Active Region Overheating in Pulsed Quantum Cascade Lasers: Effects of Nonequilibrium Heat Dissipation on Laser Performance.

Mid IR Quantum cascade lasers are of high interest for the scientific community due to their unique applications. However, the QCL designs require careful engineering to overcome some crucial disadvantages. One of them is active region (ARn) overheating, which significantly affects laser characteristics, even in the pulsed mode.

Decentralized clinical trial design using blood microsampling technology for serum bioanalysis.

Alternatives to phlebotomy in clinical trials increase options for patients and clinicians by simplifying and increasing accessibility to clinical trials. The authors investigated the technical and logistical considerations of one technology compared with phlebotomy. Paired samples were collected from 16 donors via a second-generation serum gel microsampling device and conventional phlebotomy.

High-Power Quantum Cascade Lasers Emitting at 8 μm: Technology and Analysis.

In this work, we demonstrate the features of a two-stage epitaxial growth technique and show the results of power and efficiency measurements for three different designs of quantum cascade lasers with a record-high peak power in the 8 μm spectral region. The time-resolved QCL spectral study proves that InP-based upper cladding paired with an InP contact layer provides better heat dissipation and allows one to reach better power characteristics in comparison with InGaAs-based contact, even with short pulse pumping.

Leveraging patient-centric sampling for clinical drug development and decentralized clinical trials: Promise to reality.

Advances in the technologies to enable patient-centric sampling (PCS) have the potential to improve blood sample collection by enabling clinical trial participants to collect samples via self-collection or with the help of a caregiver in their home. Typically, blood samples to assess pharmacokinetics and pharmacodynamics of a drug during clinical development are collected at a clinical site via venous blood draw. In this position paper by the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), the potential value PCS can bring to patients, to the clinical datasets generated, and to clinical trial sponsors is discussed, along with considerations for program decision making, bioanalytical feasibility, operations, and regulatory implications.

Deep forecasting of translational impact in medical research.

The value of biomedical research-a $1.7 trillion annual investment-is ultimately determined by its downstream, real-world impact, whose predictability from simple citation metrics remains unquantified. Here we sought to determine the comparative predictability of future real-world translation-as indexed by inclusion in patents, guidelines, or policy documents-from complex models of title/abstract-level content versus citations and metadata alone.

Comparison of prognostic scales for patients with metastatic spine disease.

This is one-centre retrospective study with the aim to identify the scale, which provides the most accurate prediction of life expectancy in patients with metastatic lesions in spine. A retrospective analysis of clinical data of 138 patients with metastatic spinal tumors. Patients underwent spinal cord decompression and instrumented stabilization of affected area.

[The development of morbidity and mortality encoding in the system of the Ministry of Internal Affairs of Russia].

Despite attempts of improving actual system of morbidity and mortality accounting, the study research established significant real data distortion. These differences do not allow to assess in fullness complete picture of actual morbidity and mortality. Hence, improvement of approaches to increasing efficiency of indices data registration.

Evaluation of a novel blood microsampling device for clinical trial sample collection and protein biomarker analysis.

Evaluation of a novel microsampling device for its use in clinical sample collection and biomarker analysis. Matching samples were collected from 16 healthy donors (ten females, six males; age 42 ± 20) via K2EDTA touch activated phlebotomy (TAP) device and phlebotomy. The protein profile differences between sampling groups was evaluated using aptamer-based proteomic assay SomaScan and selected ELISA.

[The labor standards of osteopath with regard to morbidity coding].

In the article the main planned normative documents on an osteopathy are considered, recommendations about commission of scheduling of number of positions of osteopathic doctors on the basis of the data which are available in statistics on incidence taking into account the available systemic defects of coding on ICD-10 are made.

[Perforated duodenal ulcer in high risk patients].

Aim: To improve the outcomes in patients with perforated duodenal ulcers.

Material And Methods: Cohort study included 456 patients with perforated duodenal ulcer. High risk of mortality was determined in 9% of patients (n=40) considering Boey diagnostic criteria (1982, 1987).

[Prevention of blood loss during resection of hypervascular spinal tumors with the use of preoperative embolization and local hemostatic agents].

Currently there is no consensus how to reduce the risk of hemorrhage in spinal decompression surgery of hypervascu- lar spinal tumors. A retrospective study of 128 patients oper- ated in our institute was held in the period between 2003 and 2014. There were 80 male and 48 female patients with extradural hypervascular spinal tumor.

Electronic processing of informed consents in a global pharmaceutical company environment.

We present an electronic capture tool to process informed consents, which are mandatory recorded when running a clinical trial. This tool aims at the extraction of information expressing the duration of the consent given by the patient to authorize the exploitation of biomarker-related information collected during clinical trials. The system integrates a language detection module (LDM) to route a document into the appropriate information extraction module (IEM).

Large-scale prediction and testing of drug activity on side-effect targets.

Discovering the unintended 'off-targets' that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended 'side-effect' targets.

[Comparative evaluation of marginal adaptation of restorative materials after cavity preparation with different tools in vitro].

In this article the results of laboratory studies that evaluated the marginal adaptation of restorative materials after the preparation of the cavity with different tools in vitro were presented.

Cardiac ion channel safety profiling on the IonWorks Quattro automated patch clamp system.

The normal electrophysiologic behavior of the heart is determined by the integrated activity of specific cardiac ionic currents. Mutations in genes encoding the molecular components of individual cardiac ion currents have been shown to result in multiple cardiac arrhythmia syndromes. Presently, 12 genes associated with inherited long QT syndrome (LQTS) have been identified, and the most common mutations are in the hKCNQ1 (LQT1, Jervell and Lange-Nielson syndrome), hKCNH2 (LQT2), and hSCN5A (LQT3, Brugada syndrome) genes.

[Etiological and prognostic aspects of renal failure in patients with prostatic adenoma].

The aim of our study was to assess the causes of renal failure in patients with prostatic adenoma (PA) and outcomes after draining of the urinary bladder. A retrospective study comprised 239 PA patients with a serum creatinine level over 120 mcmol/l. Outcomes were assessed after 3-5 day and 2.

A lead discovery strategy driven by a comprehensive analysis of proteases in the peptide substrate space.

We present here a comprehensive analysis of proteases in the peptide substrate space and demonstrate its applicability for lead discovery. Aligned octapeptide substrates of 498 proteases taken from the MEROPS peptidase database were used for the in silico analysis. A multiple-category naïve Bayes model, trained on the two-dimensional chemical features of the substrates, was able to classify the substrates of 365 (73%) proteases and elucidate statistically significant chemical features for each of their specific substrate positions.

Plate-based diversity selection based on empirical HTS data to enhance the number of hits and their chemical diversity.

Typically, screening collections of pharmaceutical companies contain more than a million compounds today. However, for certain high-throughput screening (HTS) campaigns, constraints posed by the assay throughput and/or the reagent costs make it impractical to screen the entire deck. Therefore, it is desirable to effectively screen subsets of the collection based on a hypothesis or a diversity selection.

Gaining insight into off-target mediated effects of drug candidates with a comprehensive systems chemical biology analysis.

We present a workflow that leverages data from chemogenomics based target predictions with Systems Biology databases to better understand off-target related toxicities. By analyzing a set of compounds that share a common toxic phenotype and by comparing the pathways they affect with pathways modulated by nontoxic compounds we are able to establish links between pathways and particular adverse effects. We further link these predictive results with literature data in order to explain why a certain pathway is predicted.

Mapping adverse drug reactions in chemical space.

We present a novel method to better investigate adverse drug reactions in chemical space. By integrating data sources about adverse drug reactions of drugs with an established cheminformatics modeling method, we generate a data set that is then visualized with a systems biology tool. Thereby new insights into undesired drug effects are gained.

Use of ligand based models for protein domains to predict novel molecular targets and applications to triage affinity chromatography data.

The elucidation of drug targets is important both to optimize desired compound action and to understand drug side-effects. In this study, we created statistical models which link chemical substructures of ligands to protein domains in a probabilistic manner and employ the model to triage the results of affinity chromatography experiments. By annotating targets with their InterPro domains, general rules of ligand-protein domain associations were derived and successfully employed to predict protein targets outside the scope of the training set.

Which aspects of HTS are empirically correlated with downstream success?

High-throughput screening (HTS) is a well-established hit-finding approach used in the pharmaceutical industry. In this article, recent experience at Novartis with respect to factors influencing the success of HTS campaigns is discussed. An inherent measure of HTS quality could be defined by the assay Z and Z' factors, the number of hits and their biological potencies; however, such measures of quality do not always correlate with the advancement of hits to the later stages of drug discovery.

Chemogenomic data analysis: prediction of small-molecule targets and the advent of biological fingerprint.

Chemogenomics comprises a systematic relationship between targets and ligands that are used as target modulators in living systems such as cells or organisms. In recent years, data on small molecule-bioactivity relationships have become increasingly available, and consequently so have the number of approaches used to translate bioactivity data into knowledge. This review will focus on two aspects of chemogenomics.

[Comparative assessment of resting myocardial perfusion in patients with postinfarct cardiosclerosis by electron-beam tomography and 99mTc-MIBI myocardial single-photon tomography].

The purpose of the study was to compare myocardial perfusion assessed by electron beam computed tomography (EBCT) with that obtained by 99mTc-sestamibi single photon emission computed tomography (SPECT) in patients with old myocardial infarction and control subjects at rest. A total of 42 patients with suspected and known ischaemic heart disease (IHD) were included in the study. 20 pts had a history of Q-wave myocardial infarction (MI), 12 pts had an old non-Q-wave MI and 10 served as controls (without perfusion defects on SPECT images at rest).

Angular variances for internal bond rotations of side chains in GXG-based tripeptides derived from (13)C-NMR relaxation measurements: Implications to protein folding.

The study of backbone and side-chain internal motions in proteins and peptides is crucial to having a better understanding of protein/peptide "structure" and to characterizing unfolded and partially folded states of proteins and peptides. To achieve this, however, requires establishing a baseline for internal motions and motional restrictions for all residues in the fully, solvent-exposed "unfolded state." GXG-based tripeptides are the simpliest peptides where residue X is fully solvent exposed in the context of an actual peptide.