Placebo-controlled trials of Chinese herbal medicine and conventional medicine - comparative study

BACKGROUND: Chinese herbal medicine (CHM) is increasingly used in the West, but the evidence on its effectiveness is a matter of debate. We compared the characteristics, study quality and results of clinical trials of CHM and conventional medicine. METHODS: Comparative study of placebo-controlled trials of CHM and conventional medicine. Eleven bibliographic databases and searches by hand of 48 Chinese-language journals. Conventional medicine trials matched for condition and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Trials described as double-blind, with adequate generation of allocation sequence and adequate concealment of allocation, were assumed to be of high quality. Data were analysed using funnel plots and multivariable meta-regression models. RESULTS: 136 CHM trials (119 published in Chinese, 17 published in English) and 136 matched conventional medicine trials (125 published in English) were analysed. The quality of Chinese-language CHM trials tended to be lower than that of English-language CHM trials and conventional medicine trials. Three (2%) CHM trials and 10 (7%) conventional medicine trials were of high quality. In all groups, smaller trials showed more beneficial treatment effects than larger trials. CHM trials published in Chinese showed considerably larger effects than CHM trials published in English (adjusted ratio of ORs 0.29, 95% confidence intervals 0.17-0.52). CONCLUSIONS: Biases are present both in placebo-controlled trials of CHM and conventional medicine, but may be most pronounced in CHM trials published in Chinese-language journals. Only few CHM trials of adequate methodology exist and the effectiveness of CHM therefore remains poorly documented.

fMRI of Emotion

Recent brain imaging work has expanded our understanding of the mechanisms of perceptual, cognitive, and motor functions in human subjects, but research into the cerebral control of emotional and motivational function is at a much earlier stage. Important concepts and theories of emotion are briefly introduced, as are research designs and multimodal approaches to answering the central questions in the field. We provide a detailed inspection of the methodological and technical challenges in assessing the cerebral correlates of emotional activation, perception, learning, memory, and emotional regulation behavior in healthy humans. fMRI is particularly challenging in structures such as the amygdala as it is affected by susceptibility-related signal loss, image distortion, physiological and motion artifacts and colocalized Resting State Networks (RSNs). We review how these problems can be mitigated by using optimized echo-planar imaging (EPI) parameters, alternative MR sequences, and correction schemes. High-quality data can be acquired rapidly in these problematic regions with gradient compensated multiecho EPI or high resolution EPI with parallel imaging and optimum gradient directions, combined with distortion correction. Although neuroimaging studies of emotion encounter many difficulties regarding the limitations of measurement precision, research design, and strategies of validating neuropsychological emotion constructs, considerable improvement in data quality and sensitivity to subtle effects can be achieved. The methods outlined offer the prospect for fMRI studies of emotion to provide more sensitive, reliable, and representative models of measurement that systematically relate the dynamics of emotional regulation behavior with topographically distinct patterns of activity in the brain. This will provide additional information as an aid to assessment, categorization, and treatment of patients with emotional and personality disorders.

Historical weather extremes in the “Twentieth Century Reanalysis”

Meteorological or climatological extremes are rare and hence studying them requires long meteorological data sets. Moreover, for addressing the underlying atmospheric processes, detailed three-dimensional data are desired. Until recently the two requirements were incompatible as long meteorological series were only available for a few locations, whereas detailed 3-dimensional data sets such as reanalyses were limited to the past few decades. In 2011, the “Twentieth Century Reanalysis” (20CR) was released, a 6-hourly global atmospheric data set covering the past 140 years, thus combining the two properties. The collection of short papers in this volume contains case studies of individual extreme events in the 20CR data set. In this overview paper we introduce the first six cases and summarise some common findings. All of the events are represented in 20CR in a physically consistent way, allowing further meteorological interpretations and process studies. Also, for most of the events, the magnitudes are underestimated in the ensemble mean. Possible causes are addressed. For interpreting extrema it may be necessary to address individual ensemble members. Also, the density of observations underlying 20CR should be considered. Finally, we point to problems in wind speeds over the Arctic and the northern North Pacific in 20CR prior to the 1950s.

The Samoa Hurricane, 15-16 March 1889

Analysing historical weather extremes such as the tropical cyclone in Samoa in March 1889 could add to our understanding of extreme events. However, up to now the availability of suitable data was limiting the analysis of historical extremes, particularly in remote regions. The new “Twentieth Century Reanalysis” (20CR), which provides six-hourly, three-dimensional data for the entire globe back to 1871, might provide the means to study this and other early events. While its suitability for studying historical extremes has been analysed for events in the northern extratropics (see other papers in this volume), the representation of tropical cyclones, especially in early times, remains unknown. The aim of this paper is to study to the hurricane that struck Samoa on 15-16 March 1889. We analyse the event in 20CR as well as in contemporary observations. We find that the event is not reproduced in the ensemble mean of 20CR, nor is it within the ensemble spread. We argue that this is due to the paucity of data assimilated into 20CR. A preliminary compilation of historical observations from ships for that period, in contrast, provides a relatively consistent picture of the event. This shows that more observations would be available and implies that future versions of surface-based reanalyses might profit from digitizing further observations in the tropical region.

Absorbable collagen membranes for periodontal regeneration: a systematic review

Guided tissue regeneration (GTR) with bioabsorbable collagen membranes (CM) is commonly used for the treatment of periodontal defects. The objective of this systematic review of randomized clinical trials was to assess the clinical efficacy of GTR procedures with CM, with or without bone substitutes, in periodontal infrabony defects compared with that of open flap debridement (OFD) alone. Primary outcomes were tooth loss and gain in clinical attachment level (CAL). Screening of records, data extraction, and risk-of-bias assessments were performed by two reviewers. Weighted mean differences were estimated by random effects meta-analysis. We included 21 reports on 17 trials. Risk of bias was generally high. No data were available for the primary outcome tooth loss. The summary treatment effect for change in CAL for GTR with CM compared with OFD was 1.58 mm (95% CI, 1.27 to 1.88). Despite large between-trial heterogeneity (I2 = 75%, p < .001), all trials favored GTR over OFD. No differences in treatment effects were detected between trials of GTR with CM alone and trials of GTR with CM in combination with bone substitutes (p for interaction, .31). GTR with CM, with or without substitutes, may result in improved clinical outcomes compared with those achieved with OFD alone. Our findings support GTR with CM for the treatment of infrabony periodontal defects.

Stochastic search for semiparametric linear regression models

This paper introduces and analyzes a stochastic search method for parameter estimation in linear regression models in the spirit of Beran and Millar [Ann. Statist. 15(3) (1987) 1131–1154]. The idea is to generate a random finite subset of a parameter space which will automatically contain points which are very close to an unknown true parameter. The motivation for this procedure comes from recent work of Dümbgen et al. [Ann. Statist. 39(2) (2011) 702–730] on regression models with log-concave error distributions.

Statistical inference for the optimal approximating model

In the setting of high-dimensional linear models with Gaussian noise, we investigate the possibility of confidence statements connected to model selection. Although there exist numerous procedures for adaptive (point) estimation, the construction of adaptive confidence regions is severely limited (cf. Li in Ann Stat 17:1001–1008, 1989). The present paper sheds new light on this gap. We develop exact and adaptive confidence regions for the best approximating model in terms of risk. One of our constructions is based on a multiscale procedure and a particular coupling argument. Utilizing exponential inequalities for noncentral χ2-distributions, we show that the risk and quadratic loss of all models within our confidence region are uniformly bounded by the minimal risk times a factor close to one.

Isospin breaking in pion–deuteron scattering and the pion–nucleon scattering lengths

In recent years, high-accuracy data for pionic hydrogen and deuterium have become the primary source of information on the pion–nucleon scattering lengths. Matching the experimental precision requires, in particular, the study of isospin-breaking corrections both in pion– nucleon and pion–deuteron scattering. We review the mechanisms that lead to the cancellation of potentially enhanced virtual-photon corrections in the pion–deuteron system, and discuss the subtleties regarding the definition of the pion–nucleon scattering lengths in the presence of electromagnetic interactions by comparing to nucleon–nucleon scattering. Based on the p±p channels we find for the virtual-photon-subtracted scattering lengths in the isospin basis a1/2/ g= (170.5±2.0) · 10−3M−1p and a3/2/ g= (−86.5±1.8) · 10−3M−1p .

Epidemiology of Brucellosis and Q Fever in Linked Human and Animal Populations in Northern Togo

BACKGROUND: Although brucellosis (Brucella spp.) and Q Fever (Coxiella burnetii) are zoonoses of global importance, very little high quality data are available from West Africa. METHODS/PRINCIPAL FINDINGS: A serosurvey was conducted in Togo's main livestock-raising zone in 2011 in 25 randomly selected villages, including 683 people, 596 cattle, 465 sheep and 221 goats. Additionally, 464 transhumant cattle from Burkina Faso were sampled in 2012. The serological analyses performed were the Rose Bengal Test and ELISA for brucellosis and ELISA and the immunofluorescence assay (IFA) for Q Fever Brucellosis did not appear to pose a major human health problem in the study zone, with only 7 seropositive participants. B. abortus was isolated from 3 bovine hygroma samples, and is likely to be the predominant circulating strain. This may explain the observed seropositivity amongst village cattle (9.2%, 95%CI:4.3-18.6%) and transhumant cattle (7.3%, 95%CI:3.5-14.7%), with an absence of seropositive small ruminants. Exposure of livestock and people to C. burnetii was common, potentially influenced by cultural factors. People of Fulani ethnicity had greater livestock contact and a significantly higher seroprevalence than other ethnic groups (Fulani: 45.5%, 95%CI:37.7-53.6%; non-Fulani: 27.1%, 95%CI:20.6-34.7%). Appropriate diagnostic test cut-off values in endemic settings requires further investigation. Both brucellosis and Q Fever appeared to impact on livestock production. Seropositive cows were more likely to have aborted a foetus during the previous year than seronegative cows, when adjusted for age. This odds was 3.8 times higher (95%CI: 1.2-12.1) for brucellosis and 6.7 times higher (95%CI: 1.3-34.8) for Q Fever. CONCLUSIONS: This is the first epidemiological study of zoonoses in Togo in linked human and animal populations, providing much needed data for West Africa. Exposure to Brucella and C. burnetii is common but further research is needed into the clinical and economic impact.

Eco-Evolutionary Spatial Dynamics. Rapid Evolution and Isolation Explain Food Web Persistence

One of the current challenges in evolutionary ecology is understanding the long-term persistence of contemporary-evolving predator–prey interactions across space and time. To address this, we developed an extension of a multi-locus, multi-trait eco-evolutionary individual-based model that incorporates several interacting species in explicit landscapes. We simulated eco-evolutionary dynamics of multiple species food webs with different degrees of connectance across soil-moisture islands. A broad set of parameter combinations led to the local extinction of species, but some species persisted, and this was associated with (1) high connectance and omnivory and (2) ongoing evolution, due to multi-trait genetic variability of the embedded species. Furthermore, persistence was highest at intermediate island distances, likely because of a balance between predation-induced extinction (strongest at short island distances) and the coupling of island diversity by top predators, which by travelling among islands exert global top-down control of biodiversity. In the simulations with high genetic variation, we also found widespread trait evolutionary changes indicative of eco-evolutionary dynamics. We discuss how the ever-increasing computing power and high-resolution data availability will soon allow researchers to start bridging the in vivo–in silico gap.

Digital implant impressions with the "Individualized Scanbody Technique" for emergence profile support.

OBJECTIVE The Short Communication presents a clinical case in which a novel procedure--the "Individualized Scanbody Technique" (IST)--was applied, starting with an intraoral digital impression and using CAD/CAM process for fabrication of ceramic reconstructions in bone level implants. MATERIAL AND METHODS A standardized scanbody was individually modified in accordance with the created emergence profile of the provisional implant-supported restoration. Due to the specific adaptation of the scanbody, the conditioned supra-implant soft tissue complex was stabilized for the intraoral optical scan process. Then, the implant platform position and the supra-implant mucosa outline were transferred into the three-dimensional data set with a digital impression system. Within the technical workflow, the ZrO2 -implant-abutment substructure could be designed virtually with predictable margins of the supra-implant mucosa. RESULTS After finalization of the 1-piece screw-retained full ceramic implant crown, the restoration demonstrated an appealing treatment outcome with harmonious soft tissue architecture. CONCLUSIONS The IST facilitates a simple and fast approach for a supra-implant mucosal outline transfer in the digital workflow. Moreover, the IST closes the interfaces in the full digital pathway.

What is the frequency of nerve injuries associated with acetabular fractures?

BACKGROUND Acetabular fractures and surgical interventions used to treat them can result in nerve injuries. To date, only small case studies have tried to explore the frequency of nerve injuries and their association with patient and treatment characteristics. High-quality data on the risk of traumatic and iatrogenic nerve lesions and their epidemiology in relation to different fracture types and surgical approaches are lacking. QUESTIONS/PURPOSES The purpose of this study was to determine (1) the proportion of patients who develop nerve injuries after acetabular fracture; (2) which fracture type(s) are associated with increased nerve injury risk; and (3) which surgical approach was associated with the highest proportion of patients developing nerve injuries using data from the German Pelvic Trauma Registry. Two secondary aims were (4) to assess hospital volume-nerve-injury relationship; and (5) internal data validity. METHODS Between March 2001 and June 2012, 2236 patients with acetabular fractures were entered into a prospectively maintained registry from 29 hospitals; of those, 2073 (92.7%) had complete records on the endpoints of interest in this retrospective study and were analyzed. The neurological status in these patients was captured at their admission and at the discharge. A total of 1395 of 2073 (67%) patients underwent surgery, and the proportions of intervention-related and other hospital-acquired nerve injuries were obtained. Overall proportions of patients developing nerve injuries, risk based on fracture type, and risk of surgical approach type were analyzed. RESULTS The proportion of patients being diagnosed with nerve injuries at hospital admission was 4% (76 of 2073) and at discharge 7% (134 or 2073). Patients with fractures of the "posterior wall" (relative risk [RR], 2.0; 95% confidence interval [CI], 1.4-2.8; p=0.001), "posterior column and posterior wall" (RR, 2.9; CI, 1.6-5.0; p=0.002), and "transverse+posterior wall" fracture (RR, 2.1; CI, 1.3-3.5; p=0.010) were more likely to have nerve injuries at hospital discharge. The proportion of patients with intervention-related nerve injuries and that of patients with other hospital-acquired nerve injuries was 2% (24 of 1395 and 46 of 2073, respectively). They both were associated with the Kocher-Langenbeck approach (RR, 3.0; CI, 1.4-6.2; p=0.006; and RR, 2.4; CI, 1.4-4.3; p=0.004, respectively). CONCLUSIONS Acetabular fractures with the involvement of posterior wall were most commonly accompanied with nerve injuries. The data suggest also that Kocher-Langenbeck approach to the pelvic ring is associated with a higher risk of perioperative nerve injuries. Trauma surgeons should be aware of common nerve injuries, particularly in posterior wall fractures. The results of the study should help provide patients with more exact information on the risk of perioperative nerve injuries in acetabular fractures. LEVEL OF EVIDENCE Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

GOCE: assessment of GPS-only gravity field determination

The GOCE satellite was orbiting the Earth in a Sun-synchronous orbit at a very low altitude for more than 4 years. This low orbit and the availability of high-quality data make it worthwhile to assess the contribution of GOCE GPS data to the recovery of both the static and time-variable gravity fields. We use the kinematic positions of the official GOCE precise science orbit (PSO) product to perform gravity field determination using the Celestial Mechanics Approach. The generated gravity field solutions reveal severe systematic errors centered along the geomagnetic equator. Their size is significantly coupled with the ionospheric density and thus generally increasing over the mission period. The systematic errors may be traced back to the kinematic positions of the PSO product and eventually to the ionosphere-free GPS carrier phase observations used for orbit determination. As they cannot be explained by the current higher order ionospheric correction model recommended by the IERS Conventions 2010, an empirical approach is presented by discarding GPS data affected by large ionospheric changes. Such a measure yields a strong reduction of the systematic errors along the geomagnetic equator in the gravity field recovery, and only marginally reduces the set of useable kinematic positions by at maximum 6 % for severe ionosphere conditions. Eventually it is shown that GOCE gravity field solutions based on kinematic positions have a limited sensitivity to the largest annual signal related to land hydrology.

Magnetic anisotropy in clinopyroxene and orthopyroxene single crystals

Pyroxenes constitute an important component in mafic igneous and metamorphic rocks. They often possess a prismatic habit, and their long axis, the crystallographic c axis, helps define a lineation in a textured rock. Anisotropy of magnetic susceptibility (AMS) serves as a fabric indicator in igneous and metamorphic rocks. If a rock’s AMS is carried by pyroxenes, it can be related to their crystallographic preferred orientation and degree of alignment. This requires knowing the intrinsic AMS of pyroxene single crystals. This study provides a comprehensive low-field and high-field AMS investigation of chemically diverse orthopyroxene and clinopyroxene crystals in relation to crystal structure, chemical composition, oxidation state of Fe, and the possible presence of ferromagnetic inclusions. The paramagnetic anisotropy, extracted from high-field data, shows clear relationships to crystallographic directions and Fe concentration both in clinopyroxene and orthopyroxene. In the diopside-augite series, the intermediate susceptibility is parallel to b, and the maximum is at 45° to the c axis. In aegirine, the intermediate axis remains parallel to b, while the maximum susceptibility is parallel to c. The AMS of spodumene depends on Fe concentration. In enstatite, the maximum susceptibility aligns with c and the minimum with b, and in the case of hypersthene, the maximum susceptibility is normal to the exsolution lamellae. Magnetite inclusions within augite possess a ferromagnetic anisotropy with consistent orientation of the principal susceptibilities, which dominates the low-field anisotropy. These results provide better understanding of magnetic anisotropy in pyroxenes and form a solid basis for interpretation of magnetic fabrics in pyroxene-bearing rocks.

GOCE precise orbit determination for the entire Mission – challenges in the final mission phase

The Gravity field and steady-state Ocean Circulation Explorer (GOCE), ESA’s first Earth Explorer core mission, was launched on March 17, 2009 into a sunsynchronous dusk-dawn orbit and eventually re-entered into the Earth’s atmosphere on November 11, 2013. A precise science orbit (PSO) product was provided by the GOCE High-level Processing Facility (HPF) from the GPS high-low Satellite-to-Satellite Tracking (hl-SST) data from the beginning until the very last days of the mission. We recapitulate the PSO procedure and refer to the results achieved until the official end of the GOCE mission on October 21, 2013, where independent validations with Satellite Laser ranging (SLR) measurements confirmed a high quality of the PSO product of about 2 cm 1-D RMS. We then focus on the period after the official end of the mission, where orbits could still be determined thanks to the continuously running GPS receivers delivering high quality data until a few hours before the re-entry into the Earth’s atmosphere. We address the challenges encountered for orbit determination during these last days and report on adaptions in the PSO procedure to also obtain good orbit results at the unprecedented low orbital altitudes below 224 km.