Individual patient data meta-analysis of diagnostic and prognostic studies in obstetrics, gynaecology and reproductive medicine

BACKGROUND: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine. METHODS/DESIGN: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians. DISCUSSION: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research.

Koproduktion von Wissen in der Entwicklung des Biolandbaus - Einflüsse von Marginalisierung, Anerkennung und Markt

The empirical analysis of the historical development of transdisciplinary co-production of knowledge (CPK) in organic agriculture (OA) in Switzerland has revealed three distinct phases. The initial phase shows various characteristics of transdisciplinary CPK and a high importance of experiential knowledge. The 2nd and 3rd phases involve an in-creasing segregation of farmers’, extension agents’, and scientists’ knowledge, caused by internal and external impacts, i.e. foundation of independent research institutions, changes in agriculture policy, and new market strategies. These developments strikingly represent an ambiguous trend: the growing societal and political recognition of OA and the increasing market, which are positive achievements, are associated by a gradual loss of very precious forms of CPK. A successful re-establishment of CPK processes and re-integration of experiential knowledge would help to resolve this dilemma and thus improve future research in OA and sustainability research in general.

Buttress form of the central African rain forest tree Microberlinia bisulcata, and its possible role in nutrient acquisition

Buttressing is a trait special to tropical trees but explanations for its occurrence remain inconclusive. The two main hypotheses are that they provide structural support and/or promote nutrient acquisition. Studies of the first are common but the second has received much less attention. Architectural measurements were made on adult and juvenile trees of the ectomycorrhizal species Microberlinia bisulcata, in Korup (Cameroon). Buttressing on this species is highly distinctive with strong lateral extension of surface roots of the juveniles leading to a mature buttress system of a shallow spreading form on adults. This contrasts with more vertical buttresses, closer to the stem, found on many other tropical tree species. No clear relationship between main buttress and large branch distribution was found. Whilst this does not argue against the essential structural role of buttresses for these very large tropical trees, the form on M. bisulcata does suggest a likely second role, that of aiding nutrient acquisition. At the Korup site, with its deep sandy soils of very low phosphorus status, and where most nutrient cycling takes place in a thin surface layer of fine roots and mycorrhizas, it appears that buttress form could develop from soil-surface root exploration for nutrients by juvenile trees. It may accordingly allow M. bisulcata to attain the higher greater competitive ability, faster growth rate, and maximum tree size that it does compared with other co-occurring tree species. For sites across the tropics in general, the degree of shallowness and spatial extension of buttresses of the dominant species is hypothesized to increase with decreasing nutrient availability.

Die Inszenierung der Bilder Ephemere Architekturen bei Thomas Demand

In den Arbeiten des Künstlers Thomas Demand sind das Ephemere und das Architektonische eng verzahnt: er baut aufwendige Außen- und Innenräume aus Papier, die ihren temporären Charakter durch materialbedingte Fragilität beweisen, vor allem aber durch die Entscheidung, sie nach der finalen photographischen Aufnahme zu zerstören. Das Ephemere reicht aber auch in die Inszenierung der Bilder bei Ausstellungen hinein. Was als Paragone zwischen der Museumsarchitektur eines Jean Nouvel, Peter Zumthor, Mies van der Rohe und der auszustellenden Kunst beginnt, entwickelt sich zum monumentalen Gesamtkunstwerk, bei dem sich zwischen vorhandener Architektur, Ausstellungsarchitektur und Bildern durch Zitat und mimetischen Eingriff vielfältige Dialoge, aber auch Spannungen ergeben.

Walking a Thin Line: The Regulation of EPGs

The digitisation of television broadcasting has facilitated an exponential growth both in the number and the diversity of programs and channels. Electronic Programme Guides (EPGs) help consumers find their way in this abundance of offerings.EPGs serve as a classical listing magazine or broadcasting guide with extensive information on television programs; like VCRs, they enable the recording of programs; as search engines, they allow users to look for content on the basis of a keyword; and finally, EPGs list the most favoured programs on the first page, either on the basis of popularity, the personal profile of the consumer or on the basis of agreements with particular broadcasting agencies. This article assesses how various European countries approach the regulation of EPGs and determines whether and how they try to reaffirm guarantees for diversity and pluralism in the digital television environment.

Pollen percentage thresholds of Abies alba based on 13-year annual records of pollen deposition in modified Tauber traps: perspectives of application to fossil situations

Abies alba (fir), a submontane tree from Central European mountains and uplands, is of special interest for palaeoecological and palaeoclimate interpretations due to its sensitivity to air and soil humidity. Its present distribution limit in the uplands of SE Poland is still a matter of debate. In the Holocene fir expanded to Poland very late, but early fir populations are supposed to occur in the Šumava Mts (Czech Republic). The study aims: to estimate pollen thresholds for fir presence/absence in Bohemia (Czech Republic) and Poland on the basis of modified Tauber pollen traps; to use these thresholds for tracing fir presence in two pollen diagrams from Poland (Słone and Bezedna lakes) in the border zone between the Roztocze region (with fir forest stands today) and Polesie (where fir has never played an important role); and to investigate how the percentage presence/absence threshold can be used to trace the occurrence and abundance of fir trees in the Šumava Mts based on the pollen diagrams of Rokytecká slat' and Mrtvý luh. The fir pollen thresholds estimated in terms of PAR (pollen accumulation rates or pollen influx) range from 843 (grains cm− 2 year− 1) (Roztocze) to 61 (Krkonoše) and 49 (Šumava). Percentage thresholds range from 0.3% in Krkonoše where fir trees are not present within 4 km to 22% in fir-dominated woodland of the Roztocze, providing evidence of strong underrepresentation of fir in the pollen deposition. Application of these percentage thresholds to the Słone and Bezedna pollen diagrams indicates that occurrence of fir in the region is possible from 3.5 cal ky BP onwards, though the evidence is not decisive. In the Šumava, a low representation of fir pollen (1–2%) reflecting presence of scattered fir trees was detected as early as ca. 7.0 cal ky BP.

The performance of single- and multi-proxy transfer functions (testate amoebae, bryophytes, vascular plants) for reconstructing mire surface wetness and pH

Peatlands are widely exploited archives of paleoenvironmental change. We developed and compared multiple transfer functions to infer peatland depth to the water table (DWT) and pH based on testate amoeba (percentages, or presence/absence), bryophyte presence/absence, and vascular plant presence/absence data from sub-alpine peatlands in the SE Swiss Alps in order to 1) compare the performance of single-proxy vs. multi-proxy models and 2) assess the performance of presence/absence models. Bootstrapping cross-validation showing the best performing single-proxy transfer functions for both DWT and pH were those based on bryophytes. The best performing transfer functions overall for DWT were those based on combined testate amoebae percentages, bryophytes and vascular plants; and, for pH, those based on testate amoebae and bryophytes. The comparison of DWT and pH inferred from testate amoeba percentages and presence/absence data showed similar general patterns but differences in the magnitude and timing of some shifts. These results show new directions for paleoenvironmental research, 1) suggesting that it is possible to build good-performing transfer functions using presence/absence data, although with some loss of accuracy, and 2) supporting the idea that multi-proxy inference models may improve paleoecological reconstruction. The performance of multi-proxy and single-proxy transfer functions should be further compared in paleoecological data.

Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model

The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic β-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis. TNC downregulates Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber formation, activates Wnt signaling, and induces Wnt target genes in tumor and endothelial cells. Our results implicate DKK1 downregulation as an important mechanism underlying TNC-enhanced tumor progression through the provision of a proangiogenic tumor microenvironment.

International palliative care experts' view on phenomena indicating the last hours and days of life

BACKGROUND Providing the highest quality care for dying patients should be a core clinical proficiency and an integral part of comprehensive management, as fundamental as diagnosis and treatment. The aim of this study was to provide expert consensus on phenomena for identification and prediction of the last hours or days of a patient's life. This study is part of the OPCARE9 project, funded by the European Commission's Seventh Framework Programme. METHOD The phenomena associated with approaching death were generated using Delphi technique. The Delphi process was set up in three cycles to collate a set of useful and relevant phenomena that identify and predict the last hours and days of life. Each cycle included: (1) development of the questionnaire, (2) distribution of the Delphi questionnaire and (3) review and synthesis of findings. RESULTS The first Delphi cycle of 252 participants (health care professionals, volunteers, public) generated 194 different phenomena, perceptions and observations. In the second cycle, these phenomena were checked for their specific ability to diagnose the last hours/days of life. Fifty-eight phenomena achieved more than 80% expert consensus and were grouped into nine categories. In the third cycle, these 58 phenomena were ranked by a group of palliative care experts (78 professionals, including physicians, nurses, psycho-social-spiritual support; response rate 72%, see Table 1) in terms of clinical relevance to the prediction that a person will die within the next few hours/days. Twenty-one phenomena were determined to have "high relevance" by more than 50% of the experts. Based on these findings, the changes in the following categories (each consisting of up to three phenomena) were considered highly relevant to clinicians in identifying and predicting a patient's last hours/days of life: "breathing", "general deterioration", "consciousness/cognition", "skin", "intake of fluid, food, others", "emotional state" and "non-observations/expressed opinions/other". CONCLUSION Experts from different professional backgrounds identified a set of categories describing a structure within which clinical phenomena can be clinically assessed, in order to more accurately predict whether someone will die within the next days or hours. However, these phenomena need further specification for clinical use.

The ecological consequences of megafaunal loss: giant tortoises and wetland biodiversity

The giant tortoises of the Galapagos have become greatly depleted since European discovery of the islands in the 16th Century, with populations declining from an estimated 250000 to between 8000 and 14000 in the 1970s. Successful tortoise conservation efforts have focused on species recovery, but ecosystem conservation and restoration requires a better understanding of the wider ecological consequences of this drastic reduction in the archipelago's only large native herbivore. We report the first evidence from palaeoecological records of coprophilous fungal spores of the formerly more extensive geographical range of giant tortoises in the highlands of Santa Cruz Island. Upland tortoise populations on Santa Cruz declined 500-700years ago, likely the result of human impact or possible climatic change. Former freshwater wetlands, a now limited habitat-type, were found to have converted to Sphagnum bogs concomitant with tortoise loss, subsequently leading to the decline of several now-rare or extinct plant species.

Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children

BACKGROUND Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. OBJECTIVES We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). METHODS First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. RESULTS Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). CONCLUSION Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Advancing psychotherapy and evidence-based psychological interventions

Psychological models of mental disorders guide research into psychological and environmental factors that elicit and maintain mental disorders as well as interventions to reduce them. This paper addresses four areas. (1) Psychological models of mental disorders have become increasingly transdiagnostic, focusing on core cognitive endophenotypes of psychopathology from an integrative cognitive psychology perspective rather than offering explanations for unitary mental disorders. It is argued that psychological interventions for mental disorders will increasingly target specific cognitive dysfunctions rather than symptom-based mental disorders as a result. (2) Psychotherapy research still lacks a comprehensive conceptual framework that brings together the wide variety of findings, models and perspectives. Analysing the state-of-the-art in psychotherapy treatment research, “component analyses” aiming at an optimal identification of core ingredients and the mechanisms of change is highlighted as the core need towards improved efficacy and effectiveness of psychotherapy, and improved translation to routine care. (3) In order to provide more effective psychological interventions to children and adolescents, there is a need to develop new and/or improved psychotherapeutic interventions on the basis of developmental psychopathology research taking into account knowledge of mediators and moderators. Developmental neuroscience research might be instrumental to uncover associated aberrant brain processes in children and adolescents with mental health problems and to better examine mechanisms of their correction by means of psychotherapy and psychological interventions. (4) Psychotherapy research needs to broaden in terms of adoption of large-scale public health strategies and treatments that can be applied to more patients in a simpler and cost-effective way. Increased research on efficacy and moderators of Internet-based treatments and e-mental health tools (e.g. to support “real time” clinical decision-making to prevent treatment failure or relapse) might be one promising way forward.

Current role of surgery for high risk prostate cancer

In this review, the role of surgery in patients with adverse tumor characteristics and a high risk of tumor progression are discussed. In the current PSA era the proportion of patients presenting with high risk prostate cancer (PCa) is estimated to be between 15% and 25% with a 10-year cancer specific survival in the range of 80-90% for those receiving active local treatment. The treatment of high risk prostate cancer is a contemporary challenge. Surgery in this group is gaining popularity since 10-year cancer specific survival data of over 90% has been described. Radical prostatectomy should be combined with extended lymphadenectomy. Adjuvant or salvage therapies may be needed in more than half of patients , guided by pathologic findings and postoperative PSA. Unfortunately there are no randomized controlled trials comparing radical prostatectomy to radiotherapy and no single treatment can be universally recommended. This group of high risk prostate cancer patients should be considered a multi-disciplinary challenge; however, for the properly selected patient, radical prostatectomy either as initial or as the only therapy can be considered an excellent treatment.

A test of genetic association among male nuptial coloration, female mating preference, and male aggression bias within a polymorphic population of cichlid fish

Both inter- and intrasexual selection have been implicated in the origin and maintenance of species-rich taxa with diverse sexual traits. Simultaneous disruptive selection by female mate choice and male-male competition can, in theory, lead to speciation without geographical isolation if both act on the same male trait. Female mate choice can generate discontinuities in gene flow, while male-male competition can generate negative frequency-dependent selection stabilizing the male trait polymorphism. Speciation may be facilitated when mating preference and/or aggression bias are physically linked to the trait they operate on. We tested for genetic associations among female mating preference, male aggression bias and male coloration in the Lake Victoria cichlid Pundamilia. We crossed females from a phenotypically variable population with males from both extreme ends of the phenotype distribution in the same population (blue or red). Male offspring of a red sire were significantly redder than males of a blue sire, indicating that intra-population variation in male coloration is heritable. We tested mating preferences of female offspring and aggression biases of male offspring using binary choice tests. There was no evidence for associations at the family level between female mating preferences and coloration of sires, but dam identity had a significant effect on female mate preference. Sons of the red sire directed significantly more aggression to red than blue males, whereas sons of the blue sire did not show any bias. There was a positive correlation among individuals between male aggression bias and body coloration, possibly due to pleiotropy or physical linkage, which could facilitate the maintenance of color polymorphism.

Low single dose gabapentin does not affect prefrontal and occipital gamma-aminobutyric acid concentrations

The γ-aminobutyric acid (GABA) system has been proposed as a target for novel antidepressant and anxiolytic treatments. Emerging evidence suggests that gabapentin (GBP), an anticonvulsant drug that significantly increases brain GABA levels, is effective in the treatment of anxiety disorders. The current study was designed to measure prefrontal and occipital GABA levels in medication-free healthy subjects after taking 0 mg, 150 mg and 300 mg GBP. Subjects were scanned on a 3T scanner using a transmit-receive head coil that provided a relatively homogenous radiofrequency field to obtain spectroscopy measurement in the medial prefrontal (MPFC) and occipital cortex (OCC). There was no dose-dependent effect of GBP on GABA levels in the OCC or MPFC. There was also no effect on Glx, choline or N-acetyl-aspartate concentrations. The previously reported finding of increased GABA levels after GBP treatment is not evident for healthy subjects at the dose of 150 and 300 mg. As a result, if subjects are scanned on a 3T scanner, low dose GPB is not useful as an experimental challenge agent on the GABA system.