Two examples of non strictly convex large deviations

We present two examples of a large deviations principle where the rate function is not strictly convex. This is motivated by a model used in mathematical finance (the Heston model), and adds a new item to the zoology of non strictly convex large deviations. For one of these examples, we show that the rate function of the Cramer-type of large deviations coincides with that of the Freidlin-Wentzell when contraction principles are applied.Comment: 11 page

An update on MRMAssayDB: a comprehensive resource for targeted proteomics assays in the community

Precise multiplexed quantification of proteins in biological samples can be achieved by targeted proteomics using multiple or parallel reaction monitoring (MRM/PRM). Combined with internal standards, the method achieves very good repeatability and reproducibility enabling excellent protein quantification and allowing longitudinal and cohort studies. A laborious part of performing such experiments lies in the preparation steps dedicated to the development and validation of individual protein assays. Several public repositories host information on targeted proteomics assays, including NCI's Clinical Proteomic Tumor Analysis Consortium assay portals, PeptideAtlas SRM Experiment Library, SRMAtlas, PanoramaWeb, and PeptideTracker, with all offering varying levels of details. We introduced MRMAssayDB in 2018 as an integrated resource for targeted proteomics assays. The Web-based application maps and links the assays from the repositories, includes comprehensive up-to-date protein and sequence annotations, and provides multiple visualization options on the peptide and protein level. We have extended MRMAssayDB with more assays and extensive annotations. Currently it contains >828 000 assays covering >51 000 proteins from 94 organisms, of which >17 000 proteins are present in >2400 biological pathways, and >48 000 mapping to >21 000 Gene Ontology terms. This is an increase of about four times the number of assays since introduction. We have expanded annotations of interaction, biological pathways, and disease associations. A newly added visualization module for coupled molecular structural annotation browsing allows the user to interactively examine peptide sequence and any known PTMs and disease mutations, and map all to available protein 3D structures. Because of its integrative approach, MRMAssayDB enables a holistic view of suitable proteotypic peptides and commonly used transitions in empirical data. Availability: http://mrmassaydb.proteincentre.com.Proteomic

Primer to Voltage Imaging With ANNINE Dyes and Two-Photon Microscopy

ANNINE-6 and ANNINE-6plus are voltage-sensitive dyes that when combined with two-photon microscopy are ideal for recording of neuronal voltages in vivo, in both bulk loaded tissue and the dendrites of single neurons. Here, we describe in detail but for a broad audience the voltage sensing mechanism of fast voltage-sensitive dyes, with a focus on ANNINE dyes, and how voltage imaging can be optimized with one-photon and two-photon excitation. Under optimized imaging conditions the key strengths of ANNINE dyes are their high sensitivity (0.5%/mV), neglectable bleaching and phototoxicity, a linear response to membrane potential, and a temporal resolution which is faster than the optical imaging devices currently used in neurobiology (order of nanoseconds). ANNINE dyes in combination with two-photon microscopy allow depth-resolved voltage imaging in bulk loaded tissue to study average membrane voltage oscillations and sensory responses. Alternatively, if ANNINE-6plus is applied internally, supra and sub threshold voltage changes can be recorded from dendrites of single neurons in awake animals. Interestingly, in our experience ANNINE-6plus labeling is impressively stable in vivo, such that voltage imaging from single Purkinje neuron dendrites can be performed for 2 weeks after a single electroporation of the neuron. Finally, to maximize their potential for neuroscience studies, voltage imaging with ANNINE dyes and two-photon microscopy can be combined with electrophysiological recording, calcium imaging, and/or pharmacology, even in awake animals

Enabling political legitimacy and conceptual integration for climate change adaptation research within an agricultural bureaucracy: a systemic inquiry

The value of using systems approaches, for situations framed as ‘super wicked’, is examined from the perspective of research managers and stakeholders in a state-based climate change adaptation (CCA) program (CliChAP). Polycentric drivers influencing the development of CCA research pre-2010 in Victoria, Australia are reflected on, using Soft Systems Methodology (SSM) to generate a boundary critique of CCA research as a human activity system. We experienced the complexity of purpose with research practices pulling in different directions, reflected on the appropriateness of agricultural bureaucracies’ historical new public management (NPM) practices, and focused on realigning management theory with emerging demands for adaptation research skills and capability. Our analysis conceptualised CliChAP as a subsystem, generating novelty in a wider system, concerned with socio-ecological co-evolution. Constraining/enabling conditions at the time dealing with political legitimacy and conceptual integration were observed as potential catalysts for innovation in research management towards better handling of uncertainty as a social process using systemic thinking in practice (StiP)

Characterization of cytochrome P450 monooxygenase CYP154H1 from the thermophilic soil bacterium Thermobifida fusca

Cytochrome P450 monooxygenases are valuable biocatalysts due to their ability to hydroxylate unactivated carbon atoms using molecular oxygen. We have cloned the gene for a new cytochrome P450 monooxygenase, named CYP154H1, from the moderately thermophilic soil bacterium Thermobifida fusca. The enzyme was overexpressed in Escherichia coli at up to 14% of total soluble protein and purified to homogeneity in three steps. CYP154H1 activity was reconstituted using putidaredoxin reductase and putidaredoxin from Pseudomonas putida DSM 50198 as surrogate electron transfer partners. In biocatalytic reactions with different aliphatic and aromatic substrates of varying size, the enzyme converted small aromatic and arylaliphatic compounds like ethylbenzene, styrene, and indole. Furthermore, CYP154H1 also accepted different arylaliphatic sulfides as substrates chemoselectively forming the corresponding sulfoxides and sulfones. The enzyme is moderately thermostable with an apparent melting temperature of 67°C and exhibited still 90% of initial activity after incubation at 50°C

The role and scope of practice of midwives in humanitarian settings:a systematic review and content analysis

Abstract Background Midwives have an essential role to play in preparing for and providing sexual and reproductive health (SRH) services in humanitarian settings due to their unique knowledge and skills, position as frontline providers and geographic and social proximity to the communities they serve. There are considerable gaps in the international guidance that defines the scope of practice of midwives in crises, particularly for the mitigation and preparedness, and recovery phases. We undertook a systematic review to provide further clarification of this scope of practice and insights to optimise midwifery performance. The review aimed to determine what SRH services midwives are involved in delivering across the emergency management cycle in humanitarian contexts, and how they are working with other professionals to deliver health care. Methods Four electronic databases and the websites of 33 organisations were searched between January and March 2017. Papers were eligible for inclusion if they were published in English between 2007 and 2017 and reported primary research pertaining to the role of midwives in delivering and performing any component of sexual and/or reproductive health in humanitarian settings. Content analysis was used to map the study findings to the Minimum Initial Service Package (MISP) for SRH across the three phases of the disaster management cycle and identify how midwives work with other members of the health care team. Results Fourteen studies from ten countries were included. Twelve studies were undertaken in conflict settings, and two were conducted in the context of the aftermath of natural disasters. We found a paucity of evidence from the research literature that examines the activities and roles undertaken by midwives across the disaster management cycle. This lack of evidence was more apparent during the mitigation and preparedness, and recovery phases than the response phase of the disaster management cycle. Conclusion Research-informed guidelines and strategies are required to better align the scope of practice of midwives with the objectives of multi-agency guidelines and agreements, as well as the activities of the MISP, to ensure that the potential of midwives can be acknowledged and optimised across the disaster management cycle

State of newborn care in South Sudan’s displacement camps: a descriptive study of facility-based deliveries

BACKGROUND: Approximately 2.7 million neonatal deaths occur annually, with highest rates of neonatal mortality in countries that have recently experienced conflict. Constant instability in South Sudan further strains a weakened health system and poses public health challenges during the neonatal period. We aimed to describe the state of newborn facility-level care in displaced person camps across Juba, Malakal, and Maban. METHODS: We conducted clinical observations of the labor and delivery period, exit interviews with recently delivered mothers, health facility assessments, and direct observations of midwife time-use. Study participants were mother-newborn pairs who sought services and birth attendants who provided delivery services between April and June 2016 in five health facilities. RESULTS: Facilities were found to be lacking the recommended medical supplies for essential newborn care. Two of the five facilities had skilled midwives working during all operating hours, with 6.2% of their time spent on postnatal care. Selected components of thermal care (62.5%), infection prevention (74.8%), and feeding support (63.6%) were commonly practiced, but postnatal monitoring (27.7%) was less consistently observed. Differences were found when comparing the primary care level to the hospital (thermal: relative risk [RR] 0.48 [95% CI] 0.40–0.58; infection: RR 1.28 [1.11–1.47]; feeding: RR 0.49 [0.40–0.58]; postnatal: RR 3.17 [2.01–5.00]). In the primary care level, relative to newborns delivered by traditional birth attendants, those delivered by skilled attendants were more likely to receive postnatal monitoring (RR 1.59 [1.09-2. 32]), but other practices were not statistically different. Mothers’ knowledge of danger signs was poor, with fever as the highest reported (44.8%) followed by not feeding well (41.0%), difficulty breathing (28.9%), reduced activity (27.7%), feeling cold (18.0%) and convulsions (11.2%). CONCLUSIONS: Addressing health service delivery in contexts affected by conflict is vital to reducing the global newborn mortality rate and reaching the Sustainable Development Goals. Gaps in intrapartum and postnatal care, particularly skilled care at birth, suggest a critical need to build the capacity of the existing health workforce while increasing access to skilled deliveries.IS

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)