Defining the molecular pathology of pancreatic body and tail adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease, with very little improvement in survival over the past 50 years. Recent large-scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas. METHODS: Detailed correlative analysis of clinicopathological variables, including tumour location, genomic and transcriptomic data, was performed using the Australian Pancreatic Cancer Genome Initiative (APGI) cohort, part of the International Cancer Genome Consortium study. RESULTS: Clinicopathological data were available for 518 patients recruited to the APGI, of whom 421 underwent genomic analyses; 179 of these patients underwent whole-genome and 96 RNA sequencing. Patients with tumours of the body and tail had significantly worse survival than those with pancreatic head tumours (12·1 versus 22·0 months; P = 0·001). Location in the body and tail was associated with the squamous subtype of PDAC. Body and tail PDACs enriched for gene programmes involved in tumour invasion and epithelial-to-mesenchymal transition, as well as features of poor antitumour immune response. Whether this is due to a molecular predisposition from the outset, or reflects a later time point on the tumour molecular clock, requires further investigation using well designed prospective studies in pancreatic cancer. CONCLUSION: PDACs of the body and tail demonstrate aggressive tumour biology that may explain worse clinical outcomes.

Assisted vaginal delivery in low and middle income countries: an overview.

OBJECTIVE: To assess the use of assisted vaginal delivery (AVD) in low- and middle-income countries (LMICs), highlighting what level of care procedures were performed and identifying systemic barriers to its use. DESIGN: Cross-sectional health facility assessments. SETTING: Up to 40 countries in Latin America, sub-Saharan Africa and Asia. POPULATION: Assessments tended to be national in scope and included all hospitals and samples of midlevel facilities in public and private sectors. METHODS: Descriptive secondary data analysis. MAIN OUTCOME MEASURES: Percentage of facilities where health workers performed AVD in the 3 months prior to the assessment, instrument preference, which health workers performed the procedure, and reasons AVD was not practiced. RESULTS: Fewer than 20% of facilities in Latin America reported performing AVD in the last 3 months. In sub-Saharan Africa, 53% of 1728 hospitals had performed AVD but only 6% of nearly 10 000 health centres had done so. It was not uncommon to find <1% of institutional births delivered by AVD. Vacuum extraction appears preferred over forceps. Lack of equipment and trained health workers were the most frequent reasons for non-performance. CONCLUSIONS: The low use of AVD in LMICs is in contrast with many high-income countries, where high caesarean rates are also associated with significant rates of AVD. In many LMICs, rising caesarean rates have not been associated with maintenance of skills and practice of AVD. AVD is underused precisely in countries where pregnant women continue to face hardships accessing emergency obstetric care and where caesarean delivery can be relatively unsafe. TWEETABLE ABSTRACT: Many LMICs exhibit low use of assisted vaginal delivery where access to EmONC continues to be a hardship.

Relationships between water and paddlefish Polyodon spathula dentary elemental and stable-isotopic signatures: potential application for reconstructing environmental history.

The objectives of this study were to characterize relationships between water and paddlefish Polyodon spathula dentary Sr:Ca, δ18 O and stable hydrogen isotope ratio (δD) to determine the accuracy with which individual P. spathula could be assigned to their collection locations using dentary-edge Sr:Ca, δD and δ18 O. A laboratory experiment was also conducted to determine whether dentary Sr:Ca in age 0 year P. spathula would reflect shifts in water Sr:Ca to which fish were exposed. Significant linear relationships between water and dentary Sr:Ca, δD and δ18 O were observed, although the relationship between water and dentary δ18 O was weaker than those for Sr:Ca and δD. Classification success for individual fish to collection locations that differed in water Sr:Ca, δD and δ18 O ranged from 86 to 100% based on dentary-edge Sr:Ca, δD and δ18 O. Dentary Sr:Ca increased significantly in laboratory-reared age 0 year P. spathula following 4 weeks of exposure to elevated water Sr:Ca; dentary Sr:Ca of fish held in water with elevated Sr:Ca was also significantly higher than that of control fish reared in ambient laboratory water. Results indicated that P. spathula dentaries reflect water signatures for commonly-applied natural chemical markers and strongly suggest that dentary microchemistry and stable-isotopic compositions will be applicable for reconstructing P. spathula environmental history in locations where sufficient spatial differences in water chemistry occur.

Validation of sleep nasendoscopy for assessment of snoring with bispectral index monitoring.

Bispectral index (BIS) monitor is a neurophysiological monitoring device which continually analyses a patient's electroencephalogram during sedation and general anaesthesia to assess the level of consciousness and depth of anaesthesia. BIS monitoring, whilst performing sleep nasendoscopy (using midazolam and propofol), has helped validate depth of sedation and allowed comparison with levels of sedation of control patients during natural sleep. A prospective study of 30 patients with snoring undergoing sleep nasendoscopy with BIS monitoring was conducted. BIS monitoring was recorded throughout the procedure and assessment of snoring was made at the appropriate level of sedation and snoring. BIS values were compared with control patients. The 30 patients undergoing sleep nasendoscopy had average BIS values ranging from 50.72 to 61.2. Similar results were seen with BIS and oxygen saturation in the control group. BIS monitoring provides an adjunct to the assessment of sleep nasendoscopy in determining the level of sedation required for snoring assessment. Comparable BIS values and oxygen saturation levels were obtained between controls and patients during sedation-induced sleep, thus validating the role of sleep nasendoscopy.

Strategic placement of automated external defibrillators (AEDs) for cardiac arrests in public locations and private residences.

Aim: The aim of our study was to determine whether businesses can be identified that rank highly for their potential to improve coverage of out-of-hospital cardiac arrests (OHCAs) by automated external defibrillators (AEDs), both in public locations and private residences. Methods: The cohort comprised 10,422 non-traumatic OHCAs from 2014 to 2020 in Perth, Western Australia. We ranked 115 business brands (across 5,006 facilities) for their potential to supplement coverage by the 3,068 registered public-access AEDs in Perth, while accounting for AED access hours. Results: Registered public-access AEDs provided 100 m coverage of 23% of public-location arrests, and 4% of arrests in private residences. Of the 10 business brands ranked highest for increasing the coverage of public OHCAs, six brands were ranked in the top 10 for increased coverage of OHCAs in private residences. A public phone brand stood out clearly as the highest-ranked of all brands, with more than double the coverage-increase of the second-ranked brand. If all 115 business brands hosted AEDs with 24-7 access, 57% of OHCAs would remain without 100 m coverage for public arrests, and 92% without 100 m coverage for arrests in private residences. Conclusion: Many businesses that ranked highly for increased coverage of arrests in public locations also rank well for increasing coverage of arrests in private residences. However, even if the business landscape was highly saturated with AEDs, large gaps in coverage of OHCAs would remain, highlighting the importance of considering other modes of AED delivery in metropolitan landscapes.

V2O3(0001) surface termination: phase equilibrium.

Complementary but independent medium-energy and low-energy ion scattering studies of the (0001) surfaces of V(2)O(3) films grown on Pd(111), Au(111) and Cu(3)Au(100) reveal a reconstructed full O(3)-layer termination creating a VO(2) surface trilayer. This structure is fully consistent with previous calculations based on thermodynamic equilibrium at the surface during growth, but contrasts with previous suggestions that the surface termination comprises a complete monolayer of vanadyl (V=O) species.

The origin of skeletal muscle stem cells in the embryo and the adult.

Skeletal muscle progenitors are specified during embryogenesis and in addition have recently been found to be generated from either mesenchymal or neural stem cells in the adult. We review recent progress in identifying the signals and transcription factors that control skeletal muscle formation during embryogenesis and in the adult.

Synthesis of a new element with atomic number Z = 117.

The discovery of a new chemical element with atomic number Z=117 is reported. The isotopes (293)117 and (294)117 were produced in fusion reactions between (48)Ca and (249)Bk. Decay chains involving 11 new nuclei were identified by means of the Dubna gas-filled recoil separator. The measured decay properties show a strong rise of stability for heavier isotopes with Z > or = 111, validating the concept of the long sought island of enhanced stability for superheavy nuclei.

Supporting primary health care nurse practitioners' transition to practice.

OBJECTIVE: To examine role transition and support requirements for nurse practitioner (NP) graduates in their first year of practice from the perspectives of the NPs and coparticipants familiar with the NPs' practices; and to make recommendations for practice, education, and policy. DESIGN: Descriptive qualitative design informed by focused ethnography and narrative analysis using semistructured, in-depth, qualitative interviews. SETTING: Primary health care (PHC) settings in Ontario in which NPs worked. PARTICIPANTS: Twenty-three NPs who had graduated from the Ontario Primary Health Care Nurse Practitioner program, and 21 coparticipants including family physicians, NPs, and managers who were familiar with the NPs' practices. METHODS: Anglophone and francophone NPs in their first year of practice in PHC settings were contacted by e-mail or letter. Participating NPs nominated colleagues in the workplace who could comment on their practice. Interviews were conducted within the first 3 months, at 6 months, and at 12 months of the NPs' first year of practice and were transcribed verbatim and coded. Job descriptions and organizational charts demonstrating the NPs' organization positions were also analyzed. The researchers collaboratively analyzed the interviews using a systematic data analysis protocol. MAIN FINDINGS: Familiarity of colleagues and employers with the NP role and scope of practice was an important element in successful NP role transition. Lack of preparation for integrating NPs into clinical settings and lack of infrastructure, orientation, mentorship, and awareness of the NP role and needs made the transition difficult for many. One-third of the NPs had changed employment, identifying interprofessional conflict or problems with acceptance of their role in new practice environments as reasons for the change. CONCLUSION: The transition of NP graduates in Ontario was complicated by the health care environment being ill-prepared to receive them owing to rapid changes in PHC. Strategies for mentorship and for the integration of new NPs into PHC settings are available and need to be implemented by health professionals and administrators. Recommendations for family physicians to support NP graduate transition into practice are provided.

Location and Setting of the Mars InSight Lander, Instruments, and Landing Site.

Knowing precisely where a spacecraft lands on Mars is important for understanding the regional and local context, setting, and the offset between the inertial and cartographic frames. For the InSight spacecraft, the payload of geophysical and environmental sensors also particularly benefits from knowing exactly where the instruments are located. A ~30 cm/pixel image acquired from orbit after landing clearly resolves the lander and the large circular solar panels. This image was carefully georeferenced to a hierarchically generated and coregistered set of decreasing resolution orthoimages and digital elevation models to the established positive east, planetocentric coordinate system. The lander is located at 4.502384°N, 135.623447°E at an elevation of -2,613.426 m with respect to the geoid in Elysium Planitia. Instrument locations (and the magnetometer orientation) are derived by transforming from Instrument Deployment Arm, spacecraft mechanical, and site frames into the cartographic frame. A viewshed created from 1.5 m above the lander and the high-resolution orbital digital elevation model shows the lander is on a shallow regional slope down to the east that reveals crater rims on the east horizon ~400 m and 2.4 km away. A slope up to the north limits the horizon to about 50 m away where three rocks and an eolian bedform are visible on the rim of a degraded crater rim. Azimuths to rocks and craters identified in both surface panoramas and high-resolution orbital images reveal that north in the site frame and the cartographic frame are the same (within 1°).

Sounding the stratosphere and mesosphere by infrared limb scanning from space.

Inversion of the measurements obtained by the infrared limb scanner on the Nimbus 6 satellite has demonstrated that the stratospheric and mesospheric temperatures and ozone concentrations may be obtained remotely from space with accuracy and precision comparable to in situ methods. Such global data have many applications in middle atmospheric research and operational temperature sounding.

ADAM12 is a circulating marker for stromal activation in pancreatic cancer and predicts response to chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma that harbors tumor-promoting properties. No good biomarkers exist to monitor the effect of stromal targeting therapies or to predict response. We set out to identify such non-invasive markers for PDAC stroma and predict response to therapy. Gene expression datasets, co-culture experiments, xenografts, and patient samples were analyzed. Serum samples were measured from a cohort of 58 resected patients, and 87 metastatic or locally advanced PDAC patients. Baseline and follow-up levels were assessed in 372 additional metastatic PDAC patients who received nab-paclitaxel with gemcitabine (n = 184) or gemcitabine monotherapy (n = 188) in the phase III MPACT trial. Increased levels of ADAM12 were found in PDAC patients compared to healthy controls (p < 0.0001, n = 157 and n = 38). High levels of ADAM12 significantly associated with poor outcome in resected PDAC (HR 2.07, p = 0.04). In the MPACT trial survival was significantly longer for patients who received nab-paclitaxel and had undetectable ADAM12 levels before treatment (OS 12.3 m vs 7.9 m p = 0.0046). Consistently undetectable or decreased ADAM12 levels during treatment significantly associated with longer survival as well (OS 14.4 m and 11.2 m, respectively vs 8.3, p = 0.0054). We conclude that ADAM12 is a blood-borne proxy for stromal activation, the levels of which have prognostic significance and correlate with treatment benefit.

The CDK7-cycH-p36 complex of transcription factor IIH phosphorylates p53, enhancing its sequence-specific DNA binding activity in vitro.

Phosphorylation is believed to be one of the mechanisms by which p53 becomes activated or stabilized in response to cellular stress. Previously, p53 was shown to interact with three components of transcription factor IIH (TFIIH): excision repair cross-complementing types 2 and 3 (ERCC2 and ERCC3) and p62. This communication demonstrates that p53 is phosphorylated by the TFIIH-associated kinase in vitro. The phosphorylation was found to be catalyzed by the highly purified kinase components of TFIIH, the CDK7-cycH-p36 trimeric complex. The phosphorylation sites were mapped to the C-terminal amino acids located between residues 311 and 393. Serines 371, 376, 378, and 392 may be the potential sites for this kinase. Phosphorylation of p53 by this kinase complex enhanced the ability of p53 to bind to the sequence-specific p53-responsive DNA element as shown by gel mobility shift assays. These results suggest that the CDK7-cycH-p36 trimeric complex of TFIIH may play a role in regulating p53 functions in cells.

Field notes and theoretical memos in grounded theory.

In this article the authors expose some of the mystique surrounding field notes and theoretical memos in a Glaserian grounded theory study. Definitions, types, and content of field notes and theoretical memos are presented. Exemplars from a study of mothers living with serious mental illness are provided to illustrate how these forms of documentation evolved during the course of the study. The authors argue that, although the processes of field noting and memoing may blur as a study progresses, they nevertheless retain their independent functions. The authors contend that without understanding the complementary function of these two types of documentation, data cannot evolve to a higher interpretive level. This article contributes specific ideas for improving the methods used by qualitative nurse researchers.

Modeling Sexual Assault Risk Perception Among Heterosexual College Females: The Impact of Previous Victimization, Alcohol Use, and Coping Style.

This investigation utilizes structural equation modeling (SEM) to build and test a comprehensive model of specific and global risk perception. A sample of 325 undergraduate females responded to measures of previous victimization, problematic alcohol use, and maladaptive coping. They also rated perceived risk in multiple hypothetical dating vignettes. The results revealed strong relationships between problematic alcohol use and both decreased specific and increased global risk perception. In addition, previous victimization and maladaptive coping were related to increased global risk perception and specific risk perception, respectively. These findings carry implications for theories of risk perception and point to new approaches for research.

The effects of gold and Co-adsorbed carbon on the adsorption and thermal decomposition of acetic acid on Pd{111}.

The growth and annealing behavior of ultrathin Au films on Pd{111} were monitored with scanning tunneling microscopy (STM) and medium energy ion scattering (MEIS). The adsorption of acetic acid on both clean and deliberately carbon-contaminated bimetallic surfaces was investigated with reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD). We report that the surface chemistry of acetic acid is strongly modified by the presence of Au in the bimetallic surface which acts both to stabilize adsorbed acetate and to decrease the tendency of acetic acid to decompose on adsorption to produce adsorbed carbon. The adsorption of acetic acid at 300 K is found to cause measurable segregation of Pd to the surface for all surface compositions tested.

The United Nations Process Indicators for emergency obstetric care: Reflections based on a decade of experience.

OBJECTIVE: The paper reviews the experience with the EmOC process indicators, and evaluates whether the indicators serve the purposes for which they were originally created - to gather and interpret relatively accessible data to design and implement EmOC service programs. METHOD: We review experience with each of the 6 process indicators individually, and monitoring change over time, at the level of the facility and at the level of a region or country. We identify problems encountered in the field with data collection and interpretation. RESULT: While they have strengths and weaknesses, the process indicators in general serve the purposes for which they were developed. The data are easily collected, but some data problems were identified. We recommend several relatively minor modifications to improve data collection, interpretation and utility. CONCLUSIONS: The EmOC process indicators have been used successfully in a wide variety of settings. They describe vital elements of the health system and how well that system is functioning for women at risk of dying from major obstetric complications.

Measuring progress towards the MDG for maternal health: including a measure of the health system's capacity to treat obstetric complications.

OBJECTIVE: This paper argues for an additional indicator for measuring progress of the Millennium Development Goal for maternal health-the availability of emergency obstetric care. METHODS: MDG monitoring will be based on two indicators: the maternal mortality ratio and the proportion of births attended by skilled personnel. Strengths and weaknesses of a third indicator are discussed RESULTS: The availability of EmOC measures the capacity of the health system to respond to direct obstetric complications. Benefits to using this additional indicator are its usefulness in determining an adequate distribution of services and showing management at all levels what life-saving interventions are not being provided, and stimulate thought as to why. It can reflect programmatic changes over a relatively short period of time and data requirements are not onerous. CONCLUSION: A measure of strength of the health system is important since many interventions depend on the health system for their implementation.

Global patterns in availability of emergency obstetric care.

OBJECTIVE: This paper examines the availability of basic and comprehensive emergency obstetric care (EmOC), interventions used to treat direct obstetric complications. Determining what interventions are provided in health facilities is the first priority in analyzing a country's capabilities to treat obstetric emergencies. There are eight key interventions, six constitute basic EmOC and all eight comprehensive EmOC. METHODS AND RESULTS: Based on data from 24 needs assessments, the following global patterns emerge: comprehensive EmOC facilities are usually available to meet the recommended minimum number for the size of the population, basic EmOC facilities are consistently not available in sufficient numbers, both in countries with high and moderate levels of maternal mortality, and the majority of facilities offering maternity services provide only some interventions indicating an unrealized potential. CONCLUSION: Upgrading maternities, health centers and hospitals to at least basic EmOC status would be a major contributing step towards maternal mortality reduction in resource-poor countries.

The availability of life-saving obstetric services in developing countries: an in-depth look at the signal functions for emergency obstetric care.

OBJECTIVE: This paper examines the frequency with which a set of life-saving interventions or signal functions was performed to treat major obstetric complications. METHODS AND RESULTS: The basic signal functions include parenteral antibiotics, anticonvulsants and oxytocics, and the procedures of manual removal of the placenta, removal of retained uterine products, and assisted vaginal delivery. Comprehensive functions include the six basic functions, cesarean delivery, and blood transfusions. Data from 1906 health facilities in 13 countries indicate that the most likely functions to be reported are oxytocics and antibiotics. The basic function least likely to be reported is assisted vaginal delivery. Many of the facilities surveyed did not have the infrastructure to perform operations or provide blood transfusions. CONCLUSIONS: These data can help governments allocate their budgets appropriately, help policy makers and planners identify systemic bottlenecks and prioritize solutions. Monitoring the performance of the functions informs us of the capacity of the health system to provide key interventions when obstetric emergencies occur.