In 2006, a consensus concerning functional gastrointestinal intestinal disorders in infants and toddlers was described. At that time, little evidence regarding epidemiology, pathophysiology, ...diagnostic workup, treatment strategies, and follow-up was available. Consequently, the criteria for the clinical entities were more experience based than evidence based. In the past decade, new insights have been gained about the different functional gastrointestinal intestinal disorders in these age groups. Based on those, further revisions have been made to the criteria. The description of infant colic has been expanded to include criteria for the general pediatrician and specific criteria for researchers. The greatest change was the addition of a paragraph regarding the neurobiology of pain in infants and toddlers, including the understanding of the neurodevelopment of nociception and of the wide array of factors that can impact the pain experience.
•NLP can generate meaningful information from healthcare incident reports.•In classification tasks, NLP can perform well compared to manual annotation.•No single NLP technique shows superiority in ...this domain.•NLP has the potential to improve learning from adverse events in healthcare.
Adverse events in healthcare are often collated in incident reports which contain unstructured free text. Learning from these events may improve patient safety. Natural language processing (NLP) uses computational techniques to interrogate free text, reducing the human workload associated with its analysis. There is growing interest in applying NLP to patient safety, but the evidence in the field has not been summarised and evaluated to date.
To perform a systematic literature review and narrative synthesis to describe and evaluate NLP methods for classification of incident reports and adverse events in healthcare.
Data sources included Medline, Embase, The Cochrane Library, CINAHL, MIDIRS, ISI Web of Science, SciELO, Google Scholar, PROSPERO, hand searching of key articles, and OpenGrey. Data items were manually abstracted to a standardised extraction form.
From 428 articles screened for eligibility, 35 met the inclusion criteria of using NLP to perform a classification task on incident reports, or with the aim of detecting adverse events. The majority of studies used free text from incident reporting systems or electronic health records. Models were typically designed to classify by type of incident, type of medication error, or harm severity. A broad range of NLP techniques are demonstrated to perform these classification tasks with favourable performance outcomes. There are methodological challenges in how these results can be interpreted in a broader context.
NLP can generate meaningful information from unstructured data in the specific domain of the classification of incident reports and adverse events. Understanding what or why incidents are occurring is important in adverse event analysis. If NLP enables these insights to be drawn from larger datasets it may improve the learning from adverse events in healthcare.
It is entirely fitting that Erik Roraback’s book on community and the creative life should have as its greatest strength its own creative and highly original style, vision, and power of comparative ...perspective and synthesis. The vision and comparative perspective are broad indeed bringing together a wide range of canonical theoretical, philosophical, and literary figures and texts as well as popular culture references, specifically from the world of tennis. Thus Spinoza, Gilles Deleuze, and Ž...
Background:
Ketamine is emerging as an effective, rapidly acting antidepressant in adult research. Hypothetical concerns about its long-term safety and impact on the developing brain are limiting its ...research in children. However, a wealth of paediatric safety and dosing data exists for ketamine, given its extensive use globally as an anaesthetic, analgesic and sedative agent.
Aims:
To evaluate the safety of repeat dosing of ketamine in children.
Methods:
A systematic search of EMBASE, MEDLINE, PsycINFO, Cochrane Library and PubMed from inception to 13 April 2023 was conducted. Included studies were those reporting adverse events when ketamine was given repeatedly to children aged 5–18, for any condition. No language restrictions were applied. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline and Joanna Briggs Institute Critical Appraisal Tools Checklist for study quality assessment were used. The review process was performed independently by two reviewers.
Results:
Five observational studies (87 patients) were included. The maximum number of doses per patient was 42, over a maximum of 4 months. There were no serious adverse events. There was no evidence of needing higher doses with time to indicate tolerance. The longest follow-up period was 6 months. There were no long-term consequences (including neurocognitive) reported within this time frame.
Conclusions:
These results suggest that, despite methodological limitations of the studies, ketamine is well tolerated and safe for use in children, even when given repeatedly in regimens analogous to those used for the treatment of depression in adults. This finding supports the expansion of research into the use of ketamine as a novel antidepressant in children.
The 2016 M7.8 Kaikōura (New Zealand) earthquake struck the east coast of the northern South Island, resulting in strong ground shaking and large surface fault slip. Since the earthquake was well ...recorded by a local strong‐motion seismic network, near‐fault data may provide direct measurements of dynamic parameters associated with the fault‐weakening process. Here we estimate a proxy for slip‐weakening distance
Dc′′, defined as double the fault‐parallel displacement at the time of peak ground velocity, from accelerograms recorded at a near‐fault station. Three‐component ground displacements were recovered from the double numerical integration of accelerograms, and the corresponding final displacements are validated against coseismic displacement from geodetic data. The estimated
Dc′′ is 4.9 m at seismic station KEKS located ∼2.7 km from a segment of the Kekerengu fault where large surface fault slip (∼12 m) has been observed. The inferred
Dc′′ is the largest value ever estimated from near‐fault strong motion data, yet it appears to follow the scaling of
Dc′′ with final slip for several large strike‐slip earthquakes. The energy budget of the M7.8 Kaikōura earthquake inferred from the scaling of
Dc′′ with final slip indicates that a large amount of energy was dissipated by on‐ and off‐fault inelastic deformation during the propagation of the earthquake rupture, resulting in a slower average rupture speed (
≲2.0 km/s).
Plain Language Summary
Slip‐weakening distance is a parameter controlling the evolution of fault slip during an earthquake and is important for understanding rupture dynamics. However, it has been debated how large slip‐weakening distance is and whether it scales with fault slip. We present evidence for large slip‐weakening distance estimated from near‐fault record of the recent magnitude 7.8 Kaikōura (New Zealand) earthquake. By examining seismic waveforms of the Kaikōura quake, we find that the slip‐weakening distance is about 5 m on a portion of the Kekerengu fault, the largest value ever estimated directly from near‐fault records. The large slip‐weakening distance implies that a large amount of energy was dissipated by on‐ and off‐fault inelastic deformation during the propagation of earthquake rupture, which may explain why the rupture propagation velocity of the Kaikōura quake was slower than that of most crustal earthquakes.
Key Points
We estimate a proxy for slip‐weakening distance
Dc′′ from near‐fault record of the 2016 M7.8 Kaikōura (New Zealand) earthquake
The
Dc′′ is 4.9 m at station KEKS, the largest value ever estimated from near‐fault strong motion data
The large
Dc′′ appears to follow the scaling
Dc′′ with final slip for several large strike‐slip earthquakes
Materials for electrochemical ammonia synthesis McPherson, Ian James; Sudmeier, Tim; Fellowes, Joshua ...
Dalton transactions : an international journal of inorganic chemistry,
02/2019, Letnik:
48, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Direct electrochemical synthesis of ammonia is proposed as a means of reducing the carbon footprint of the fertiliser industry, as well as providing new opportunities for carbon-free liquid energy ...storage. We review the current status of research into materials for electrochemical ammonia synthesis and evaluate the reported rates and efficiencies in terms of recent US Department of Energy targets. Surprisingly, development of electrocatalysts has only recently received much attention, and despite a number of promising rates, the target values remain distant. A number of theoretical studies suggest a range of candidate materials yet to be explored.
Direct electrochemical synthesis of ammonia is proposed as a means of reducing the carbon footprint of the fertiliser industry, as well as providing new opportunities for carbon-free liquid energy storage.
•HER3 is associated with tumor development, resistance and poor clinical prognosis in different cancers.•HER3-targeting agents have been undergoing clinical evaluation for the last 10 years in ...clinical phase 1 and 2 studies.•Combinations of HER3-binding antibodies with other HER-targeting therapies or chemotherapies have been pursued in various solid tumors.•HER3 and heregulin have been identified as potential response prediction markers.•Inhibition of HER3 has not yet resulted in any meaningful clinical efficacy in the treatment of solid tumors.
The human epidermal growth factor receptor (HER) family consists of four transmembrane receptor tyrosine kinases: epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. They are part of a complex signalling network and stimulate intracellular pathways regulating cell growth and differentiation. So far, monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors targeting EGFR and HER2 have been developed and approved. Recently, focus has turned to HER3 as it may play an important role in resistance to EGFR- and HER2-targeting therapies. HER3-targeting agents have been undergoing clinical evaluation for the last 10 years and currently thirteen mAbs are in phase 1 or 2 clinical studies. Single agent activity has proven to be limited, however, the tolerability was favourable. Thus, combinations of HER3-binding mAbs with other HER-targeting therapies or chemotherapies have been pursued in various solid tumor entities. Data indicate that the HER3-binding ligand heregulin may serve as a response prediction marker for HER3-targeting therapy. Within this review the current status of clinical development of HER3-targeting compounds is described.
Linda Martín Alcoff and others have emphasised that the discipline of philosophy suffers from a ‘demographic problem’. The persistence of this problem is partly the consequence of various forms of ...resistance to efforts to address the demographic problem. Such resistance is complex and takes many forms and could be responded to in different ways. In this paper, I argue that our attempts to explain and understand the phenomenon of resistance should use a kind of explanatory pluralism that, following Quassim Cassam, I call multidimensionalism. I describe four general kinds of resistance and consider varying explanations, focusing on those focused on vices and social structures. I argue that vice-explanations and structural- explanations are both mutually consistent and mutually entailing. If so, there is no need to choose between vice explanations and structural explanations or any other kinds of explanation. We can and should be multidimensionalists: using many together is better.
Linda Martín Alcoff i drugi naglasili su da filozofija kao disciplina pati od "demografskog problema". Upornost ovog problema djelomično je posljedica različitih oblika otpora nastojanjima da se riješi demografski problem. Takav otpor je složen i pojavljuje se u mnogim oblicima te se na njega može odgovoriti na različite načine. U ovom radu tvrdim da bi naši pokušaji objašnjenja i razumijevanja fenomena otpora trebali koristiti pluralističko objašnjenje koje, prema Quassimu Cassamu, nazivam višedimenzionalizam. Opisujem četiri opća oblika otpora i razmatram različita objašnjenja, usredotočujući se na one koji su usmjereni na mane i društvene strukture. Tvrdim da su objašnjenja utemeljena na porocima i strukturalna objašnjenja međusobno usklađena i da se međusobno impliciraju. Ako je tome tako, nema potrebe birati između objašnjenja utemeljenih na porocima i strukturalnih objašnjenja ili bilo kojih drugih vrsta objašnjenja. Možemo i trebali bismo biti višedimenzionalisti: upotreba mnogih zajedno je bolja.
Biomarker studies have shown that expression of the T-cell coregulatory ligand PDL1 on tumor cells correlates with clinical responsiveness to the PD1 antibody nivolumab. Here, we report the findings ...of a preclinical cancer vaccine study demonstrating vaccine-dependent PDL1 upregulation in the tumor microenvironment. We formulated an IFNγ-inducing cancer vaccine called TEGVAX that combined GM-CSF and multiple Toll-like receptor agonists to increase the number of activated dendritic cells. Treatment of established tumors with TEGVAX retarded tumor growth in a manner associated with enhanced systemic antitumor immunity. Unexpectedly, TEGVAX also upregulated PDL1 expression in the tumor microenvironment, possibly explaining why tumors were not eliminated completely. In support of this likelihood, PDL1 upregulation in this setting relied upon IFNγ-expressing tumor-infiltrating CD4(+) and CD8(+) T cells and administration of a PD1-blocking antibody with TEGVAX elicited complete regression of established tumors. Taken together, our findings provide a mechanistic rationale to combine IFNγ-inducing cancer vaccines with immune checkpoint blockade.
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