Reporting of methodologic information on trial registries for quality assessment: a study of trial records retrieved from the WHO search portal

Background: Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results. Methods and Findings: The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaboration’s ‘Risk of bias’ tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0–8.4%), 1.4% (0–2.8%), 41% (35–47%), 8.4% (4.1–13%), and 66% (60–72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows: eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions (53%) and sample size calculation (1%). Conclusions: Trial registries currently contain limited methodologic information about registered RCTs. In order to permit adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available.

In search for better pharmacological prophylaxis for acute mountain sickness: looking in other directions.

Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response. Starting off from the opposite hypothesis that AMS may be caused by an initial excessive response to hypoxia, we suggest that directly or indirectly blunting-specific parts of the response might provide promising research alternatives. This reasoning is based on the observations that (i) humans, once acclimatized, can climb Mt Everest experiencing arterial partial oxygen pressures (PaO2 ) as low as 25 mmHg without AMS symptoms; (ii) paradoxically, AMS usually develops at much higher PaO2 levels; and (iii) several biomarkers, suggesting initial activation of specific pathways at such PaO2 , are correlated with AMS. Apart from looking for substances that stimulate certain hypoxia triggered effects, such as the ventilatory response to hypoxia, we suggest to also investigate pharmacological means aiming at blunting certain other specific hypoxia-activated pathways, or stimulating their agonists, in the quest for better pharmacological prophylaxis for AMS.

KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype.

To characterise the genetics of splenic marginal zone lymphoma (SMZL), we performed whole exome sequencing of 16 cases and identified novel recurrent inactivating mutations in Kruppel-like factor 2 (KLF2), a gene whose deficiency was previously shown to cause splenic marginal zone hyperplasia in mice. KLF2 mutation was found in 40 (42%) of 96 SMZLs, but rarely in other B-cell lymphomas. The majority of KLF2 mutations were frameshift indels or nonsense changes, with missense mutations clustered in the C-terminal zinc finger domains. Functional assays showed that these mutations inactivated the ability of KLF2 to suppress NF-κB activation by TLR, BCR, BAFFR and TNFR signalling. Further extensive investigations revealed common and distinct genetic changes between SMZL with and without KLF2 mutation. IGHV1-2 rearrangement and 7q deletion were primarily seen in SMZL with KLF2 mutation, while MYD88 and TP53 mutations were nearly exclusively found in those without KLF2 mutation. NOTCH2, TRAF3, TNFAIP3 and CARD11 mutations were observed in SMZL both with and without KLF2 mutation. Taken together, KLF2 mutation is the most common genetic change in SMZL and identifies a subset with a distinct genotype characterised by multi-genetic changes. These different genetic changes may deregulate various signalling pathways and generate cooperative oncogenic properties, thereby contributing to lymphomagenesis.

Anther culture properties of oat x wild red oat progenies and a search for RAPD markers associated with anther culture ability

Selostus: Ponsiviljeltävyys ja siihen liittyvät geenimerkit peltokauran ja susikauran risteytysjälkeläisissä

Investigation of business models of free zones and possible implications in South East Finland

Tutkielma tarkastelee vapaa alue konseptia osana yritysten kansainvälistä toimitusketjua. Tarkoituksena on löytää keinoja, millä tavoin vapaa alueen houkuttelevuutta voidaan lisätä yritysten näkökulmasta ja millaista liiketoimintaa yritysten on vapaa alueella mahdollista harjoittaa. Tutkielmassa etsitään tekijöitä, jotka vaikuttavat vapaa alueen menestykseen ja jotka voisivat olla sovellettavissa Kaakkois-Suomen ja Venäjän raja-alueelle ottaen huomioon vallitsevat olosuhteet ja lainsäädäntö rajoittavina tekijöinä. Menestystekijöitä ja liiketoimintamalleja haetaan tutkimalla ja analysoimalla lyhyesti muutamia olemassa olevia ja toimivia vapaa alueita. EU tullilain harmonisointi ja kansainvälisen kaupan vapautuminen vähentää vapaa alueen perinteistä merkitystä tullivapaana alueena. Sen sijaan vapaa alueet toimivat yhä enenevissä määrin logistisina keskuksina kansainvälisessä kaupassa ja tarjoavat palveluita, joiden avulla yritykset voivat parantaa logistista kilpailukykyään. Verkostoituminen, satelliitti-ratkaisut ja yhteistoiminta ovat keinoja, millä Kaakkois-Suomen alueen eri logistiikkapalvelujen tarjoajat voivat parantaa suorituskykyään ja joustavuutta kansainvälisessä toimitusketjussa.

All-sky search algorithms for monochromatic signals in bar gravitational wave detector data

In this paper we design and develop several filtering strategies for the analysis of data generated by a resonant bar gravitational wave (GW) antenna, with the goal of assessing the presence (or absence) therein of long-duration monochromatic GW signals, as well as the eventual amplitude and frequency of the signals, within the sensitivity band of the detector. Such signals are most likely generated in the fast rotation of slightly asymmetric spinning stars. We develop practical procedures, together with a study of their statistical properties, which will provide us with useful information on the performance of each technique. The selection of candidate events will then be established according to threshold-crossing probabilities, based on the Neyman-Pearson criterion. In particular, it will be shown that our approach, based on phase estimation, presents a better signal-to-noise ratio than does pure spectral analysis, the most common approach.