Antitrust and Competition Law Update: Agencies Send a Strong Message on HSR Filing

The Federal Trade Commission and Department of Justice’s Antitrust Division last week each announced enforcement actions against and settlements with parties that alleged failed to make required notifications of transactions under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended. Each case resulted in a significant fine (one of $800,000 and one of$1 million) and signaled the agencies’ intent to pursue vigorously parties that fail -- intentionally or negligently -- to meet their obligations under the HSR Act. Moreover, both cases address the scope of the HSR Act’s “investment only” exemption and show that the agencies construe it strictly to apply only when the acquiror’s interest and intent concerning the acquired firm is truly passive. Finally, these cases serve as a reminder that the Act’s filing requirements apply not only to purchases of an entire company or all of its assets, but also to any purchase of voting securities so long as certain thresholds are met -- whether or not the purchaser obtains any significant percentage ownershi

Short-term-plasticity orchestrates the response of pyramidal cells and interneurons to population bursts

The synaptic drive from neuronal populations varies considerably over short time scales. Such changes in the presynaptic rate trigger many temporal processes absent under steady-state conditions. This paper examines the differential impact of pyramidal cell population bursts on postsynaptic pyramidal cells receiving depressing synapses, and on a class of interneuron that receives facilitating synapses. In experiments a significant shift of the order of of one hundred milliseconds is seen between the response of these two cell classes to the same population burst. It is demonstrated here that such a temporal differentiation of the response can be explained by the synaptic and membranme properties without recourse to elaborate cortical wiring schemes

An informatics model for tissue banks – Lessons learned from the Cooperative Prostate Cancer Tissue Resource

BACKGROUND: Advances in molecular biology and growing requirements from biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Here we describe the CPCTR information management system architecture, common data element (CDE) development, query interfaces, data curation, and quality control. METHODS: Data managers review the medical records to collect and continuously update information for the 145 clinical, pathological and inventorial CDEs that the Resource maintains for each case. An Access-based data entry tool provides de-identification and a standard communication mechanism between each group and a central CPCTR database. Standardized automated quality control audits have been implemented. Centrally, an Oracle database has web interfaces allowing multiple user-types, including the general public, to mine de-identified information from all of the sites with three levels of specificity and granularity as well as to request tissues through a formal letter of intent. RESULTS: Since July 2003, CPCTR has offered over 6,000 cases (38,000 blocks) of highly characterized prostate cancer biospecimens, including several tissue microarrays (TMA). The Resource developed a website with interfaces for the general public as well as researchers and internal members. These user groups have utilized the web-tools for public query of summary data on the cases that were available, to prepare requests, and to receive tissues. As of December 2005, the Resource received over 130 tissue requests, of which 45 have been reviewed, approved and filled. Additionally, the Resource implemented the TMA Data Exchange Specification in its TMA program and created a computer program for calculating PSA recurrence. CONCLUSION: Building a biorepository infrastructure that meets today's research needs involves time and input of many individuals from diverse disciplines. The CPCTR can provide large volumes of carefully annotated prostate tissue for research initiatives such as Specialized Programs of Research Excellence (SPOREs) and for biomarker validation studies and its experience can help development of collaborative, large scale, virtual tissue banks in other organ systems

Calcium Supplementation Increases Blood Creatinine Concentration in a Randomized Controlled Trial

Background: Calcium supplements are widely used among older adults for osteoporosis prevention and treatment. However, their effect on creatinine levels and kidney function has not been well studied. Methods: We investigated the effect of calcium supplementation on blood creatinine concentration in a randomized controlled trial of colorectal adenoma chemoprevention conducted between 2004–2013 at 11 clinical centers in the United States. Healthy participants (N=1,675) aged 45–75 with a history of colorectal adenoma were assigned to daily supplementation with calcium (1200 mg, as carbonate), vitamin D3 (1000 IU), both, or placebo for three or five years. Changes in blood creatinine and total calcium concentration were measured after one year of treatment and multiple linear regression was used to estimate effects on creatinine concentrations. Results: After one year of treatment, blood creatinine was 0.01360.006 mg/dL higher on average among participants randomized to calcium compared to placebo after adjustment for other determinants of creatinine (P = 0.03). However, the effect of calcium treatment appeared to be larger among participants who consumed the most alcohol (2–6 drinks/day) or whose estimated glomerular filtration rate (eGFR) was less than 60 ml/min/1.73 m2 at baseline. The effect of calcium treatment on creatinine was only partially mediated by a concomitant increase in blood total calcium concentration and was independent of randomized vitamin D treatment. There did not appear to be further increases in creatinine after the first year of calcium treatment. Conclusions: Among healthy adults participating in a randomized clinical trial, daily supplementation with 1200 mg of elemental calcium caused a small increase in blood creatinine. If confirmed, this finding may have implications for clinical and public health recommendations for calcium supplementation

Bilingually motivated word segmentation for statistical machine translation

We introduce a bilingually motivated word segmentation approach to languages where word boundaries are not orthographically marked, with application to Phrase-Based Statistical Machine Translation (PB-SMT). Our approach is motivated from the insight that PB-SMT systems can be improved by optimizing the input representation to reduce the predictive power of translation models. We firstly present an approach to optimize the existing segmentation of both source and target languages for PB-SMT and demonstrate the effectiveness of this approach using a Chinese–English MT task, that is, to measure the influence of the segmentation on the performance of PB-SMT systems. We report a 5.44% relative increase in Bleu score and a consistent increase according to other metrics. We then generalize this method for Chinese word segmentation without relying on any segmenters and show that using our segmentation PB-SMT can achieve more consistent state-of-the-art performance across two domains. There are two main advantages of our approach. First of all, it is adapted to the specific translation task at hand by taking the corresponding source (target) language into account. Second, this approach does not rely on manually segmented training data so that it can be automatically adapted for different domains

The CAP cancer protocols – a case study of caCORE based data standards implementation to integrate with the Cancer Biomedical Informatics Grid

BACKGROUND: The Cancer Biomedical Informatics Grid (caBIG™) is a network of individuals and institutions, creating a world wide web of cancer research. An important aspect of this informatics effort is the development of consistent practices for data standards development, using a multi-tier approach that facilitates semantic interoperability of systems. The semantic tiers include (1) information models, (2) common data elements, and (3) controlled terminologies and ontologies. The College of American Pathologists (CAP) cancer protocols and checklists are an important reporting standard in pathology, for which no complete electronic data standard is currently available. METHODS: In this manuscript, we provide a case study of Cancer Common Ontologic Representation Environment (caCORE) data standard implementation of the CAP cancer protocols and checklists model – an existing and complex paper based standard. We illustrate the basic principles, goals and methodology for developing caBIG™ models. RESULTS: Using this example, we describe the process required to develop the model, the technologies and data standards on which the process and models are based, and the results of the modeling effort. We address difficulties we encountered and modifications to caCORE that will address these problems. In addition, we describe four ongoing development projects that will use the emerging CAP data standards to achieve integration of tissue banking and laboratory information systems. CONCLUSION: The CAP cancer checklists can be used as the basis for an electronic data standard in pathology using the caBIG™ semantic modeling methodology

Procjena utjecaja modernizacije i novih tehnoloških procesa na izloženost buci u aluminijskoj industriji

The aim of this study was to assess to which extent modernisation of an aluminium production complex reduced occupational noise hazard for jobs with the highest potential of exposure. Periodical measurements of noise level were taken at the same workplaces using the same method, before and after modernisation of all plants. The results were compared with the recommended standard. After modernisation, the noise was significantly reduced in all sections of all plants. The greatest reduction was measured in the foundry. After modernisation, the portion of workplaces with excessive noise level dropped significantly (chi-square=21.315; p<0.0001) from 78.4 % to 13 %. Noise remained a problem in ingot casting and dross skimming section. In the anode plant, noise remained a problem in the green mill section where noise intensities generated by mills and vibrocompactors varied from 95 dB(A) to 102 dB(A). In the electrolysis plant, the portion of workplaces with extensive noise dropped from 77.8 % to 39.3 % after modernisation (p=0.0019). Noise remains to be a problem at the anode covering section where levels rise up to 100 dB(A). The modernisation of the factory has considerably reduced the noise level in the working environment of all plants, but it can not be reduced completely.Cilj je rada procijeniti utjecaj modernizacije tehnološkog procesa proizvodnje aluminija na prisutnost i razinu buke štetne za zdravlje radnika u radnom okolišu. U tu svrhu uspoređivani su rezultati periodičkih mjerenja razine buke prije i nakon modernizacije. Mjerenja intenziteta buke provedena su na istim radnim mjestima i istom metodom tijekom radnih smjena i uspoređeni s važećim nacionalnim standardom. Nakon modernizacije tvornice u svim odjelima proizvodnih pogona značajno se smanjila razina buke, kao i broj radnih mjesta na kojima su radnici izloženi prekomjernoj buci. Najbolji rezultati postignuti su u ljevaonici, gdje se broj radnih mjesta s prekomjernom razinom buke, tj. razinom buke višom od 90 dB(A) smanjio sa 78.4 % na 13 %. Na radnim mjestima gdje se izlijevaju ingoti i skida šljaka buka je i dalje prekomjerna. U pogonu anoda prekomjerna je buka i dalje prisutna pri proizvodnji sirovih anoda, gdje razina buke zbog rada mlinova i vibrokompresora varira od 95 dB(A) do 102 dB(A). U pogonu elektrolize buka viša od 100 dB(A) izmjerena je pri zasipanju anoda. Iako je modernizacijom tvornice i unaprjeđenjem tehnološkog procesa značajno reducirana razina buke, nije ju moguće u cijelosti ukloniti

The development of common data elements for a multi-institute prostate cancer tissue bank: The Cooperative Prostate Cancer Tissue Resource (CPCTR) experience

BACKGROUND: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a consortium of four geographically dispersed institutions that are funded by the U.S. National Cancer Institute (NCI) to provide clinically annotated prostate cancer tissue samples to researchers. To facilitate this effort, it was critical to arrive at agreed upon common data elements (CDEs) that could be used to collect demographic, pathologic, treatment and clinical outcome data. METHODS: The CPCTR investigators convened a CDE curation subcommittee to develop and implement CDEs for the annotation of collected prostate tissues. The draft CDEs were refined and progressively annotated to make them ISO 11179 compliant. The CDEs were implemented in the CPCTR database and tested using software query tools developed by the investigators. RESULTS: By collaborative consensus the CPCTR CDE subcommittee developed 145 data elements to annotate the tissue samples collected. These included for each case: 1) demographic data, 2) clinical history, 3) pathology specimen level elements to describe the staging, grading and other characteristics of individual surgical pathology cases, 4) tissue block level annotation critical to managing a virtual inventory of cases and facilitating case selection, and 5) clinical outcome data including treatment, recurrence and vital status. These elements have been used successfully to respond to over 60 requests by end-users for tissue, including paraffin blocks from cases with 5 to 10 years of follow up, tissue microarrays (TMAs), as well as frozen tissue collected prospectively for genomic profiling and genetic studies. The CPCTR CDEs have been fully implemented in two major tissue banks and have been shared with dozens of other tissue banking efforts. CONCLUSION: The freely available CDEs developed by the CPCTR are robust, based on "best practices" for tissue resources, and are ISO 11179 compliant. The process for CDE development described in this manuscript provides a framework model for other organ sites and has been used as a model for breast and melanoma tissue banking efforts

Documentation of body mass index and control of associated risk factors in a large primary care network

<p>Abstract</p> <p>Background</p> <p>Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.</p> <p>Methods</p> <p>We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m²), overweight (OW, 25-29.9), and obese (OB, ≥ 30). We measured documentation (yes/no) and control (above/below) of the following three risk factors: blood pressure (BP) ≤130/≤85 mmHg, low-density lipoprotein (LDL) ≤130 mg/dL (3.367 mmol/L), and fasting glucose <100 mg/dL (5.55 mmol/L) or casual glucose <200 mg/dL (11.1 mmol/L).</p> <p>Results</p> <p>BMI was documented in 48,376 patients (61%, range 34-94%), distributed as 30% OB, 34% OW, and 36% NW. Documentation of all three risk factors was higher in obesity (OB = 58%, OW = 54%, NW = 41%, p for trend <0.0001), but control of all three was lower (OB = 44%, OW = 49%, NW = 62%, p = 0.0001). The presence of cardiovascular disease (CVD) or diabetes modified some associations with obesity, and OB patients with CVD or diabetes had low rates of control of all three risk factors (CVD: OB = 49%, OW = 50%, NW = 56%; diabetes: OB = 42%, OW = 47%, NW = 48%, p < 0.0001 for adiposity-CVD or diabetes interaction).</p> <p>Conclusions</p> <p>In a large primary care network BMI documentation has been incomplete and for patients with BMI measured, risk factor control has been poorer in obese patients compared with NW, even in those with obesity and CVD or diabetes. Better knowledge of BMI could provide an opportunity for improved quality in obesity care.</p