Basal cell nuclear size in experimental oral mucosal carcinogenesis.

It has been suggested that the size of the nuclei of epithelial basal cells can be used in predicting the likelihood of malignant transformation of epithelium. This proposition was assessed in rat palatal epithelium after the carcinogen 4-nitroquinoline-1-oxide had been applied to the epithelium for varying periods of time. No consistent alterations in basal cell nuclear size, including area, perimeter, diameter and regularity of form were found with routine light microscopy as the epithelium passed through various stages of dysplasia to carcinoma. This finding casts doubt on the value of using a variation of basal cell nuclear size as a predictor of malignant transformation

The impact of advance care planning on end of life care in elderly patients: randomised controlled trial

Objective To investigate the impact of advance care planning on end of life care in elderly patients

The Will to Prevail: Inside the Legal Battle to Save Sweet Briar

Part I provides an in-depth factual overview, beginning with the Sweet Briar College\u27s founding in the early 1900s. The commentary then turns to the controversial decision to close and discusses the facts and legal theories of the case, the decisions by the circuit court and the Supreme Court of Virginia, and the eventual settlement that kept the school alive. In Part II, the discussion shifts to the landmark nature of this case, not only for Sweet Briar College, but also for other Virginia colleges and non-profits around the country. The essay analyzes the legal questions arising from the case, including whether a Virginia corporation could also be a trustee, and, what were the Board\u27s legal obligations in this case

Phase I/II study of DHA–paclitaxel in combination with carboplatin in patients with advanced malignant solid tumours

DHA–paclitaxel is a conjugate of paclitaxel and the fatty acid, docosahexaenoic acid. Preclinical studies have demonstrated increased activity, relative to paclitaxel, with the potential for an improved therapeutic ratio. We conducted a phase I study to determine the maximum tolerated doses of DHA–paclitaxel and carboplatin when administered in combination. Two cohorts of patients were treated: carboplatin AUC 5 with DHA–paclitaxel 660 mg m-2 and carboplatin AUC 5 with DHA–paclitaxel 880 mg m-2. Both drugs were given on day 1 every 21 days. A total of 15 patients were enrolled with a median age of 59 years (range 33–71). All patients had advanced cancer refractory to standard treatment, performance status 0–2 and were without major organ dysfunction. A total of 54 cycles of treatment were delivered. No dose-limiting toxicity (DLT) was seen in the first cohort of three patients. In an expanded second cohort, neutropenia was the main DLT, occurring in the first cycle of treatment in five of 12 patients: three of these patients and one additional patient also experienced dose-limiting grade 3 transient rises in liver transaminases. No alopecia was seen and one patient developed clinically significant neuropathy. One partial response was seen in a patient with advanced adenocarcinoma of the oesophago-gastric junction and 12 patients had stable disease with a median time to progression of 184 days (range 60–506 days). The recommended phase II dose in pretreated patients is Carboplatin AUC 5 and DHA–paclitaxel 660 mg m-2 given every 21 days. Further studies with Carboplatin AUC 5 and DHA-paclitaxel 880 mg m-2, given every 28 days, are warranted in chemo-naive patients

Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest

Introduction: Hyperoxia has recently been reported as an independent risk factor for mortality in patients resuscitated from cardiac arrest. We examined the independent relationship between hyperoxia and outcomes in such patients.Methods: We divided patients resuscitated from nontraumatic cardiac arrest from 125 intensive care units (ICUs) into three groups according to worst PaOlevel or alveolar-arterial Ogradient in the first 24 hours after admission. We defined 'hyperoxia' as PaOof 300 mmHg or greater, 'hypoxia/poor Otransfer' as either PaO 400 mmHg, hyperoxia had no independent association with mortality. Importantly, after adjustment for FiOand the relevant covariates, PaOwas no longer predictive of hospital mortality (P = 0.21).Conclusions: Among patients admitted to the ICU after cardiac arrest, hyperoxia did not have a robust or consistently reproducible association with mortality. We urge caution in implementing policies of deliberate decreases in FiOin these patients

Laboratory earthquake forecasting. A machine learning competition

Earthquake prediction, the long-sought holy grail of earthquake science, continues to confound Earth scientists. Could we make advances by crowdsourcing, drawing from the vast knowledge and creativity of the machine learning (ML) community? We used Google’s ML competition platform, Kaggle, to engage the worldwide ML community with a competition to develop and improve data analysis approaches on a forecasting problem that uses laboratory earthquake data. The competitors were tasked with predicting the time remaining before the next earthquake of successive laboratory quake events, based on only a small portion of the laboratory seismic data. The more than 4,500 participating teams created and shared more than 400 computer programs in openly accessible notebooks. Complementing the now well-known features of seismic data that map to fault criticality in the laboratory, the winning teams employed unexpected strategies based on rescaling failure times as a fraction of the seismic cycle and comparing input distribution of training and testing data. In addition to yielding scientific insights into fault processes in the laboratory and their relation with the evolution of the statistical properties of the associated seismic data, the competition serves as a pedagogical tool for teaching ML in geophysics. The approach may provide a model for other competitions in geosciences or other domains of study to help engage the ML community on problems of significance

Self-organized current transport through low angle grain boundaries in YBa2_2Cu3_3O7−δ_{7-\delta} thin films, studied magnetometrically

The critical current density flowing across low angle grain boundaries in YBa$_2$Cu$_3$O$_{7-\delta}$ thin films has been studied magnetometrically. Films (200 nm thickness) were deposited on SrTiO$_3$ bicrystal substrates containing a single [001] tilt boundary, with angles of 2, 3, 5, and 7 degrees, and the films were patterned into rings. Their magnetic moments were measured in applied magnetic fields up to 30 kOe at temperatures of 5 - 95 K; current densities of rings with or without grain boundaries were obtained from a modified critical state model. For rings containing 5 and 7 degree boundaries, the magnetic response depends strongly on the field history, which arises in large part from self-field effects acting on the grain boundary.Comment: 8 pages, including 7 figure

Bench-to-bedside review: The evaluation of complex interventions in critical care

Complex interventions, such as the introduction of medical emergency teams or an early goal-directed therapy protocol, are developed from a number of components that may act both independently and inter-dependently. There is an emerging body of literature advocating the use of integrated complex interventions to optimise the treatment of critically ill patients. As with any other treatment, complex interventions should undergo careful evaluation prior to widespread introduction into clinical practice. During the development of an international collaboration of researchers investigating protocol-based approaches to the resuscitation of patients with severe sepsis, we examined the specific issues related to the evaluation of complex interventions. This review outlines some of these issues. The issues specific to trials of complex interventions that require particular attention include determining an appropriate study population and defining current treatments and outcomes in that population, defining the study intervention and the treatment to be used in the control group, and deploying the intervention in a standardised manner. The context in which the research takes place, including existing staffing levels and existing protocols and procedures, is crucial. We also discuss specific details of trial execution, in particular randomization, blinded outcome adjudication and analysis of the results, which are key to avoiding bias in the design and interpretation of such trials

Poverty and the multiple stakeholder challenge for global leaders

The article presents a case study in which business leaders deal with challenging problems related to poverty, involving multiple stakeholders. This emphasizes the importance of training prospective global leaders to manage stakeholder relationships and engage in stakeholder dialogue. The authors highlight the stakeholder role played by nongovernmental organizations and include a simulation that develops stakeholder dialogue skills. They identify practical lessons and assumptions underlying business education that are not shared by all stakeholders in the context of poverty