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A sharper Bonferroni procedure for multiple tests of significance is derived. This procedure is an improvement of Hochberg's (1988) procedure which contrasts the individual P-values with corresponding critical points. It is shown that Hochberg's original procedure is conservative, and can be made more powerful by enlarging the rejection region so that the type-one error is exactly at the nominal level. It is also shown that the modified procedure retains all the desired properties of the original procedure.

It is suggested that the multiple samples in a correlation map or a set of correlation maps should be examined with significance tests as per the Bernoulli probability model. Therefore, both the contemporaneous and lag correlations of summertime precipitation R in any one of the three regions of Northern China （NC）, the Changjiang-Huaihe River Valley （CHRV）, and Southern China （SC） with the SSTA in the global domain have been tested in the present article, using our significance test method and the method proposed by Livezey and Chen （1983） respectively. Our results demonstrate that the contemporaneous correlations of sum- mer R in CHRV with the SSTA are larger than those in NC. Significant correlations of SSTA with CHRV R are found to be in some warm SST regions in the tropics, whereas those of SSTA with NC R, which are opposite in sign as compared to the SSTA-CHRVR correlations, are found to be in some regions where the mean SSTs are low. In comparison with the patterns of the contemporaneous correlations, the 1 to 12 month lag correlations between NC R and SSTA, and those between CHRV summer R and SSTA show similar patterns, including the magnitudes and signs, and the spatial distributions of the coefficients. However, the summer rainfall in SC is not well correlated with the SSTA, no matter how long the lag interval is. The results derived from the observations have set up a relationship frame connecting the precipitation anomalies in NC, CHRV, and SC with the SSTA in the global domain, which is critically useful for our understanding and predicting the climate variabilities in different parts of China. Both NC and CHRV summer R are connected with E1 Nifio events, showing a ‘- -＇pattern in an E1 Nifio year and a‘＋ ＋＇ pattern in the subsequent year. Key words summer precipitation; eastern China; global sea surface

Nowadays applied work in business and economics requires a solid understanding of econometric methods to support decision-making. Combining a solid exposition of econometric methods with an application-oriented approach, this rigorous textbook provides students with a working understanding and hands-on experience of current econometrics. Taking a 'learning by doing' approach, it covers basic econometric methods (statistics, simple and multiple regression, nonlinear regression, maximum likelihood, and generalized method of moments), and addresses the creative process of model building with due attention to diagnostic testing and model improvement. Its last part is devoted to two major application areas: the econometrics of choice data (logit and probit, multinomial and ordered choice, truncated and censored data, and duration data) and the econometrics of time series data (univariate time series, trends, volatility, vector autoregressions, and a brief discussion of SUR models, panel data, and simultaneous equations). · Real-world text examples and practical exercise questions stimulate active learning and show how econometrics can solve practical questions in modern business and economic management. · Focuses on the core of econometrics, regression, and covers two major advanced topics, choice data with applications in marketing and micro-economics, and time series data with applications in finance and macro-economics. · Learning-support features include concise, manageable sections of text, frequent cross-references to related and background material, summaries, computational schemes, keyword lists, suggested further reading, exercise sets, and online data sets and solutions. · Derivations and theory exercises are clearly marked for students in advanced courses. This textbook is perfect for advanced undergraduate students, new graduate students, and applied researchers in econometrics, business, and economics, and for researchers in other fields that draw on modern applied econometrics.

This paper introduces the model confidence set (MCS) and applies it to the selection of models. A MCS is a set of models that is constructed such that it will contain the best model with a given level of confidence. The MCS is in this sense analogous to a confidence interval for a parameter. The MCS acknowledges the limitations of the data, such that uninformative data yield a MCS with many models, whereas informative data yield a MCS with only a few models. The MCS procedure does not assume that a particular model is the true model; in fact, the MCS procedure can be used to compare more general objects, beyond the comparison of models. We apply the MCS procedure to two empirical problems. First, we revisit the inflation forecasting problem posed by Stock and Watson (1999), and compute the MCS for their set of inflation forecasts. Second, we compare a number of Taylor rule regressions and determine the MCS of the best regression in terms of in-sample likelihood criteria.

ObjectivesThis study aims to define consensus-based criteria for acquiring and reporting prostate MRI and establishing prerequisites for image quality.MethodsA total of 44 leading urologists and urogenital radiologists who are experts in prostate cancer imaging from the European Society of Urogenital Radiology (ESUR) and EAU Section of Urologic Imaging (ESUI) participated in a Delphi consensus process. Panellists completed two rounds of questionnaires with 55 items under three headings: image quality assessment, interpretation and reporting, and radiologists’ experience plus training centres. Of 55 questions, 31 were rated for agreement on a 9-point scale, and 24 were multiple-choice or open. For agreement items, there was consensus agreement with an agreement ≥ 70% (score 7–9) and disagreement of ≤ 15% of the panellists. For the other questions, a consensus was considered with ≥ 50% of votes.ResultsTwenty-four out of 31 of agreement items and 11/16 of other questions reached consensus. Agreement statements were (1) reporting of image quality should be performed and implemented into clinical practice; (2) for interpretation performance, radiologists should use self-performance tests with histopathology feedback, compare their interpretation with expert-reading and use external performance assessments; and (3) radiologists must attend theoretical and hands-on courses before interpreting prostate MRI. Limitations are that the results are expert opinions and not based on systematic reviews or meta-analyses. There was no consensus on outcomes statements of prostate MRI assessment as quality marker.ConclusionsAn ESUR and ESUI expert panel showed high agreement (74%) on issues improving prostate MRI quality. Checking and reporting of image quality are mandatory. Prostate radiologists should attend theoretical and hands-on courses, followed by supervised education, and must perform regular performance assessments.Key Points• Multi-parametric MRI in the diagnostic pathway of prostate cancer has a well-established upfront role in the recently updated European Association of Urology guideline and American Urological Association recommendations.• Suboptimal image acquisition and reporting at an individual level will result in clinicians losing confidence in the technique and returning to the (non-MRI) systematic biopsy pathway. Therefore, it is crucial to establish quality criteria for the acquisition and reporting of mpMRI.• To ensure high-quality prostate MRI, experts consider checking and reporting of image quality mandatory. Prostate radiologists must attend theoretical and hands-on courses, followed by supervised education, and must perform regular self- and external performance assessments.

Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07–5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45–2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.

Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects. BI-505 was well tolerated in an earlier phase 1 trial. In this phase 2 trial the effects of BI-505 in patients with SMM were studied. Four patients were enrolled and three of them completed the first cycle of treatment defined as 5 doses of BI-505, a total of 43 mg/kg BW, over a 7-week period. In the three evaluable patients, BI-505 showed a benign safety profile. None of the patients achieved a response as defined per protocol. EudraCT number: 2012-004884-29. The study was conducted to assess the efficacy, safety and pharmacodynamics of BI-505 in patients with SMM. BI-505 showed no clinically relevant efficacy on disease activity in these patients with SMM, even if well tolerated. ClinicalTrials.gov Identifier: NCT01838369.

ObjectivesTo explore which preoperative clinical data and conventional MRI findings may indicate microvascular invasion (MVI) of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and have clinical significance.MethodsThe study enrolled 113 patients with histopathologically confirmed cHCC-CCA (MVI-positive group [n = 56], MVI-negative group [n = 57]). Two radiologists retrospectively assessed the preoperative MRI features (qualitative analysis of morphology and dynamic enhancement features), and each lesion was assigned according to the LI-RADS. Preoperative clinical data were also evaluated. Logistic regression analyses were used to assess the relative value of these parameters as potential predictors of MVI. Recurrence-free survival (RFS) rates after hepatectomy in the two groups were estimated using Kaplan–Meier survival curves and compared using the log-rank test.ResultsThe majority of cHCC-CCAs were categorized as LR-M. On multivariate analysis, a higher serum AFP level (OR, 0.523; 95% CI, 0.282–0.971; p = 0.040), intratumoral fat deposition (OR, 14.368; 95% CI, 2.749–75.098; p = 0.002), and irregular arterial peritumoral enhancement (OR, 0.322; 95% CI, 0.164–0.631; p = 0.001) were independent variables associated with the MVI of cHCC-CCA. After hepatectomy, patients with MVI of cHCC-CCA showed earlier recurrence than those without MVI (hazard ratio [HR], 0.402; 95% CI, 0.189–0.854, p = 0.013).ConclusionA higher serum AFP level and irregular arterial peritumoral enhancement are potential predictive biomarkers for the MVI of cHCC-CCA, while intratumoral fat detected on MRI suggests a low risk of MVI. Furthermore, cHCC-CCAs with MVI may have worse surgical outcomes with regard to early recurrence than those without MVI.Key Points• Higher serum levels of AFP combined with irregular arterial peritumoral enhancement are independent risk factors for the MVI of cHCC-CCA, while fat deposition might be a protective factor.• cHCC-CCA with MVI may have a higher risk of early recurrence after surgery.• Most cHCC-CCAs were categorized as LR-M in this study, and no significant difference was found in MVI based on LI-RADS category.

Studies of executive function (EF) in autism spectrum disorder (ASD) have reported mixed findings. Possible confounds include EF domain assessed and co-occurring neurodevelopmental diagnoses. EF task performance across multiple domains and everyday function of autistic adults (n = 110) was significantly different to age- and IQ-matched controls (n = 31). Although significantly more likely to fall into the clinically impaired range, 35.8% of the ASD group showed no impairment on EF measures. Factor analysis revealed a single unifying EF construct rather than a selective pattern of impairment. Dysexecutive behaviours were frequently reported in the ASD group, unrelated to Autism symptoms, EF task performance or co-occurring conditions. This study suggests autistic adults can experience clinically significant executive function difficulties and co-occuring dysexecutive behaviours that are disabling in everyday life.