Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6×10²⁰ protons on target

We report on measurements of neutrino oscillation using data from the T2K long-baseline neutrino experiment collected between 2010 and 2013. In an analysis of muon neutrino disappearance alone, we find the following estimates and 68% confidence intervals for the two possible mass hierarchies: Normal Hierarchy: sin²θ₂₃= 0.514+0.055−0.056 and ∆m²_32 = (2.51 ± 0.10) × 10⁻³ eV²/c⁴ Inverted Hierarchy: sin²θ₂₃= 0.511 ± 0.055 and ∆m²_13 = (2.48 ± 0.10) × 10⁻³ eV²/c⁴ The analysis accounts for multi-nucleon mechanisms in neutrino interactions which were found to introduce negligible bias. We describe our first analyses that combine measurements of muon neutrino disappearance and electron neutrino appearance to estimate four oscillation parameters, |∆m^2|, sin²θ₂₃, sin²θ₁₃, δCP , and the mass hierarchy. Frequentist and Bayesian intervals are presented for combinations of these parameters, with and without including recent reactor measurements. At 90% confidence level and including reactor measurements, we exclude the region δCP = [0.15, 0.83]π for normal hierarchy and δCP = [−0.08, 1.09]π for inverted hierarchy. The T2K and reactor data weakly favor the normal hierarchy with a Bayes Factor of 2.2. The most probable values and 68% 1D credible intervals for the other oscillation parameters, when reactor data are included, are: sin²θ₂₃= 0.528+0.055−0.038 and |∆m²_32| = (2.51 ± 0.11) × 10⁻³ eV²/c⁴.

Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis

OBJECTIVE: To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee. Design Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points. MAIN OUTCOME MEASURE: Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at -0.9 cm on a 10 cm visual analogue scale. DATA SOURCES: Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites. Eligibility criteria for selecting studies Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head. Results 10 trials in 3803 patients were included. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was -0.4 cm (95% credible interval -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero. Conclusions Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.

Appropriateness of reporting statistical results in orthodontics: the dominance of P values over confidence intervals

The purpose of this study was to search the orthodontic literature and determine the frequency of reporting of confidence intervals (CIs) in orthodontic journals with an impact factor. The six latest issues of the American Journal of Orthodontics and Dentofacial Orthopedics, the European Journal of Orthodontics, and the Angle Orthodontist were hand searched and the reporting of CIs, P values, and implementation of univariate or multivariate statistical analyses were recorded. Additionally, studies were classified according to the type/design as cross-sectional, case-control, cohort, and clinical trials, and according to the subject of the study as growth/genetics, behaviour/psychology, diagnosis/treatment, and biomaterials/biomechanics. The data were analyzed using descriptive statistics followed by univariate examination of statistical associations, logistic regression, and multivariate modelling. CI reporting was very limited and was recorded in only 6 per cent of the included published studies. CI reporting was independent of journal, study area, and design. Studies that used multivariate statistical analyses had a higher probability of reporting CIs compared with those using univariate statistical analyses. Misunderstanding of the use of P values and CIs may have important implications in implementation of research findings in clinical practice.

High expression of octamer-binding transcription factor 4A, prominin-1 and aldehyde dehydrogenase strongly indicates involvement in the initiation of lung adenocarcinoma resulting in shorter disease-free intervals

The increasing relevance of the cancer stem cell (CSC) hypothesis and the impact of CSC-associated markers in the carcinogenesis of solid tumours may provide potential prognostic implications in lung cancer. We propose that a collective genetic analysis of established CSC-related markers will generate data to better define the role of putative CSCs in lung adenocarcinoma (LAC).

Statistical evaluation of time-dependent metabolite concentrations: estimation of post-mortem intervals based on in situ 1H-MRS of the brain

Knowledge of the time interval from death (post-mortem interval, PMI) has an enormous legal, criminological and psychological impact. Aiming to find an objective method for the determination of PMIs in forensic medicine, 1H-MR spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain metabolite concentrations after death. Following the characterization of newly observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915-920), the full set of acquired spectra was analyzed statistically to provide a quantitative estimation of PMIs with their respective confidence limits. In a first step, analytical mathematical functions are proposed to describe the time courses of 10 metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the inverted functions are used to predict PMIs based on the measured metabolite concentrations. Individual PMIs calculated from five different metabolites are then pooled, being weighted by their inverse variances. The predicted PMIs from all individual examinations in the sheep model are compared with known true times. In addition, four human cases with forensically estimated PMIs are compared with predictions based on single in situ MRS measurements. Interpretation of the individual sheep examinations gave a good correlation up to 250 h post-mortem, demonstrating that the predicted PMIs are consistent with the data used to generate the model. Comparison of the estimated PMIs with the forensically determined PMIs in the four human cases shows an adequate correlation. Current PMI estimations based on forensic methods typically suffer from uncertainties in the order of days to weeks without mathematically defined confidence information. In turn, a single 1H-MRS measurement of brain tissue in situ results in PMIs with defined and favorable confidence intervals in the range of hours, thus offering a quantitative and objective method for the determination of PMIs.

Quantifying the periodicty of Inter Movement Intervals of Leg Movements

ims: Periodic leg movements in sleep (PLMS) are a frequent finding in polysomnography. Most patients with restless legs syndrome (RLS) display PLMS. However, since PLMS are also often recorded in healthy elderly subjects, the clinical significance of PLMS is still discussed controversially. Leg movements are seen concurrently with arousals in obstructive sleep apnoea (OSA) may also appear periodically. Quantitative assessment of the periodicity of LM/PLM as measured by inter movement intervals (IMI) is difficult. This is mainly due to influencing factors like sleep architecture and sleep stage, medication, inter and intra patient variability, the arbitrary amplitude and sequence criteria which tend to broaden the IMI distributions or make them even multi-modal. Methods: Here a statistical method is presented that enables eliminating such effects from the raw data before analysing the statistics of IMI. Rather than studying the absolute size of IMI (measured in seconds) we focus on the shape of their distribution (suitably normalized IMI). To this end we employ methods developed in Random Matrix Theory (RMT). Patients: The periodicity of leg movements (LM) of four patient groups (10 to 15 each) showing LM without PLMS (group 1), OSA without PLMS (group 2), PLMS and OSA (group 3) as well as PLMS without OSA (group 4) are compared. Results: The IMI of patients without PLMS (groups 1 and 2) and with PLMS (groups 3 and 4) are statistically different. In patients without PLMS the distribution of normalized IMI resembles closely the one of random events. In contrary IMI of PLMS patients show features of periodic systems (e.g. a pendulum) when studied in normalized manner. Conclusions: For quantifying PLMS periodicity proper normalization of the IMI is crucial. Without this procedure important features are hidden when grouping LM/PLM over whole nights or across patients. The clinical significance of PLMS might be eluded when properly separating random LM from LM that show features of periodic systems.

Reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors

AIMS Common carotid artery intima-media thickness (CCIMT) is widely used as a surrogate marker of atherosclerosis, given its predictive association with cardiovascular disease (CVD). The interpretation of CCIMT values has been hampered by the absence of reference values, however. We therefore aimed to establish reference intervals of CCIMT, obtained using the probably most accurate method at present (i.e. echotracking), to help interpretation of these measures. METHODS AND RESULTS We combined CCIMT data obtained by echotracking on 24 871 individuals (53% men; age range 15-101 years) from 24 research centres worldwide. Individuals without CVD, cardiovascular risk factors (CV-RFs), and BP-, lipid-, and/or glucose-lowering medication constituted a healthy sub-population (n = 4234) used to establish sex-specific equations for percentiles of CCIMT across age. With these equations, we generated CCIMT Z-scores in different reference sub-populations, thereby allowing for a standardized comparison between observed and predicted ('normal') values from individuals of the same age and sex. In the sub-population without CVD and treatment (n = 14 609), and in men and women, respectively, CCIMT Z-scores were independently associated with systolic blood pressure [standardized βs 0.19 (95% CI: 0.16-0.22) and 0.18 (0.15-0.21)], smoking [0.25 (0.19-0.31) and 0.11 (0.04-0.18)], diabetes [0.19 (0.05-0.33) and 0.19 (0.02-0.36)], total-to-HDL cholesterol ratio [0.07 (0.04-0.10) and 0.05 (0.02-0.09)], and body mass index [0.14 (0.12-0.17) and 0.07 (0.04-0.10)]. CONCLUSION We estimated age- and sex-specific percentiles of CCIMT in a healthy population and assessed the association of CV-RFs with CCIMT Z-scores, which enables comparison of IMT values for (patient) groups with different cardiovascular risk profiles, helping interpretation of such measures obtained both in research and clinical settings.

Reporting of statistical results in prosthodontic and implantology journals: p values or confidence intervals?

PURPOSE Confidence intervals (CIs) are integral to the interpretation of the precision and clinical relevance of research findings. The aim of this study was to ascertain the frequency of reporting of CIs in leading prosthodontic and dental implantology journals and to explore possible factors associated with improved reporting. MATERIALS AND METHODS Thirty issues of nine journals in prosthodontics and implant dentistry were accessed, covering the years 2005 to 2012: The Journal of Prosthetic Dentistry, Journal of Oral Rehabilitation, The International Journal of Prosthodontics, The International Journal of Periodontics & Restorative Dentistry, Clinical Oral Implants Research, Clinical Implant Dentistry and Related Research, The International Journal of Oral & Maxillofacial Implants, Implant Dentistry, and Journal of Dentistry. Articles were screened and the reporting of CIs and P values recorded. Other information including study design, region of authorship, involvement of methodologists, and ethical approval was also obtained. Univariable and multivariable logistic regression was used to identify characteristics associated with reporting of CIs. RESULTS Interrater agreement for the data extraction performed was excellent (kappa = 0.88; 95% CI: 0.87 to 0.89). CI reporting was limited, with mean reporting across journals of 14%. CI reporting was associated with journal type, study design, and involvement of a methodologist or statistician. CONCLUSIONS Reporting of CI in implant dentistry and prosthodontic journals requires improvement. Improved reporting will aid appraisal of the clinical relevance of research findings by providing a range of values within which the effect size lies, thus giving the end user the opportunity to interpret the results in relation to clinical practice.

The effects of type of interval, sensory modality, base duration, and psychophysical task on the discrimination of brief time intervals

The present study was designed to investigate the influences of type of psychophysical task (two-alternative forced-choice [2AFC] and reminder tasks), type of interval (filled vs. empty), sensory modality (auditory vs. visual), and base duration (ranging from 100 through 1,000 ms) on performance on duration discrimination. All of these factors were systematically varied in an experiment comprising 192 participants. This approach allowed for obtaining information not only on the general (main) effect of each factor alone, but also on the functional interplay and mutual interactions of some or all of these factors combined. Temporal sensitivity was markedly higher for auditory than for visual intervals, as well as for the reminder relative to the 2AFC task. With regard to base duration, discrimination performance deteriorated with decreasing base durations for intervals below 400 ms, whereas longer intervals were not affected. No indication emerged that overall performance on duration discrimination was influenced by the type of interval, and only two significant interactions were apparent: Base Duration × Type of Interval and Base Duration × Sensory Modality. With filled intervals, the deteriorating effect of base duration was limited to very brief base durations, not exceeding 100 ms, whereas with empty intervals, temporal discriminability was also affected for the 200-ms base duration. Similarly, the performance decrement observed with visual relative to auditory intervals increased with decreasing base durations. These findings suggest that type of task, sensory modality, and base duration represent largely independent sources of variance for performance on duration discrimination that can be accounted for by distinct nontemporal mechanisms.