A proteomic approach for the rapid, multi-informative and reliable identification of blood

Blood evidence is frequently encountered at the scene of violent crimes and can provide valuable intelligence in the forensic investigation of serious offences. Because many of the current enhancement methods used by crime scene investigators are presumptive, the visualisation of blood is not always reliable nor does it bear additional information. In the work presented here, two methods employing a shotgun bottom up proteomic approach for the detection of blood are reported; the developed protocols employ both an in solution digestion method and a recently proposed procedure involving immobilization of trypsin on hydrophobin Vmh2 coated MALDI sample plate. The methods are complementary as whilst one yields more identifiable proteins (as biomolecular signatures), the other is extremely rapid (5 minutes). Additionally, data demonstrate the opportunity to discriminate blood provenance even when two different blood sources are present in a mixture. This approach is also suitable for old bloodstains which had been previously chemically enhanced, as experiments conducted on a 9-year-old bloodstain deposited on a ceramic tile demonstrate

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial.

Purpose Hydrogen peroxide (H2O2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H2O2 + external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action.Methods and materials Twelve patients with breast tumors ≥3 cm (surgically or medically inoperable) received intratumoral H2O2 with either 36 Gy in 6 twice-weekly fractions (n = 6) or 49.5 Gy in 18 daily fractions (n = 6) to the whole breast ± locoregional lymph nodes in a single-center, nonrandomized study. H2O2 was mixed in 1% sodium hyaluronate gel (final H2O2 concentration 0.5%) before administration to slow drug release and minimize local discomfort. The mixture was injected intratumorally under ultrasound guidance twice weekly 1 hour before RT. The primary endpoint was patient-reported maximum intratumoral pain intensity before and 24 hours postinjection. Secondary endpoints included grade ≥3 skin toxicity and tumor response by ultrasound. Blood samples were collected before, during, and at the end of treatment for cell-death and immune marker analysis.Results Compliance with H2O2 and RT was 100%. Five of 12 patients reported moderate pain after injection (grade 2 Common Terminology Criteria for Adverse Events v4.02) with median duration 60 minutes (interquartile range, 20-120 minutes). Skin toxicity was comparable to RT alone, with maintained partial/complete tumor response relative to baseline in 11 of 12 patients at last follow-up (median 12 months). Blood marker analysis highlighted significant associations of TRAIL, IL-1β, IL-4, and MIP-1α with tumor response.Conclusions Intratumoral H2O2 with RT is well tolerated with no additional toxicity compared with RT alone. If efficacy is confirmed in a randomized phase 2 trial, the approach has potential as a cost-effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor

The highly rearranged mitochondrial genomes of the crabs Maja crispata and Maja squinado (Majidae) and gene order evolution in Brachyura

Abstract We sequenced the mitochondrial genomes of the spider crabs Maja crispata and Maja squinado (Majidae, Brachyura). Both genomes contain the whole set of 37 genes characteristic of Bilaterian genomes, encoded on both \u3b1- and \u3b2-strands. Both species exhibit the same gene order, which is unique among known animal genomes. In particular, all the genes located on the \u3b2-strand form a single block. This gene order was analysed together with the other nine gene orders known for the Brachyura. Our study confirms that the most widespread gene order (BraGO) represents the plesiomorphic condition for Brachyura and was established at the onset of this clade. All other gene orders are the result of transformational pathways originating from BraGO. The different gene orders exhibit variable levels of genes rearrangements, which involve only tRNAs or all types of genes. Local homoplastic arrangements were identified, while complete gene orders remain unique and represent signatures that can have a diagnostic value. Brachyura appear to be a hot-spot of gene order diversity within the phylum Arthropoda. Our analysis, allowed to track, for the first time, the fully evolutionary pathways producing the Brachyuran gene orders. This goal was achieved by coupling sophisticated bioinformatic tools with phylogenetic analysis

Process Mining Routinely Collected Electronic Health Records to Define Real-Life Clinical Pathways during Chemotherapy

Background: There is growing interest in the use of routinely collected electronic health records to enhance service delivery and facilitate clinical research. It should be possible to detect and measure patterns of care and use the data to monitor improvements but there are methodological and data quality challenges. Driven by the desire to model the impact of a patient self-test blood count monitoring service in patients on chemotherapy, we aimed to (i) establish reproducible methods of process-mining electronic health records, (ii) use the outputs derived to define and quantify patient pathways during chemotherapy, and (iii) to gather robust data which is structured to be able to inform a cost-effectiveness decision model of home monitoring of neutropenic status during chemotherapy. Methods: Electronic Health Records at a UK oncology centre were included if they had (i) a diagnosis of metastatic breast cancer and received adjuvant epirubicin and cyclosphosphamide chemotherapy or (ii) colorectal cancer and received palliative oxaliplatin and infusional 5-fluorouracil chemotherapy, and (iii) were first diagnosed with cancer between January 2004 and February 2013. Software and a Markov model were developed, producing a schematic of patient pathways during chemotherapy. Results: Significant variance from the assumed care pathway was evident from the data. Of the 535 patients with breast cancer and 420 with colorectal cancer there were 474 and 329 pathway variants respectively. Only 27 (5%) and 26 (6%) completed the planned six cycles of chemotherapy without having unplanned hospital contact. Over the six cycles, 169 (31.6%) patients with breast cancer and 190 (45.2%) patients with colorectal cancer were admitted to hospital. Conclusion: The pathways of patients on chemotherapy are complex. An iterative approach to addressing semantic and data quality issues enabled the effective use of routinely collected patient records to produce accurate models of the real-life experiences of chemotherapy patients and generate clinically useful information. Very few patients experience the idealised patient pathway that is used to plan their care. A better understanding of real-life clinical pathways through process mining can contribute to care and data quality assurance, identifying unmet needs, facilitating quantification of innovation impact, communicating with stakeholders, and ultimately improving patient care and outcomes

Selection Mechanisms Underlying High Impact Biomedical Research - A Qualitative Analysis and Causal Model

BACKGROUND: Although scientific innovation has been a long-standing topic of interest for historians, philosophers and cognitive scientists, few studies in biomedical research have examined from researchers' perspectives how high impact publications are developed and why they are consistently produced by a small group of researchers. Our objective was therefore to interview a group of researchers with a track record of high impact publications to explore what mechanism they believe contribute to the generation of high impact publications. METHODOLOGY/PRINCIPAL FINDINGS: Researchers were located in universities all over the globe and interviews were conducted by phone. All interviews were transcribed using standard qualitative methods. A Grounded Theory approach was used to code each transcript, later aggregating concept and categories into overarching explanation model. The model was then translated into a System Dynamics mathematical model to represent its structure and behavior. Five emerging themes were found in our study. First, researchers used heuristics or rules of thumb that came naturally to them. Second, these heuristics were reinforced by positive feedback from their peers and mentors. Third, good communication skills allowed researchers to provide feedback to their peers, thus closing a positive feedback loop. Fourth, researchers exhibited a number of psychological attributes such as curiosity or open-mindedness that constantly motivated them, even when faced with discouraging situations. Fifth, the system is dominated by randomness and serendipity and is far from a linear and predictable environment. Some researchers, however, took advantage of this randomness by incorporating mechanisms that would allow them to benefit from random findings. The aggregation of these themes into a policy model represented the overall expected behavior of publications and their impact achieved by high impact researchers. CONCLUSIONS: The proposed selection mechanism provides insights that can be translated into research coaching programs as well as research policy models to optimize the introduction of high impact research at a broad scale among institutional and governmental agencies

Worm control practice against gastro-intestinal parasites in Norwegian sheep and goat flocks

<p>Abstract</p> <p>Background</p> <p>Anthelmintic treatment is the most common way of controlling nematode infections in ruminants. However, several countries have reported anthelmintic resistance (AR), representing a limitation for sustainable small ruminant production. The knowledge regarding worm control management represents a baseline to develop a guideline for preventing AR. The aim of the present study was therefore to improve our knowledge about the worm control practices in small ruminant flocks in Norway.</p> <p>Methods</p> <p>A questionnaire survey regarding worm control practices was performed in small ruminant flocks in Norway. Flocks were selected from the three main areas of small ruminant farming, i.e. the coastal, inland and northern areas. A total of 825 questionnaires, comprising 587 sheep flocks (return rate of 51.3%) and 238 goat flocks (52.6%) were included.</p> <p>Results</p> <p>The results indicated that visual appraisal of individual weight was the most common means of estimating the anthelmintic dose used in sheep (78.6%) and goat (85.1%) flocks. The mean yearly drenching rate in lambs and ewes were 2.5 ± 1.7 and 1.9 ± 1.1, respectively, whereas it was 1.0 (once a year) in goats. However, these figures were higher in sheep in the coastal area with a rate of 3.4 and 2.2 in lambs and ewes, respectively. Benzimidazoles were the predominant anthelmintic class used in sheep flocks (64.9% in 2007), whereas benzimidazoles and macrocyclic lactones were both equally used in dairy goat flocks. In the period of 2005-2007, 46.3% of the sheep flocks never changed the anthelmintic class. The dose and move strategy was practiced in 33.2% of the sheep flocks.</p> <p>Conclusions</p> <p>The present study showed that inaccurate weight calculation gives a risk of under-dosing in over 90% of the sheep and goat flocks in Norway. Taken together with a high treatment frequency in lambs, a lack of anthelmintic class rotation and the common use of a dose-and-move strategy, a real danger for development of anthelmintic resistance (AR) seems to exist in Norwegian sheep and goat flocks. This risk seems particularly high in coastal areas where high treatment frequencies in lambs were recorded.</p

Using system dynamics for collaborative design: a case study

<p>Abstract</p> <p>Background</p> <p>In order to facilitate the collaborative design, system dynamics (SD) with a group modelling approach was used in the early stages of planning a new stroke unit. During six workshops a SD model was created in a multiprofessional group.</p> <p>Aim</p> <p>To explore to which extent and how the use of system dynamics contributed to the collaborative design process.</p> <p>Method</p> <p>A case study was conducted using several data sources.</p> <p>Results</p> <p>SD supported a collaborative design, by facilitating an explicit description of stroke care process, a dialogue and a joint understanding. The construction of the model obliged the group to conceptualise the stroke care and experimentation with the model gave the opportunity to reflect on care.</p> <p>Conclusion</p> <p>SD facilitated the collaborative design process and should be integrated in the early stages of the design process as a quality improvement tool.</p

Ivermectin, ‘Wonder drug’ from Japan: the human use perspective

Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil—has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Originally introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock and companion animals. It was quickly discovered to be ideal in combating two of the world’s most devastating and disfiguring diseases which have plagued the world’s poor throughout the tropics for centuries. It is now being used free-of-charge as the sole tool in campaigns to eliminate both diseases globally. It has also been used to successfully overcome several other human diseases and new uses for it are continually being found. This paper looks in depth at the events surrounding ivermectin’s passage from being a huge success in Animal Health into its widespread use in humans, a development which has led many to describe it as a “wonder” drug