Recording problems and diagnoses in clinical care: developing guidance for healthcare professionals and system designers

BACKGROUND: Accurate recording of problems and diagnoses in health records is key to safe and effective patient care, yet it is often done poorly. Electronic health record systems vary in their functionality and ease of use, and are not optimally designed for easy recording and sharing of clinical information. There is a lack of professional consensus and guidance on how problems and diagnoses should be recorded. METHODS: The Professional Record Standards Body commissioned work led by the Royal College of Physicians Health Informatics Unit to carry out a literature review, draft guidance, carry out an online consultation and round table discussion, and produce a report including recommendations for systems. A patient workshop was held to explore patient preferences for mechanisms for sharing diagnosis information between primary and secondary care. RESULTS: Consensus was reached among medical specialties on key elements of diagnosis recording, and draft guidance was produced ready for piloting in a variety of care settings. Patients were keen for better ways for diagnosis information to be shared. DISCUSSION: Improving the recording of diagnoses and problems will require a major effort of which the new guidance is only a part. The guidance needs to be embedded in training, and clinical systems need to have improved, standardised functionality. Front-line clinicians, specialist societies, clinical informaticians and patients need to be engaged in developing information models for diagnoses to support care and research, accessible via user-friendly interfaces

Gamma-Ray Bursts in the Swift Era

With its rapid-response capability and multiwavelength complement of instruments, the Swift satellite has transformed our physical understanding of gamma-ray bursts (GRBs). Providing high-quality observations of hundreds of bursts, and facilitating a wide range of follow-up observations within seconds of each event, Swift has revealed an unforeseen richness in observed burst properties, shed light on the nature of short-duration bursts, and helped realize the promise of GRBs as probes of the processes and environments of star formation out to the earliest cosmic epochs. These advances have opened new perspectives on the nature and properties of burst central engines, interactions with the burst environment from microparsec to gigaparsec scales, and the possibilities for non-photonic signatures. Our understanding of these extreme cosmic sources has thus advanced substantially; yet more than 40 years after their discovery, GRBs continue to present major challenges on both observational and theoretical fronts.Comment: 67 pages, 16 figures; ARAA, 2009; http://arjournals.annualreviews.org/toc/astro/47/

Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival

A delay in the completion of metaphase induces a stress response that inhibits further cell proliferation or induces apoptosis. This response is thought to protect against genomic instability and is important for the effects of anti-mitotic cancer drugs. Here, we show that mitotic arrest induces a caspase-dependent DNA damage response (DDR) at telomeres in non-apoptotic cells. This pathway is under the control of Mcl-1 and other Bcl-2 family proteins and requires caspase-9, caspase-3/7 and the endonuclease CAD/DFF40. The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a DDR that involves DNA-dependent protein kinase (DNA-PK). Suppression of mitotic telomere damage by enhanced expression of TRF2, or the inhibition of either caspase-3/7 or DNA-PK during mitotic arrest, promotes subsequent cell survival. Thus, we demonstrate that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling, and determines cell fate in response to a prolonged delay in mitosis

Validation of a chloroquine-induced cell death mechanism for clinical use against malaria

An alternative antimalarial pathway of an ‘outdated’ drug, chloroquine (CQ), may facilitate its return to the shrinking list of effective antimalarials. Conventionally, CQ is believed to interfere with hemozoin formation at nanomolar concentrations, but resistant parasites are able to efflux this drug from the digestive vacuole (DV). However, we show that the DV membrane of both resistant and sensitive laboratory and field parasites is compromised after exposure to micromolar concentrations of CQ, leading to an extrusion of DV proteases. Furthermore, only a short period of exposure is required to compromise the viability of late-stage parasites. To study the feasibility of this strategy, mice malaria models were used to demonstrate that high doses of CQ also triggered DV permeabilization in vivo and reduced reinvasion efficiency. We suggest that a time-release oral formulation of CQ may sustain elevated blood CQ levels sufficiently to clear even CQ-resistant parasites

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy

We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (GRIPS) mission addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate $\gamma$-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.Comment: to appear in Exp. Astron., special vol. on M3-Call of ESA's Cosmic Vision 2010; 25 p., 25 figs; see also www.grips-mission.e

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

A Blast Wave from the 1843 Eruption of Eta Carinae

Very massive stars shed much of their mass in violent precursor eruptions as luminous blue variables (LBVs) before reaching their most likely end as supernovae, but the cause of LBV eruptions is unknown. The 19th century eruption of Eta Carinae, the prototype of these events, ejected about 12 solar masses at speeds of 650 km/s, with a kinetic energy of almost 10^50 ergs. Some faster material with speeds up to 1000-2000 km/s had previously been reported but its full distribution was unknown. Here I report observations of much faster material with speeds up to 3500-6000 km/s, reaching farther from the star than the fastest material in earlier reports. This fast material roughly doubles the kinetic energy of the 19th century event, and suggests that it released a blast wave now propagating ahead of the massive ejecta. Thus, Eta Car's outer shell now mimics a low-energy supernova remnant. The eruption has usually been discussed in terms of an extreme wind driven by the star's luminosity, but fast material reported here suggests that it was powered by a deep-seated explosion rivalling a supernova, perhaps triggered by the pulsational pair instability. This may alter interpretations of similar events seen in other galaxies.Comment: 10 pages, 3 color figs, supplementary information. Accepted by Natur

Cytokeratin expression during mouse embryonic and early postnatal mammary gland development

Cytokeratins are intermediate filament proteins found in most epithelial cells including the mammary epithelium. Specific cytokeratin expression has been found to mark different epithelial cell lineages and also to associate with putative mammary stem/progenitor cells. However, a comparative analysis of the expression of cytokaratins during embryonic and postnatal mammary development is currently lacking. Moreover, it is not clear whether the different classes of putative mammary stem/progenitor cells exist during embryonic development. Here, we use double/triple-label immunofluorescence and immunohistochemistry to systematically compare the expression of cytokeratin 5 (K5), cytokeratin 6 (K6), cytokeratin 8 (K8), cytokeratin 14 (K14) and cytokeratin 19 (K19) in embryonic and early postnatal mouse mammary glands. We show that K6+ and K8+/K14+ putative mammary progenitor cells arise during embryogenesis with distinct temporal and spatial distributions. Moreover, we describe a transient disconnection of the expression of K5 and K14, two cytokeratins that are often co-expressed, during the first postnatal weeks of mammary development. Finally, we report that cytokeratin expression in cultured primary mammary epithelial cells mimics that during the early stages of postnatal mammary development. These studies demonstrate an embryonic origin of putative mammary stem/progenitor cells. Moreover, they provide additional insights into the use of specific cytokeratins as markers of mammary epithelial differentiation, or the use of their promoters to direct gene overexpression or ablation in genetic studies of mouse mammary development