Replicability of simulation studies for the investigation of statistical methods: the RepliSims project.

Results of simulation studies evaluating the performance of statistical methods can have a major impact on the way empirical research is implemented. However, so far there is limited evidence of the replicability of simulation studies. Eight highly cited statistical simulation studies were selected, and their replicability was assessed by teams of replicators with formal training in quantitative methodology. The teams used information in the original publications to write simulation code with the aim of replicating the results. The primary outcome was to determine the feasibility of replicability based on reported information in the original publications and supplementary materials. Replicasility varied greatly: some original studies provided detailed information leading to almost perfect replication of results, whereas other studies did not provide enough information to implement any of the reported simulations. Factors facilitating replication included availability of code, detailed reporting or visualization of data-generating procedures and methods, and replicator expertise. Replicability of statistical simulation studies was mainly impeded by lack of information and sustainability of information sources. We encourage researchers publishing simulation studies to transparently report all relevant implementation details either in the research paper itself or in easily accessible supplementary material and to make their simulation code publicly available using permanent links.

Evaluation of the clinical benefits of nanoparticle albumin-bound paclitaxel in women with metastatic breast cancer in British Columbia.

BACKGROUND: Altered formulations of taxanes may lack cross-resistance with standardly used solvent-based taxanes. The primary objective of the present study was to assess the clinical benefit of nanoparticle albumin-bound (nab)-paclitaxel in women with metastatic breast cancer previously treated with and without adjuvant taxane in British Columbia. METHODS: The BC Cancer Agency Pharmacy data repository and Breast Cancer Outcomes Unit database were linked to identify all patients who received nab-paclitaxel in British Columbia since its introduction in 2007. Hormone receptor status, demographic characteristics, number of cycles prescribed, and time to treatment failure were extracted and analyzed. RESULTS: From 2007 to 2011, 138 patients in British Columbia received nab-paclitaxel, with 122 patients available for analysis. Most (70.5%) received adjuvant chemotherapy; about a quarter (24.6%) received an adjuvant taxane. Patients who received adjuvant taxane were more likely to have node-positive (86.7% vs. 48.9%, p = 0.007), estrogen receptor-negative (46.7% vs. 13.0% p < 0.001) disease and to receive initial adjuvant radiotherapy (76.7% vs. 51.1%, p < 0.001). For the entire cohort, the median number of nab-paclitaxel cycles prescribed was 4.4 (range: 0.3-13). The median number of nab-paclitaxel cycles was greater when that agent was given as first- or second-line therapy than as third-line or greater therapy (5.0 cycles vs. 3.7 cycles respectively). The median time to treatment failure was 96 days in the prior adjuvant taxane group (range: 0-361) and 73.5 days in the no prior adjuvant taxane group (range: 0-1176). CONCLUSIONS: This retrospective study demonstrates potential clinical activity of nab-paclitaxel in metastatic breast cancer regardless of whether patients had prior exposure to adjuvant taxanes.

Thromboembolic events associated with immunoglobulin treatment.

OBJECTIVE: Due to an increasing number of reported thromboembolic events (TEE) after the administration of one intravenous immunoglobulin (IVIG) and one subcutaneous immunoglobulin (SCIG), pharmacovigilance and laboratory data were collected to analyse the root cause and assess the reporting frequency of TEEs for various IG products. METHODS: Paul-Ehrlich-Institut retrospectively analysed 228 reports of TEEs associated with six different IG products and estimated annual TEE-reporting rates based on worldwide sale figures over a period of 6 years (2006-2011). In addition, non-activated partial thromboplastin time (NAPTT) testing was performed to capture pro-coagulant potential of six IG products (four IVIG and two SCIG). RESULTS: For three IVIGs, the drug-related TEE-reporting rates remained stable from 2006 to 2011 (0-0·83 cases per 1000 kg IVIG distributed). In contrast, the TEE rate of one IVIG increased significantly from 0·33 cases in 2006 to nearly nine cases in 2010 (P < 0·001). The NAPTT testing of IG products with a low TEE rate revealed a NAPTT time >200 s and a NAPTT ratio >0·8, whereas TEE-associated batches of IG products with an increased TEE rate had a NAPTT ratio <0·8. After modifications of manufacturing processes, a normalization of NAPTT results and a decrease in TEE rates could be demonstrated.

Benefit of transfusion-related acute lung injury risk-minimization measures--German haemovigilance data (2006-2010).

OBJECTIVE: Based on the frequency of immune-mediated and non-immune-mediated transfusion-related acute lung injury (TRALI), the effect of risk-minimization measures was evaluated during a period of 5 years (2006-2010). Risk-minimization measures were implemented in 2008/2009, consisting of exclusion of female donors with a history of pregnancy or exclusion of female donors with human leucocyte antigen (HLA)/human neutrophil alloantigen (HNA) antibodies. METHODS: TRALI was confirmed according to the criteria of the International Haemovigilance Network. Based upon the results of donor testing of white-blood-cell antibodies (WBC-Ab) against HLA or HNAs, confirmed cases were classified as immune- or non-immune-mediated TRALI. Reporting rates were calculated on the basis of the annually transfused blood components, and pre- and post-implementation periods were compared. RESULTS: In total, 60 immune-mediated (75%) and 20 non-immune-mediated (25%) TRALI reactions were confirmed. A total of 68 (64 women and four men) donors were involved: seven red-blood-cell concentrates donors (13%), six platelet concentrate donors (10%), and 48 fresh frozen plasma (FFP) donors (77%). The reporting rate of immune-mediated TRALI caused by FFP decreased continuously; from 12·71 per million units in 2006/2007 to 6·81 per million units in 2008/2009 and no case in 2010. CONCLUSION: The comparison of the pre- and the post-implementation period demonstrated a significantly reduced risk of TRALI events comparing 2006/2007 with 2010 (P-value: <0·01). Furthermore, no case of TRALI-induced fatality occurred after the implementation of risk-minimization measures.

[Evaluation of measures aimed to reduce serious adverse transfusion reactions (hemovigilance data from 1997 to 2008)]. / Bewertung der Massnahmen zur Reduktion schwerwiegender Transfusionsreaktionen (Hämovigilanzdaten von 1997 bis 2008).

On the basis of reports of serious transfusion reactions, measures aimed to improve the safety standard of the manufacturing process of blood components were evaluated from 1997-2008. Measures of the Paul-Ehrlich-Institut (PEI) as well as recommendations of the Advisory Committee "Blood" were considered. Reporting frequencies before and after the implementation of measures were compared. After the implementation of NAT pool testing, a reduction of virus transmission was seen for red blood cell concentrates (RBC) from 1.0/10(6) to 0.5/10(6) units and for platelet concentrates (PC) from 3.0/10(6) to 0.0/10(6) units. After the implementation of a pre-donation sampling, however, no reduction of bacterial infections associated with PC administration (>9.0/10(6)) was identified. To reduce the frequency of TRALI associated with FFP administration (11.2/10(6) units), the use of plasma from male donors or female donors without a history of pregnancy was established in September 2009. Without specific measures of risk reduction, the reporting frequency of severe allergic transfusion reaction increased for all blood components during the investigation period (from 0.8/10(6) to 6.2/10(6) RBC units). The benefit of measures to improve safety standards should be evaluated repeatedly by collecting precise hemovigilance data.

Digestibilidade da silagem de grãos úmidos de milho com diferentes granulometrias para suínos / Digestibility of high moisture corn grain silage with different particle size for swines

Avaliou-se a composição química e determinaram-se os valores de energia digestível (ED) e metabolizável (EM), os coeficientes de digestibilidade da matéria seca (CDMS), da proteína bruta (CDPB), da matéria mineral (CDMM); do extrato etéreo (CDEE); da fibra bruta (CDFB), da energia bruta (CDEB) e do extrativo não nitrogenado (CDENN) e os coeficientes de digestibilidade (CDEB) e metabolizabilidade da energia bruta (CMEB) da silagem de grãos úmidos de milho (SGUM). Foram utilizados 20 suínos, com peso vivo inicial de 28,89±4,9kg, distribuídos em gaiolas de metabolismo. Foi utilizada uma única SGUM, com quatro diferentes granulometrias 513, 587, 717 e 1363µm, que substituiu em 30 por cento a dieta-referência. Os CDMS, CDPB, CDEE, CDMM e CDENN diminuíram com o aumento da granulometria da SGUM. Os CDEB e CMEB também diminuíram de 89,0 para 94,3 por cento, e de 82,9 para 88,5 por cento, respectivamente. Os valores energéticos variaram de 4439 a 4493kcal EB/kg, de 3999 a 4194kcal ED/kg e de 3729 a 3939kcal EM/kg, na matéria seca. Os CDEB e CMEB se reduziram até os diâmetros geométricos médios de 754 e 831µm, respectivamente. A digestibilidade dos nutrientes da SGUM foi influenciada negativamente ao se aumentar o diâmetro geométrico médio das partículas.

The chemical composition; the values of digestible (DE) and metabolizable (ME) energy; the coefficients of digestibility of dry matter (CDDM), crude protein (CDCP), mineral matter (CDMM), ether extract (CDEE), crude fiber (CDFB), crude energy (CDCE), and non nitrogen extractive (CDENN); as well as the coefficient of metabolizability of gross energy (CMGE) of high moisture corn grain silage (HMCGS) were evaluated. Twenty swines, averaging 28.89±4.9kg of live weight, randomly allotted in metabolism cages were used. HMCGS with different particle sizes 513, 587, 717, and 1363µm, replacing 30 percent of basal diet was used. CDDM, CDCP, CDEE, CDMM, and CDENN decreased as the particle size of the HMCGS increased. CDGE and CMGE also decreased from 89.0 to 94.3 percent and from 82.9 to 88.5 percent, respectively. The energy values varied from 4,439 to 4,493kcal of GE/kg, 3,999 to 4,194kcal DE/kg, and 3,729 to 3,939kcal ME/kg, in dry matter basis. CDGE and CMGE decreased until the medium geometric diameters of 754 and 831µm, respectively, and the digestibility of the nutrients of the HMCGS was negatively influenced as the medium geometric diameter of the particles increased.

The German Haemovigilance System--reports of serious adverse transfusion reactions between 1997 and 2007.

Data of the German Haemovigilance System were collected from 1997 to 2007 and assessed on the basis of pre-defined safety standards. Suspected cases of serious adverse reactions following transfusions reported to the Paul-Ehrlich-Institut were evaluated on the basis of national criteria, and the definitions of International Society of Blood Transfusion (ISBT) in compliance with defined causality criteria. The suspected cases were rated as confirmed and unconfirmed transfusion reactions. Assessment of causality took into consideration the clinical course of the adverse reaction and, if necessary, information about donation and manufacturing. Of the 5128 suspected serious adverse reactions, 1603 could be confirmed. Referring to the absolute figures, acute transfusion reactions (e.g. allergic reactions, hypotension and dyspnoea) were recorded most frequently, followed by transfusion-related acute lung injury (TRALI), haemolytic reactions, transfusion-related bacterial infections and virus infections. The majority of the 52 transfusion-related fatalities (14 each) were due to TRALI and acute transfusion reactions (mostly severe allergic reactions). Referred to the blood products administered, immune TRALI cases and TRALI-related fatal courses were most frequently reported after administration of fresh frozen plasma (FFP) (15/10(6) and 3.5/10(6) units, respectively), transfusion-related bacterial infections after administration of platelet concentrates (7/10(6) units), acute haemolytic transfusion reactions after administration of red blood cell concentrates (2.3/10(6)units) and acute transfusion reactions after administration of red blood cell or platelet concentrates (7.8/10(6) and 13/10(6) units, respectively). Despite the high safety standard required for blood products in Germany, there is still room for reducing the frequency of isolated cases of transfusion reactions by targeted action.

Flatland optics. III. Achromatic diffraction.

In the previous two sections of "Flatland optics" [J. Opt. Soc. Am. A 17, 1755 (2000); 18, 1056 (2001)] we described the basic principles of two-dimensional (2D) optics and showed that a wavelength lambda in three-dimensional (3D) space (x, y, z) may appear in Flatland (x, z) as a wave with another wavelength Lambda=lambda/cos alpha. The tilt angle alpha can be modified by a 3D-Spaceland individual, who then is able to influence the 2D optics in a way that must appear to be magical to 2D-Flatland individuals-in the spirit of E. A. Abbott's science fiction story of 1884 [Flatland, a Romance of Many Dimensions, 6th ed. (Dover, New York, 1952)]. Here we show how the light from a white source can be perceived in Flatland as perfectly monochromatic, so diffraction with white light will be free of color blurring and the contrast of interference fringes can be 100%. The basic considerations for perfectly achromatic diffraction are presented, along with experimental illustration of Talbot self-imaging performed with broadband illumination.

Flatland optics. II. Basic experiments.

In "Flatland optics: fundamentals" [J. Opt. Soc. Am. A 17, 1755 (2000)] we described the basic principles of two-dimensional (2D) optics and showed that a wavelength lambda in three-dimensional (3D) space (x,y,z) may appear in Flatland (x,z) as a wave with another wavelength, lambda = lambda/cosalpha. The tilt angle alpha can be modified by a 3D (Spaceland) individual who then is able to influence the 2D optics in a way that must appear to be magical to 2D Flatland individuals-in the spirit of E. A. Abbott's science fiction story [Flatland, a Romance of Many Dimensions, 6th ed. (Dover, New York, 1952)] of 1884. We now want to establish the reality or objectivity of the 2D wavelength lambda by some basic experiments similar to those that demonstrated roughly 200 years ago the wave nature of light. Specifically, we describe how to measure the 2D wavelength lambda by mean of five different arrangements that involve Young's biprism configuration, Talbot's self-imaging effect, measuring the focal length of a Fresnel zone plate, and letting light be diffracted by a double slit and by a grating. We also performed experiments with most of these arrangements. The results reveal that the theoretical wavelength, as predicted by our Flatland optics theory, does indeed coincide with the wavelength lambda as measured by Flatland experiments. Finally, we present an alternative way to understand Flatland optics in the spatial frequency domains of Flatland and Spaceland.