Gaussian Process models for ubiquitous user comfort preference sampling; global priors, active sampling and outlier rejection.

This paper presents a ubiquitous thermal comfort preference learning study in a noisy environment. We introduce Gaussian Process models into this field and show they are ideal, allowing rejection of outliers, deadband samples, and produce excellent estimates of a users preference function. In addition, informative combinations of users preferences becomes possible, some of which demonstrate well defined maxima ideal for control signals. Interestingly, while those users studied have differing preferences, their hyperparameters are concentrated allowing priors for new users. In addition, we present an active learning algorithm which estimates when to poll users to maximise the information returned

The molecular epidemiology of human immunodeficiency virus type 1 in six cities in Britain and Ireland

The authors sequenced the p17 coding regions of the gag gene from 211 patients infected either through injecting drug use (IDU) or by sexual intercourse between men from six cities in Scotland, N. England, N. Ireland, and the Republic of Ireland. All sequences were of subtype 5. Phylogenetic analysis revealed substantial heterogeneity in the sequences from homosexual men. In contrast, sequence from over 80% of IDUs formed a relatively tight cluster, distinct both from those of published isolates and of the gay men. There was no large-scale clustering of sequences by city in either risk group, although a number of close associations between pairs of individuals were observed. From the known date of the HIV-1 epidemic among IDUs in Edinburgh, the rate of sequence divergence at synonymous sites is estimated to be about 0.8%. On this basis it has been estimated that the date of divergence of the sequences among homosexual men to be about 1975, which may correspond to the origin of the B subtype epidemic

Patient and physician factors associated with participation in cervical and uterine cancer trials: An NRG/GOG247 study

AbstractPurposeThe aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials.MethodsProspective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial. Odds ratios (OR) and 95% confidence intervals (CI) for significant (p<0.05) results reported.ResultsSixty institutions, 781 patients, and 150 physicians participated, 300/780 (38%) had a trial available, 290/300 had known participation status. Of these, 150 women enrolled (59.5%), 102 eligible did not enroll (35%), 38 (13%) were ineligible. Ethnicity and specialty of physician, practice type, data management availability, and patient age were significantly associated with trial availability. Patients with >4 comorbidities (OR 4.5; CI 1.7–11.8) had higher odds of trial ineligibility. Non-White patients (OR 7.9; CI 1.3–46.2) and patients of Black physicians had greater odds of enrolling (OR 56.5; CI 1.1–999.9) in a therapeutic trial. Significant patient therapeutic trial enrollment factors: belief trial may help (OR 76.9; CI 4.9–>1000), concern about care if not on trial (OR12.1; CI 2.1–71.4), pressure to enroll (OR .27; CI 0.12–.64), caregiving without pay (OR 0.13; CI .02–.84). Significant physician beliefs were: patients would not do well on standard therapy (OR 3.6; CI 1.6–8.4), and trial would not be time consuming (OR 3.3; CI 1.3–8.1).ConclusionsTrial availability, patient and physician beliefs were factors identified that if modified could improve enrollment in cancer cooperative group clinical trials

Selected Contemporary Challenges of Ageing Policy

Among the scholars trying to grasp the nuances and trends of social policy, there are diverse perspectives, resulting not only from the extensive knowledge of the authors on the systematic approach to the issue of supporting older people but also from the grounds of the represented social gerontology schools. In the texts of Volume VII interesting are both distinct and coherent elements presenting the role of local, regional and global policies in the prism of the countries from which the authors originate: the Czech Republic, Slovenia, Lithuania, Latvia, Poland, Slovakia, Italy, Turkey, and the United States. The chapters show a wealth of methodological approaches to the perception of social policy and its tools. In the texts there are issues related to the idea of active ageing, discrimination against older people in the workplace, comparability of solutions friendly to employment of older adults in the Czech Republic, Poland, and Slovakia as well as focused on the importance of educational forms (universities of the third age, senior clubs, folk high schools, and other non-formal solutions) determining an active life in old age. This monograph also attempted to answer the question regarding how to transfer the idea of intergenerational learning into the realm of practice. This issue complements the chapter on the implementation of intergenerational programs in institutions providing long-term care support. The book also outlines a public policy on ageing in the perspective of the changes over the last few decades (Slovenia) and the case demonstrating solutions to accelerate self-reliance as a key to active ageing (Turkey)

The Non-linear Dynamics of Meaning-Processing in Social Systems

Social order cannot be considered as a stable phenomenon because it contains an order of reproduced expectations. When the expectations operate upon one another, they generate a non-linear dynamics that processes meaning. Specific meaning can be stabilized, for example, in social institutions, but all meaning arises from a horizon of possible meanings. Using Luhmann's (1984) social systems theory and Rosen's (1985) theory of anticipatory systems, I submit equations for modeling the processing of meaning in inter-human communication. First, a self-referential system can use a model of itself for the anticipation. Under the condition of functional differentiation, the social system can be expected to entertain a set of models; each model can also contain a model of the other models. Two anticipatory mechanisms are then possible: one transversal between the models, and a longitudinal one providing the modeled systems with meaning from the perspective of hindsight. A system containing two anticipatory mechanisms can become hyper-incursive. Without making decisions, however, a hyper-incursive system would be overloaded with uncertainty. Under this pressure, informed decisions tend to replace the "natural preferences" of agents and an order of cultural expectations can increasingly be shaped

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Identification and validation of ERK5 as a DNA damage modulating drug target in glioblastoma

Brain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)—the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease

Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma

YesBrain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)-the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease

Nontuberculous mycobacteria: I: Multicenter prevalence study in cystic fibrosis

Nontuberculous mycobacteria (NTM) are potential respiratory pathogens in cystic fibrosis (CF). To assess the species-specific prevalence and risk factors for acquisition, we conducted a prospective, cross-sectional study of the prevalence of NTM and clinical features of patients at 21 U.S. centers. Almost 10% of patients with CF who were 10 years or older were included (n = 986). The overall prevalence of NTM in sputum was 13.0% (range by center, 7-24%). Mycobacterium avium complex (72%) and Mycobacterium abscessus (16%) were the most common species. When compared with patients with CF without NTM, culture-positive subjects were older (26 vs. 22 years, p &lt; 0.001), had a higher FEV1 (60 vs. 54%, p 0.01), higher frequency of Staphylococcus aureus (43 vs. 31%, p 0.01), and lower frequency of Pseudomonas aeruginosa (71 vs. 82%, p &lt; 0.01). Molecular typing revealed that almost all patients within each center had unique NTM strains. In summary, NTM are common in patients with CF, but neither person-to-person nor nosocomial acquisition explained the high prevalence. Older age was the most significant predictor for isolation of NTM. The clinical significance of NTM in CF is incompletely defined, but patients with these organisms should be monitored with repeat cultures