9% were serious. In the de novo group, the percentages were 82.8% and 19.4%, respectively. In FREEDOM, the respective percentages were 92.8% and 25.8% in the denosumab group and 93.1% and 25.1% in the placebo group. Two subjects in the de novo group had AEs adjudicated to ONJ which healed without further complications ; one resolved within the 6-month dosing interval and denosumab was continued. There were no atypical femoral fractures.Conclusions : Denosumab treatment for 5 years was well-tolerated and continued to significantly reduce CTX and significantly increase BMD. Reference: 1)Cummings;NEJM;2009;361:756, 2)Eastell;JBMR;2010; doi-10.1002/jbmr.251 Disclosure of Interest: This study was funded by Amgen; S Papapoulos: Consulting fees from Amgen, Merck, Novartis, Procter & Gamble, GSK, and Wyeth; R Chapurlat: Research grants and/or consulting fees from Amgen, Merck, Novartis, sanofi-aventis, Roche, Servier, and Warner Chilcott;ML Brandi: Research grants and/or consulting fees from Amgen, Eli Lily, GSK, MSD, NPS, Nycomed, Roche, Servier, and Stroder; JP Brown: Research grants and/or consulting or speaking fees from Abott, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, Roche, Novartis, Merck, and Warner Chilcott; E Czerwinski: Research grants from Amgen, Astrazeneca, Danone Research, Eli Lilly, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SantoSolve AS, and Servier; N Daizadeh, A Grauer, C Libanati: Employed by Amgen and own Amgen stocks or stock options; M-A Krieg, D Mellstrom, H Resch: None; S Radominski: Research grants from Amgen, Pfizer, Novartis, Bristol-Myers Squibb, Roche, and Aventis; Z Man: Lecture fees and/or consulting fees from Merck, Novartis, Roche, and sanofi-aventis. Novartis steering committee member; JA Roman: Research grants from Roche; J-Y Reginster: Research grants, consulting fees, and/or lecture fees from Amgen, Analis, Bristol Myers Squibb, Ebewee Pharma, Genevrier, GSK, IBSA, Lilly, Merck Sharp & Dhome, Negma, Novartis, Novo-Nordisk, Nycomed, NPS, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, UCB, Wyeth, and Zodiac; C Roux: Research grants and/or consulting fees from Amgen, MSD, Novartis, Servier, and Roche; SR Cummings: Research grants and/or consulting fees from Amgen, Eli Lilly, Novartis, and Merck; HG Bone: Research grants and/or consulting or speaking fees from Amgen, Eli Lilly, Merck, Nordic Bioscience, Novartis, Takeda, and Zelos

Androgen dependence of hirsutism, acne, and alopecia in women: retrospective analysis of 228 patients investigated for hyperandrogenism.

Hirsutism, acne, alopecia, and oligo-amenorrhea are clinical expressions of hyperandrogenism, one of the most frequent endocrine disorders in women of reproductive age. Women referred to our endocrine clinics for skin symptoms of hyperandrogenism underwent a laboratory workup to evaluate hormone measurements and received antiandrogen therapy. We retrospectively analyzed the outcome of 228 consecutive patients investigated over 6 years.Patients with hirsutism had higher levels of androstenedione, dehydroepiandrosterone sulfate (DHEAS), and salivary testosterone; lower levels of sex hormone-binding globulin (SHBG); and a higher prevalence of oligo-amenorrhea than patients with alopecia, while patients with acne showed intermediate values. Hirsutism score correlated positively with androstenedione, DHEAS, and salivary testosterone, and correlated negatively with SHBG; salivary testosterone showed the highest correlation coefficient. Total testosterone was not significantly different among patients with hirsutism, alopecia, or acne, and did not significantly correlate with hirsutism score. Hirsutism and oligo-amenorrhea were the most sensitive symptoms of hyperandrogenism, and no androgenic parameter alone allowed us to identify all cases of hyperandrogenism.Patients of central European origin sought consultation with milder hirsutism scores than patients of southern European origin. There was, however, no difference in the clinical-biological correlation between these groups, arguing against differences in skin sensitivity to androgens.Polycystic ovary syndrome, defined as hyperandrogenism (hirsutism or elevated androgens) and oligo-amenorrhea, was diagnosed in 63 patients (27.6%), an underestimate compared with other reports that include systematic ovarian ultrasound studies. Neither pelvic ultrasound, used in a limited number of cases, nor the luteinizing hormone/follicle-stimulating hormone ratio helped to distinguish patients with polycystic ovary syndrome from the other diagnostic groups. These included hyperandrogenism (hirsutism or elevated androgens) and eumenorrhea (101 patients; 44.3%); normal androgens (acne or alopecia and eumenorrhea) (51 patients; 22.4%); isolated low SHBG (7 patients; 3.1%); nonclassical congenital adrenal hyperplasia (4 patients; 1.8% of total, 4.9% of patients undergoing cosyntropin stimulation tests); and ovarian tumor (2 patients; 0.9%).Ethinylestradiol and high-dose cyproterone acetate treatment lowered the hirsutism score to 53.5% of baseline at 1 year, and was also effective in treating acne and alopecia. The clinical benefit is ascribed to the peripheral antiandrogenic effect of cyproterone acetate as well as the hormone-suppressive effect of this combination. Salivary testosterone showed the most marked proportional decrease of all the androgens under treatment. Cost-effectiveness and tolerance of ethinylestradiol and high-dose cyproterone acetate compared well with other antiandrogenic drug therapies for hirsutism. The less potent therapy with spironolactone only, a peripheral antiandrogen without hormone-suppressive effect, was effective in treating isolated alopecia in patients with normal androgens.

Study of protein complexes

Summary : A lot of information can be obtained on proteins when proteomics methods are used. In our study, we aimed to characterize complexes containing pro-apoptotic proteins by different proteomics methods and finally focused on PIDD (p53-induced protein with a death domain), for which the most interesting results were obtained. PIDD has been shown to function as a molecular switch between genotoxic stress-induced apoptotis and genotoxic stress-induced cell survival through NF-κB activation. To exert these two functions, PIDD forms alternate complexes respectively with caspase2 and CRADD on one hand and RIP 1 and NEMO on the other hand. The first part of our study focuses on the processing of PIDD. PIDD full length (FL) is constitutively cleaved into three fragments, an N-terminal one (PIDD-N) and two fragments containing the C-terminus (PIDD-C and PIDD-CC). Localization of the two PIDD cleavage sites by mass spectrometry (MS) allowed to understand that PIDD is probably not cleaved by proteases but is subject to protein (self-)splicing and also to map the PIDD-N, PIDD-C and PIDD-CC fragments exactly. Further characterization of these three fragments by Tinel et al. (Tinel et al., 2007) showed that PIDD-C is involved in activation of an apoptotic pathway while PIDD-CC is involved in NF-κB activation. We also found that PIDD is subject to proline-directed phosphorylation at two serine residues in PIDD-N, the regulatory fragment of PIDD. The second part of the study aimed at identifying by proteomics techniques proteins that co-purify with PIDD and therefore are putative cellular interaction partners. In this respect we analyzed samples obtained in different conditions or with different PIDD constructs corresponding to processed fragments. This allowed us to identify a large number of potential interactors for PIDD. For example, by comparing data obtained from PIDD-C and PIDD-FL affinity purifications, we found that the Hsp90 chaperone system interacts strongly with PIDD-N. In the third part of this study, we developed methods to selectively and rapidly quantify by MS proteins of interest in PIDD affinity purifications or negative controls. Using these tools we detected significant changes in PIDD-FL-copurifying proteins treated by heat shock. Overall, our studies provide informative data on the processing of PIDD and its possible involvement in several molecular pathways.

Are patterns of bone loss in anorexic and postmenopausal women similar? Preliminary results using high resolution peripheral computed tomography.

This study intended to compare bone density and architecture in three groups of women: young women with anorexia nervosa (AN), an age-matched control group of young women, and healthy late postmenopausal women. Three-dimensional peripheral quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal radius, a technology providing measures of cortical and trabecular bone density and microarchitecture, was performed in the three cohorts. Thirty-six women with AN aged 18-30years (mean duration of AN: 5.8years), 83 healthy late postmenopausal women aged 70-81 as well as 30 age-matched healthy young women were assessed. The overall cortical and trabecular bone density (D100), the absolute thickness of the cortical bone (CTh), and the absolute number of trabecules per area (TbN) were significantly lower in AN patients compared with healthy young women. The absolute number of trabecules per area (TbN) in AN and postmenopausal women was similar, but significantly lower than in healthy young women. The comparison between AN patients and post-menopausal women is of interest because the latter reach bone peak mass around the middle of the fertile age span whereas the former usually lose bone before reaching optimal bone density and structure. This study shows that bone mineral density and bone compacta thickness in AN are lower than those in controls but still higher than those in postmenopause. Bone compacta density in AN is similar as in controls. However, bone inner structure in AN is degraded to a similar extent as in postmenopause. This last finding is particularly troubling.

The impact of information on decision-making in palliative care

Résumé Ce travail vise à clarifier les résultats contradictoires de la littérature concernant les besoins des patients d'être informés et de participer à la prise de décision. La littérature insiste sur le contenu de l'information comme base de la prise de décision, bien qu'il existe des preuves que d'autres contenus sont importants pour les patients. La thèse essaie en outre d'identifier des possibilités de mieux répondre aux préférences d'information et de participation des patients. Les travaux ont porté en particulier sur les soins palliatifs. Une analyse de la littérature donne un aperçu sur les soins palliatifs, sur l'information des patients et sur leur participation à la prise de décisions thérapeutiques. Cette analyse résume les résultats d'études précédentes et propose un: modèle théorique d'information, de prise de décision et de relation entre ces deux domaines. Dans le cadre de ce travail, deux études empiriques ont utilisé des questionnaires écrits adressés à des personnes privées et à des professionnels de la santé, couvrant la Suisse et le Royaume Uni, pour identifier d'éventuelles différences entre ces deux pays. Les enquêtes ont été focalisées sur des patients souffrant de cancer du poumon. Les instruments utilisés pour ces études proviennent de la littérature afin de les rendre comparables. Le taux de réponse aux questionnaires était de 30-40%. La majorité des participants aux enquêtes estime que les patients devraient: - collaborer à la prise de décision quant à leur traitement - recevoir autant d'information que possible, positive aussi bien que négative - recevoir toutes les informations mentionnées dans le questionnaire (concernant la maladie, le diagnostic et les traitements), tenant compte de la diversité des priorités des patients - être soutenus par des professionnels de la santé, leur famille, leurs amis et/ou les personnes souffrant de la même maladie En plus, les participants aux enquêtes ont identifié divers contenus de l'information aux patients souffrant d'une maladie grave. Ces contenus comprennent entre autres: - L'aide à la prise de décision concernant le traitement - la possibilité de maintenir le contrôle de la situation - la construction d'une relation entre le patient et le soignant - l'encouragement à faire des projets d'avenir - l'influence de l'état émotionnel - l'aide à la compréhension de la maladie et de son impact - les sources potentielles d'états confusionnels et d'états anxieux La plupart des contenus proposés sont positifs. Les résultats suggèrent la coexistence possible de différents contenus à un moment donné ainsi que leur changement au cours du temps. Un modèle est ensuite développé et commenté pour présenter le diagnostic d'une maladie grave. Ce modèle est basé sur la littérature et intègre les résultats des études empiriques réalisées dans le cadre de ce travail. Ce travail analyse également les sources préférées d'information et de soutien, facteurs qui peuvent influencer ou faire obstacle aux préférences d'information et de participation. Les deux groupes de participants considèrent les médecins spécialistes comme la meilleure source d'information. En ce qui concerne le soutien, les points de vue divergent entre les personnes privées et les professionnels de la santé: généralement, les rôles de soutien semblent peu définis parmi les professionnels. Les barrières à l'information adéquate du patient apparaissent fréquemment liées aux caractéristiques des professionnels et aux problèmes d'organisation. Des progrès dans ce domaine contribueraient à améliorer les soins fournis aux patients. Finalement, les limites des études empiriques sont discutées. Celles-ci comprennent, entre autres, la représentativité restreinte des participants et les objections de certains groupes de participants à quelques détails des questionnaires. Summary The present thesis follows a call from the current body of literature to better understand patient needs for information and for participation in decision-making, as previous research findings had been contradictory. Information so far seems to have been considered essentially as a means to making treatment decisions, despite certain evidence that it may have a number of other values to patients. Furthermore, the thesis aims to identify ways to optimise meeting patient preferences for information and participation in treatment decisions. The current field of interest is palliative care. An extensive literature review depicts the background of current concepts of palliative care, patient information and patient involvement into treatment decisions. It also draws together results from previous studies and develops a theoretical model of information, decision-making, and the relationship between them. This is followed by two empirical studies collecting data from members of the general public and health care professionals by means of postal questionnaires. The professional study covers both Switzerland and the United Kingdom in order to identify possible differences between countries. Both studies focus on newly diagnosed lung cancer patients. The instruments used were taken from the literature to make them comparable. The response rate in both surveys was 30-40%, as expected -sufficient to allow stastical tests to be performed. A third study, addressed to lung cancer patients themselves, turned out to require too much time within the frame available. A majority of both study populations thought that patients should: - have a collaborative role in treatment-related decision-making -receive as much information as possible, good or bad - receive all types of information mentioned in the questionnaire (about illness, tests, and treatment), although priorities varied across the study populations - be supported by health professionals, family members, friends and/or others with the same illness Furthermore they identified various 'meanings' information may have to patients with a serious illness. These included: - being an aid in treatment-related decision-making - allowing control to be maintained over the situation - helping the patient-professional relationship to be constructed - allowing plans to be made - being positive for the patient's emotional state - helping the illness and its impact to be understood - being a source of anxiety - being a potential source of confusion to the patient Meanings were mostly positive. It was suggested that different meanings could co-exist at a given time and that they might change over time. A model of coping with the disclosure of a serious diagnosis is then developped. This model is based on existing models of coping with threatening events, as takeñ from the literature [ref. 77, 78], and integrates findings from the empirical studies. The thesis then analyses the remaining aspects apparent from the two surveys. These range from the identification of preferred information and support providers to factors influencing or impeding information and participation preferences. Specialist doctors were identified by both study populations as the best information providers whilst with regard to support provision views differed between the general public and health professionals. A need for better definition of supportive roles among health care workers seemed apparent. Barriers to information provision often seem related to health professional characteristics or organisational difficulties, and improvements in the latter field could well help optimising patient care. Finally, limitations of the studies are discussed, including questions of representativness of certain results and difficulties with or objections against questionnaire details by some groups of respondents.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study.

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400 copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

Comfort of the patient's family in an Intensive Care Unit related to welcoming

This study aimed to identify the level of comfort of families of patients in a critical health condition related to the welcoming practices performed by the hospital staff. Interviews were conducted with 250 relatives in hospitals of the state Bahia, using a Likert scale. Data were analyzed as percentages and quartiles. For nine of the 12 statements of the scale, most relatives scored their comfort level between very and totally comfortable, median of 4,revealing kindness, tranquility and friendly communication with family members. More than half of the sample scored its level as not at all to more or less comfortable, median of 3, for statements about demonstration of interest towards the relative by the staff and flexible visiting of the patient. The necessity of greater interest of the team in the condition and needs of the family was observed. Promoting comfort from the dimension of welcoming demands interdisciplinary actions grounded in humanistic philosophy, in which the nurse has an important role to play.

Effects of phylogenetic signal on ancestral state reconstruction.

One of the standard tools used to understand the processes shaping trait evolution along the branches of a phylogenetic tree is the reconstruction of ancestral states (Pagel 1999). The purpose is to estimate the values of the trait of interest for every internal node of a phylogenetic tree based on the trait values of the extant species, a topology and, depending on the method used, branch lengths and a model of trait evolution (Ronquist 2004). This approach has been used in a variety of contexts such as biogeography (e.g., Nepokroeff et al. 2003, Blackburn 2008), ecological niche evolution (e.g., Smith and Beaulieu 2009, Evans et al. 2009) and metabolic pathway evolution (e.g., Gabaldón 2003, Christin et al. 2008). Investigations of the factors affecting the accuracy with which ancestral character states can be reconstructed have focused in particular on the choice of statistical framework (Ekman et al. 2008) and the selection of the best model of evolution (Cunningham et al. 1998, Mooers et al. 1999). However, other potential biases affecting these methods, such as the effect of tree shape (Mooers 2004), taxon sampling (Salisbury and Kim 2001) as well as reconstructing traits involved in species diversification (Goldberg and Igić 2008), have also received specific attention. Most of these studies conclude that ancestral character states reconstruction is still not perfect, and that further developments are necessary to improve its accuracy (e.g., Christin et al. 2010). Here, we examine how different estimations of branch lengths affect the accuracy of ancestral character state reconstruction. In particular, we tested the effect of using time-calibrated versus molecular branch lengths and provide guidelines to select the most appropriate branch lengths to reconstruct the ancestral state of a trait.

Rapid Improvement in Health-Related Quality of Life in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by interleukin (IL)-1b. Canakinumab inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 wk double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150mg divided in doses every 4 wks (50þ50þ25þ25mg [q4wk]) or colchicine 0.5mg p.o. daily for 16 wks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to number of flares occurring during first 16 wks. Secondary outcomes included number of patients with flares and C-reactive protein (CRP) levels during the first 16 wks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine couldn't be determined. Based on a negative binomialmodel, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25mg 0.60, 50mg 0.34, 100mg 0.28, 200mg 0.37, 300mg 0.29, q4wk 0.38; p_0.05). Percentage of patients with flares was lower for all canakinumab groups (25mg 27.3%, 50mg 16.7%, 100mg 14.8%, 200mg 18.5%, 300mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p_0.05 for all). Median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN¼3 mg/L) throughout the 16 wk period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg), 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. 1 fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusions: In this randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine and was well tolerated.Disclosure statement: U.A., A.B., G.K., D.R. and P.S. are employees of and have stock options or bold holdings with Novartis Pharma AG. E.M. is a principal investigator for Novartis Pharmaceuticals Corporation. E.N. has received consulting fees from Roche. N.S. has received research grants from Novartis Pharmaceuticals Corporation. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Soil Survey of Black Hawk County, Iowa, 2005

The general soil map, which is a color map, shows the survey area divided into groups of associated soils called general soil map units. This map is useful in planning the use and management of large areas. To find information about your area of interest, locate that area on the map, identify the name of the map unit in the area on the color-coded map legend, then refer to the section General Soil Map Units for a general description of the soils in your area.

Soil Survey of Clay County, Iowa, 2005

The general soil map, which is a color map, shows the survey area divided into groups of associated soils called general soil map units. This map is useful in planning the use and management of large areas. To find information about your area of interest, locate that area on the map, identify the name of the map unit in the area on the color-coded map legend, then refer to the section General Soil Map Units for a general description of the soils in your area.