Automated Library Generation and Serendipity Quantification Enables Diverse Discovery in Coordination Chemistry.

Library generation experiments are a key part of the discovery of new materials, methods, and models in chemistry, but the question of how to generate high quality libraries to enable discovery is nontrivial. Herein, we use coordination chemistry to demonstrate the automation of many of the workflows used for library generation in automated hardware including the Chemputer. First, we explore the target-oriented synthesis of three influential coordination complexes, to validate key synthetic operations in our system; second, the generation of focused libraries in chemical and process space; and third, the development of a new workflow for prospecting library formation. This involved Bayesian optimization using a Gaussian process as surrogate model combined with a metric for novelty (or serendipity) quantification based on mass spectrometry data. In this way, we show directed exploration of a process space toward those areas with rarer observations and build a picture of the diversity in product distributions present across the space. We show that this effectively "engineers" serendipity into our search through the unexpected appearance of acetic anhydride, formed in situ, and solvent degradation products as ligands in an isolable series of three Co(III) anhydride complexes.

An Autonomous Chemical Robot Discovers the Rules of Inorganic Coordination Chemistry without Prior Knowledge.

We present a chemical discovery robot for the efficient and reliable discovery of supramolecular architectures through the exploration of a huge reaction space exceeding ten billion combinations. The system was designed to search for areas of reactivity found through autonomous selection of the reagent types, amounts, and reaction conditions aiming for combinations that are reactive. The process consists of two parts where reagents are mixed together, choosing from one type of aldehyde, one amine and one azide (from a possible family of two amines, two aldehydes and four azides) with different volumes, ratios, reaction times, and temperatures, whereby the reagents are passed through a copper coil reactor. Next, either cobalt or iron is added, again from a large number of possible quantities. The reactivity was determined by evaluating differences in pH, UV-Vis, and mass spectra before and after the search was started. The algorithm was focused on the exploration of interesting regions, as defined by the outputs from the sensors, and this led to the discovery of a range of 1-benzyl-(1,2,3-triazol-4-yl)-N-alkyl-(2-pyridinemethanimine) ligands and new complexes: [Fe(L1 )2 ](ClO4 )2 (1); [Fe(L2 )2 ](ClO4 )2 (2); [Co2 (L3 )2 ](ClO4 )4 (3); [Fe2 (L3 )2 ](ClO4 )4 (4), which were crystallised and their structure confirmed by single-crystal X-ray diffraction determination, as well as a range of new supramolecular clusters discovered in solution using high-resolution mass spectrometry.

A cross-source, system-agnostic solution for clinical data review.

Assembly of complete and error-free clinical trial data sets for statistical analysis and regulatory submission requires extensive effort and communication among investigational sites, central laboratories, pharmaceutical sponsors, contract research organizations and other entities. Traditionally, this data is captured, cleaned and reconciled through multiple disjointed systems and processes, which is resource intensive and error prone. Here, we introduce a new system for clinical data review that helps data managers identify missing, erroneous and inconsistent data and manage queries in a unified, system-agnostic and efficient way. Our solution enables timely and integrated access to all study data regardless of source, facilitates the review of validation and discrepancy checks and the management of the resulting queries, tracks the status of page review, verification and locking activities, monitors subject data cleanliness and readiness for database lock and provides extensive configuration options to meet any study's needs, automation for regular updates and fit-for-purpose user interfaces for global oversight and problem detection.

Femoral insufficiency fractures with bisphosphonate therapy. Cases study.

The aim of this paper is to analyze on clinical cases specific features of femoral insufficiency fractures during bisphosphonates therapy. We are presenting two insufficiency femoral fractures (2 patients) in patients receiving bisphosphonate therapy. These two cases represent new type of femoral fractures. These are low energy or spontaneous fractures of diaphysis and subtrochanteric region. Prodromal pain is often observed. On x-rays thick lateral cortex, its ellipsoid thickening and transverse or oblique fracture line is observed. Many authors link such fractures to long-term bisphosphonate therapy. Patients on long term bisphosphonate therapy present with new and specific fracture pattern of femoral bone. Fractures of this pattern are extremely rare. The risk benefit ratio of bisphosphonates therapy is not changed.

[Effect of intramedullary nailing of tibial shaft fractures on the pressure in the deep posterior compartment of the leg]. / Wplyw zespolenia zlamania kosci piszczelowej gwozdziem sródszpikowym na cisnienie sródtkankowe w przedziale tylnym glebokim goleni.

In the years of 2003-2005 there was carried out an investigation on 24 patients (17 male and 7 female) based on measuring the pressure in the deep posterior compartment during tibial intramedullary nailing with reaming. The pressure was checked in each part of the operation. The mean increase of the pressure was 7% (+ 1.6 mmHg) and didn't cause any risk of compartment syndrome. In our opinion the intramedullary nailing might be consider as a safe procedure.

[Removal of broken interlocking nails and reosteosynthesis--related clinical problems]. / Problem usuwania i reosteosyntezy po zlamaniu ryglowanych gwozdzi sródszpikowych.

Nine patients with six fractures of the intramedullary cannulated nails and four Gamma nails are presented. In five patients broken implants had been removed by simple and safe method by use of tape extractor and than four patients has had intramedullary reosteosynthesis by closed method. The main causes in most cases were technical errors and early full weighbearing.