Joining Forces of Bayesian and Frequentist Methodology: A Study for Inference in the Presence of Non-Identifiability

Increasingly complex applications involve large datasets in combination with non-linear and high dimensional mathematical models. In this context, statistical inference is a challenging issue that calls for pragmatic approaches that take advantage of both Bayesian and frequentist methods. The elegance of Bayesian methodology is founded in the propagation of information content provided by experimental data and prior assumptions to the posterior probability distribution of model predictions. However, for complex applications experimental data and prior assumptions potentially constrain the posterior probability distribution insufficiently. In these situations Bayesian Markov chain Monte Carlo sampling can be infeasible. From a frequentist point of view insufficient experimental data and prior assumptions can be interpreted as non-identifiability. The profile likelihood approach offers to detect and to resolve non-identifiability by experimental design iteratively. Therefore, it allows one to better constrain the posterior probability distribution until Markov chain Monte Carlo sampling can be used securely. Using an application from cell biology we compare both methods and show that a successive application of both methods facilitates a realistic assessment of uncertainty in model predictions.Comment: Article to appear in Phil. Trans. Roy. Soc.

The role of glacier mice in the invertebrate colonisation of glacial surfaces: the moss balls of the Falljökull, Iceland

Glacier surfaces have a surprisingly complex ecology. Cryoconite holes contain diverse invertebrate communities while other invertebrates, such as Collembola often graze on algae and windblown dead organic on the glacier surface. Glacier mice (ovoid unattached moss balls) occur on some glaciers worldwide. Studies of these glacier mice have concentrated on their occurrence and mode of formation. There are no reports of the invertebrate communities. But, such glacier mice may provide a suitable favourable habitat and refuge for a variety of invertebrate groups to colonise the glacier surface. Here we describe the invertebrate fauna of the glacier mice (moss balls) of the Falljökull, Iceland. The glacier mice were composed of Racomitrium sp. and varied in size from 8.0 to 10.0 cm in length. All glacier mice studied contained invertebrates. Two species of Collembola were present. Pseudisotoma sensibilis (Tullberg, 1876) was numerically dominant with between 12 and 73 individuals per glacier mouse while Desoria olivacea (Tullberg, 1871) occurred but in far lower numbers. Tardigrada and Nematoda had mean densities of approximately 200 and 1,000 respectively. No Acari, Arachnida or Enchytraeidae were observed which may be related to the difficulty these groups have in colonizing the glacier mice. We suggest that glacier mice provide an unusual environmentally ameliorated microhabitat for an invertebrate community dwelling on a glacial surface. The glacier mice thereby enable an invertebrate fauna to colonise an otherwise largely inhospitable location with implications for carbon flow in the system

Developing capacity in health informatics in a resource poor setting: lessons from Peru

The public sectors of developing countries require strengthened capacity in health informatics. In Peru, where formal university graduate degrees in biomedical and health informatics were lacking until recently, the AMAUTA Global Informatics Research and Training Program has provided research and training for health professionals in the region since 1999. The Fogarty International Center supports the program as a collaborative partnership between Universidad Peruana Cayetano Heredia in Peru and the University of Washington in the United States of America. The program aims to train core professionals in health informatics and to strengthen the health information resource capabilities and accessibility in Peru. The program has achieved considerable success in the development and institutionalization of informatics research and training programs in Peru. Projects supported by this program are leading to the development of sustainable training opportunities for informatics and eight of ten Peruvian fellows trained at the University of Washington are now developing informatics programs and an information infrastructure in Peru. In 2007, Universidad Peruana Cayetano Heredia started offering the first graduate diploma program in biomedical informatics in Peru

Sporadic renal cell carcinoma in young and elderly patients: are there different clinicopathological features and disease specific survival rates?

BACKGROUND: Sporadic renal cell carcinoma (RCC) is rare in young adults. In the present retrospective study we reviewed clinicopathological features and disease specific survival rates in young patients (≤45 years) with RCC and compared them to old patients (≥75 years) with RCC. METHODS: Between 1992 and 2005 a total of 1042 patients were treated for RCC at our institution. We found 70 patients 45 years or younger (YP) and 150 patients 75 years or older (OP) at time of diagnosis. There were no differences in therapeutical approaches between both groups. Clinical and biologic parameters at diagnosis were compared and subjected to uni- and multivariate analysis to study cancer specific survival and progression rate. Mean postoperative follow-up in both groups was 50.1 months. RESULTS: Mean age was 39 years in YP and 80 years in OP, respectively. YP demonstrated significantly lower stage (pT1-pT2 N0 M0, p = 0.03), lower tumor grade (p = 0.01) and higher male-to-female ratio (p < 0.001). The rate of lymph node metastases or distant metastatic disease at presentation did not differ significantly between both groups. In multivariate analysis young age was independently associated with a higher 5-year cancer specific survival (95.2% vs. 72.3%, p = 0.009) and a lower 5-year progression rate (11.3% vs. 42.5%, p = 0.002). CONCLUSION: Sporadic RCC in young patients have lower tumor stages and grades and a better outcome compared to elderly. Age≤45 years was an independent prognostic factor for survival and progression

The Harris hip score: Do ceiling effects limit its usefulness in orthopedics?: A systematic review

The Harris hip score (HHS), a disease-specific health status scale that is frequently used to measure the outcome of total hip arthroplasty, has never been validated properly. A questionnaire is suitable only when all 5 psychometric properties are of sufficient quality. We questioned the usefulness of the HHS by investigating its content validity. We performed a systematic review based on a literature search in PubMed, Embase, and the Cochrane Library for descriptive studies published in 2007. 54 studies (59 patient groups) met our criteria and were included in the data analysis. To determine the content validity, we calculated the ceiling effect (percentage) for each separate study and we pooled data to measure the weighted mean. A subanalysis of indications for THA was performed to differentiate the populations for which the HHS would be suitable and for which it would not. A ceiling effect of 15% or less was considered to be acceptable. Over half the studies (31/59) revealed unacceptable ceiling effects. Pooled data across the studies included (n = 6,667 patients) suggested ceiling effects of 20% (95%CI: 18-22). Ceiling effects were greater (32%, 95%CI:12-52) in those patients undergoing hip resurfacing arthroplasty. Although the Harris hip score is widely used in arthroplasty research on outcomes, ceiling effects are common and these severely limit its validity in this field of researc

Extragalactic Results from the Infrared Space Observatory

More than a decade ago the IRAS satellite opened the realm of external galaxies for studies in the 10 to 100 micron band and discovered emission from tens of thousands of normal and active galaxies. With the 1995-1998 mission of the Infrared Space Observatory the next major steps in extragalactic infrared astronomy became possible: detailed imaging, spectroscopy and spectro-photometry of many galaxies detected by IRAS, as well as deep surveys in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about the nature of the energy source(s) and about the physical conditions in galaxies. ISO's surveys for the first time explore the infrared emission of distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in press), a gzip'd pdf file (667kB) is also available at http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g

Trans-Epithelial Immune Cell Transfer during Suckling Modulates Delayed-Type Hypersensitivity in Recipients as a Function of Gender

INTRODUCTION: Breast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult. METHODS: Non-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP) transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls. RESULTS: Despite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3-4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3-4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH) response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam) amplified a subsequent DTH response in females and yet suppressed one in males. DISCUSSION: These results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted

Antenatal care and perinatal outcomes in Kwale district, Kenya

<p>Abstract</p> <p>Background</p> <p>The importance of antenatal care (ANC) for improving perinatal outcomes is well established. However access to ANC in Kenya has hardly changed in the past 20 years. This study aims to identify the determinants of attending ANC and the association between attendance and behavioural and perinatal outcomes (live births and healthy birthweight) for women in the Kwale region of Kenya.</p> <p>Method</p> <p>A Cohort survey of 1,562 perinatal outcomes (response rate 100%) during 2004–05 in the catchment areas for five Ministry of Health dispensaries in two divisions of the Kwale region. The associations between background and behavioural decisions on ANC attendance and perinatal outcomes were explored using univariate analysis and multivariate logistic regression models with backwards-stepwise elimination. The outputs from these analyses were reported as odds ratios (OR) with 95% confidence intervals (CI).</p> <p>Results</p> <p>Only 32% (506/1,562) of women reported having any ANC. Women with secondary education or above (adjusted OR 1.83; 95% CI 1.06–3.15) were more likely to attend for ANC, while those living further than 5 km from a dispensary were less likely to attend (OR 0.29; 95% CI 0.22–0.39). Paradoxically, however, the number of ANC visits increased with distance from the dispensary (OR 1.46; 95% CI 1.33–1.60). Women attending ANC at least twice were more likely to have a live birth (vs. stillbirth) in both multivariate models. Women attending for two ANC visits (but not more than two) were more likely to have a healthy weight baby (OR 4.39; 95% CI 1.36–14.15).</p> <p>Conclusion</p> <p>The low attendance for ANC, combined with a positive relationship between attendance and perinatal outcomes for the women in the Kwale region highlight the need for further research to understand reasons for attendance and non-attendance and also for strategies to be put in place to improve attendance for ANC.</p

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table