Systematic review of the empirical evidence of study publication bias and outcome reporting bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Evidence Focused Social Care: on Target or Off-Side?

As contentions continue to engulf the evidence-based practice (EBP) debate within social care, consensus seems to be gravitating towards the softer term of ‘evidence-aware’ practice, although there is as yet no definitive concept on the horizon. Set against a back-drop of competing ideologies, heavily influenced by the natural sciences, what is at stake is the essence of social work: there is a real danger that social work practice be reduced to mere base elements, which seek to eliminate all notions of uncertainly, so essential and endemic to our social world

Global warming in an independent record of the past 130 years

The thermometer-based global surface temperature time series (GST) commands a prominent role in the evidence for global warming, yet this record has considerable uncertainty. An independent record with better geographic coverage would be valuable in understanding recent change in the context of natural variability. We compiled the Paleo Index (PI) from 173 temperature-sensitive proxy time series (corals, ice cores, speleothems, lake and ocean sediments, historical documents). Each series was normalized to produce index values of change relative to a 1901–2000 base period; the index values were then averaged. From 1880 to 1995, the index trends significantly upward, similar to the GST. Smaller-scale aspects of the GST including two warming trends and a warm interval during the 1940s are also observed in the PI. The PI extends to 1730 with 67 records. The upward trend appears to begin in the early 19th century but the year-to-year variability is large and the 1730–1929 trend is small.

State of the science on controversial topics: missing maxillary lateral incisors - a report of the Angle Society of Europe 2012 meeting

BACKGROUND The optimal long-term management of the congenitally missing maxillary lateral incisor continues to cause controversy within the specialty. The Angle Society of Europe meeting 2012 dedicated a day to address some of the current controversies relating to the management of these missing lateral incisors. FINDINGS The format of the day consisted of morning presentations and afternoon breakout sessions to discuss a variety of questions related to the management of missing lateral incisors. CONCLUSIONS The consensus viewpoint from this day was that the care of patients with congenitally missing lateral incisors is best achieved through a multi-disciplinary approach. The current evidence base is weak, and further well-designed, prospective trials are needed.

State of the science on controversial topics: orthodontic therapy and gingival recession (a report of the Angle Society of Europe 2013 meeting)

BACKGROUND Controversy exists in the literature between the role of orthodontic treatment and gingival recession. Whilst movement of teeth outside the alveolar bone has been reported as a risk factor for gingival recession, others have found no such association. FINDINGS The Angle Society of Europe devoted a study day to explore the evidence surrounding these controversies. The aim of the day was for a panel of experts to evaluate the current evidence base in relation to either the beneficial or detrimental effects of orthodontic treatment on the gingival tissue. CONCLUSIONS There remains a relatively weak evidence base for the role of orthodontic treatment and gingival recession and thus a need to undertake a risk assessment and appropriate consent prior to the commencement of treatment. In further prospective, well designed trials are needed.

Attentional blink and impulsiveness: evidence for higher functional impulsivity in non-blinkers compared to blinkers

The attentional blink (AB) represents a fundamental limit of information processing. About 5-10 % of all subjects, however, do not show the AB. Because of the low base rate of these so-called non-blinkers, studies on mechanisms underlying non-blinkers' absent AB are extremely scant. The few existent studies found non-blinkers to be faster and more efficient in information processing compared to blinkers. A personality trait that has been linked previously to speed and efficiency of information processing as well as to the magnitude of the AB is impulsivity. Therefore, the present study investigated whether 15 non-blinkers and 15 blinkers differed from each other in functional and/or dysfunctional impulsivity. To obtain a better understanding of the underlying processing mechanisms, the P300 component in the event-related potential was recorded during performance on the AB task. Our results indicated higher functional impulsivity in non-blinkers compared to blinkers but no differences between the two groups in dysfunctional impulsivity. As indicated by shorter P300 latency, non-blinkers processed information faster than blinkers after the AB period but slower during the AB period. These speed effects, however, were not associated with functional impulsivity. Thus, impulsivity and speed of information processing appear to represent two rather independent sources for non-blinkers' absent AB

Role of the cytoplasmic domain in Anabaena sensory rhodopsin photocycling: vectoriality of Schiff base deprotonation.

Light-induced electric signals in intact E. coli cells generated by heterologously expressed full-length and C-terminally truncated versions of Anabaena sensory rhodopsin (ASR) demonstrate that the charge movements within the membrane-embedded part of the molecule are stringently controlled by the cytoplasmic domain. In particular, truncation inverts the direction of proton movement during Schiff base deprotonation from outward to cytoplasmic. Truncation also alters faster charge movements that occur before Schiff base deprotonation. Asp(217) as previously shown by FTIR serves as a proton acceptor in the truncated ASR but not in the full-length version, and its mutation to Asn restores the natural outward direction of proton movement. Introduction of a potential negative charge (Ser(86) to Asp) on the cytoplasmic side favors a cytoplasmic direction of proton release from the Schiff base. In contrast, mutation of the counterion Asp(75) to Glu reverses the photocurrent to the outward direction in the truncated pigment, and in both truncated and full-length versions accelerates Schiff base deprotonation more than 10-fold. The communication between the cytoplasmic domain and the membrane-embedded photoactive site of ASR demonstrated here is likely to derive from the receptor's use of a cytoplasmic protein for signal transduction, as has been suggested previously from binding studies.

Evidence for glutamatergic ganglion cells in the avian retina

This dissertation presents structural, immunochemical and neurochemical evidence for glutamatergic retinotectal synaptic transmission, augmenting and extending previous physiological and anatomical studies. The evidence is especially striking when the laminar patterns of ($\sp3$H) L-glutamate receptor binding, ($\sp3$H) L-glutamate high affinity uptake (HAU) and glutamate immunoreactivity (GLIR) of the dorsal tectum are compared. All show high activity in the tectal SGFS, with a peak in the most superficial laminae of SGFS followed by dip in the b-c region, and a second broad peak in deeper SGFS. Uptake and immunoreactivity bear a stronger resemblance to one another than either does to receptor binding, consistent with the fact that HAU and GLIR are localized in the same structures: glutamatergic terminals, intrinsic cell bodies and their processes. Receptor binding, as attested by the lack of enucleation effects, is a marker of postsynaptic receptors. In summary, these results are consistent with the hypothesis that most of the retinal projection to the optic tectum is glutamatergic: (1) A glutamate/aspartate HAU system exists in the superficial laminae, and it is dependent upon an intact retinal input, as shown developmentally and by retinal ablation; (2) Glutamate-like immunoreactivity appears in retinorecipient tectal regions (partially responsive to enucleation), in cell bodies of retinal ganglion cells and displaced ganglion cells, and in a non-tectal ganglion cell projection, the ectomammilary nucleus; (3) Sodium-independent glutamate receptor binding (which remains unchanged by enucleation) is most intense in the retinorecipient regions of the tectum and the ectomammilary nucleus. This binding is pharmacologically typical of a CNS sensory structure, being dominated by the quisqualate/kainate receptor subclass. Thus, as with other sensory systems, a portion of the retinotectal projection has been shown to include glutamatergic afferents with the distribution and properties expected of the primary projection ^

The origin of oriented lakes: evidence from the Bolivian Amazon

The presence of hundreds of rectangular and oriented lakes is one of the most striking characteristics of the Llanos de Moxos (LM) landscape in the Bolivian Amazon. Oriented lakes also occur in the Arctic coastal plains of Russia, Alaska and Canada and along the Atlantic Coastal Plain from northeast Florida to southeast New Jersey and along the coast of northeast Brazil. Many different mechanisms have been proposed for their formation. In the LM, Plafker's (1964) tectonic model, in which subsidence results from the propagation of bedrock faults through the foreland sediments, is the most accepted. However, this model has not been verified. Here, we present new results from stratigraphic transects across the borders of three rectangular and oriented lakes in the LM. A paleosol buried under mid-Holocene sediments is used as a stratigraphic marker to assess the vertical displacement of sediments on both sides of the alleged faults. Our results show that there is no vertical displacement and, therefore, that Plafker's model can be ruled out. We suggest that, among all the proposed mechanisms behind lake formation, the combined action of wind and waves is the most likely. The evidence from the LM provides new hints for the formation of oriented lakes worldwide.

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

Advances in understanding energy consumption behavior and the governance of its change - Outline of an integrated framework

Transforming today’s energy systems in industrialized countries requires a substantial reduction of the total energy consumption at the individual level. Selected instruments have been found to be effective in changing people’s behavior in single domains. However, the so far weak success story on reducing overall energy consumption indicates that our understanding of the determining factors of individual energy consumption as well as of its change is far from being conclusive. Among others, the scientific state of the art is dominated by analyzing single domains of consumption and by neglecting embodied energy. It also displays strong disciplinary splits and the literature often fails to distinguish between explaining behavior and explaining change of behavior. Moreover, there are knowledge gaps regarding the legitimacy and effectiveness of the governance of individual consumption behavior and its change. Against this backdrop, the aim of this paper is to establish an integrated interdisciplinary framework that offers a systematic basis for linking the different aspects in research on energy related consumption behavior, thus paving the way for establishing a better evidence base to inform societal actions. The framework connects the three relevant analytical aspects of the topic in question: (1) It systematically and conceptually frames the objects, i.e. the energy consumption behavior and its change (explananda); (2) it structures the factors that potentially explain the energy consumption behavior and its change (explanantia); (3) it provides a differentiated understanding of change inducing interventions in terms of governance. Based on the existing states of the art approaches from different disciplines within the social sciences the proposed framework is supposed to guide interdisciplinary empirical research.

Long-term outcomes and prognostic factors of skull-base chondrosarcoma patients treated with pencil-beam scanning proton therapy at the Paul Scherrer Institute

BACKGROUND Skull-base chondrosarcoma (ChSa) is a rare disease, and the prognostication of this disease entity is ill defined. METHODS We assessed the long-term local control (LC) results, overall survival (OS), and prognostic factors of skull-base ChSa patients treated with pencil beam scanning proton therapy (PBS PT). Seventy-seven (male, 35; 46%) patients with histologically confirmed ChSa were treated at the Paul Scherrer Institute. Median age was 38.9 years (range, 10.2-70.0y). Median delivered dose was 70.0 GyRBE (range, 64.0-76.0 GyRBE). LC, OS, and toxicity-free survival (TFS) rates were calculated using the Kaplan Meier method. RESULTS After a mean follow-up of 69.2 months (range, 4.6-190.8 mo), 6 local (7.8%) failures were observed, 2 of which were late failures. Five (6.5%) patients died. The actuarial 8-year LC and OS were 89.7% and 93.5%, respectively. Tumor volume > 25 cm(3) (P = .02), brainstem/optic apparatus compression at the time of PT (P = .04) and age >30 years (P = .08) were associated with lower rates of LC. High-grade (≥3) radiation-induced toxicity was observed in 6 (7.8%) patients. The 8-year high-grade TFS was 90.8%. A higher rate of high-grade toxicity was observed for older patients (P = .073), those with larger tumor volume (P = .069), and those treated with 5 weekly fractions (P = .069). CONCLUSIONS This is the largest PT series reporting the outcome of patients with low-grade ChSa of the skull base treated with PBS only. Our data indicate that protons are both safe and effective. Tumor volume, brainstem/optic apparatus compression, and age were prognosticators of local failures.

Single crowns versus conventional fillings for the restoration of root-filled teeth.

BACKGROUND Endodontic treatment involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root-filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite, directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth, and may influence durability and cost. The decision to use a post and core in addition to the crown is clinician driven. The comparative clinical performance of crowns or conventional fillings used to restore root-filled teeth is unknown. This review updates the original, which was published in 2012. OBJECTIVES To assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials. SEARCH METHODS We searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME. We also searched the reference lists of articles and ongoing trials registries.There were no restrictions regarding language or date of publication. The search is up-to-date as of 26 March 2015. SELECTION CRITERIA Randomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth that have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration or indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from the included trial and assessed its risk of bias. We carried out data analysis using the 'treatment as allocated' patient population, expressing estimates of intervention effect for dichotomous data as risk ratios, with 95% confidence intervals (CI). MAIN RESULTS We included one trial, which was judged to be at high risk of performance, detection and attrition bias. The 117 participants with a root-filled, premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. None experienced a catastrophic failure (i.e. when the restoration cannot be repaired), although only 104 teeth were included in the final, three-year assessment. There was no clear difference between the crown and composite group and the composite only group for non-catastrophic failures of the restoration (1/54 versus 3/53; RR 0.33; 95% CI 0.04 to 3.05) or failures of the post (2/54 versus 1/53; RR 1.96; 95% CI 0.18 to 21.01) at three years. The quality of the evidence for these outcomes is very low. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of caries, periodontal health status, and costs. AUTHORS' CONCLUSIONS There is insufficient evidence to assess the effects of crowns compared to conventional fillings for the restoration of root-filled teeth. Until more evidence becomes available, clinicians should continue to base decisions about how to restore root-filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.

Step by step: correcting our mental image of the mušlālu

The mušlālu, which is usually understood to be a step- or ramped gate, has so far rarely been discussed in much detail, even though the texts mentioning it have been known for a long time. This is no doubt because the evidence on which to base both philological and archaeological investigations appears sparse and scattered. Up to now, scholars have tended to focus on specific mušlālu-structures. Consequently, there are as many discussions as there are mušlālu-structures. This article attempts to get a sense of the broader picture by bringing together the philological and archaeological data hitherto available with the aim of discussing the mušlālu as term and structure, clarifying the semantics and reassessing the architectural identifications. We hope to demonstrate that it is actually possible to take the evidence one step further and correct the mušlālu image that prevails.

The Geographic Distribution of the Size and Timing of Monetary Policy Actions

This paper examines the magnitude and timing of the effects of changes in the monetary base on the aggregate and regional changes in bank loans within the United States. We consider both Bureau of Economic Analysis (BEA) regions, and individual states and the District of Columbia for our regional analysis. The empirical analysis provides some insight on the bank-lending channel of monetary policy. We find strong evidence of a 4-quarter lag in the effect of changes in the monetary base on bank loans. That finding proves robust across all regions and nearly all states.