It is a central principle in medical ethics that vulnerable patients are entitled to a degree of protection that reflects their vulnerability. In critical care research, this protection is often ...established by means of so‐called proxy consent. Proxy consent for research participation constitutes a substituted judgement by a close relative or friend, based on knowledge of patient's values, preferences, and view of life. For the consent to be genuine, the proxy must be informed of and understand three fundamental aspects of research practice: (1) that participation is voluntary and the consent can be withdrawn at any time; (2) that the research is designed to benefit future patients and society as a whole, and not the individual study participant; and (3) that participation involves an incremental non‐therapeutic risk. If this is not fulfilled because the research is to be conducted under circumstances where the proxy is unavailable, adequate protection of the patient must be ensured by other means. Thus, the research must be designed specifically to benefit critically ill patients, and the incremental non‐therapeutic risk must only comprise a minimal risk.
Carbon-based electronics is a promising alternative to traditional silicon-based electronics as it could enable faster, smaller and cheaper transistors, interconnects and memory devices. However, the ...development of carbon-based memory devices has been hampered either by the complex fabrication methods of crystalline carbon allotropes or by poor performance. Here we present an oxygenated amorphous carbon (a-COx) produced by physical vapour deposition that has several properties in common with graphite oxide. Moreover, its simple fabrication method ensures excellent reproducibility and tuning of its properties. Memory devices based on a-COx exhibit outstanding non-volatile resistive memory performance, such as switching times on the order of 10 ns and cycling endurance in excess of 10(4) times. A detailed investigation of the pristine, SET and RESET states indicates a switching mechanism based on the electrochemical redox reaction of carbon. These results suggest that a-COx could play a key role in non-volatile memory technology and carbon-based electronics.
Objective: To analyse how patients in the acute phase of a myocardial infarct experience the informed consent procedure of a clinical trial. Design: A questionnaire based follow up survey including ...patients who gave informed consent as well as patients who did not consent to the trial. Patients: 103 patients who gave informed consent and 78 who did not consent to the second Danish acute myocardial infarction trial (DANAMI-2). Results: 76% of the trial participants and 63% of the non-participants agreed or mostly agreed that they felt able to make a decision about whether or not to participate in the trial; 50% of the trial participants and 34% of the non-participants found it acceptable that patients in their situation have to make such a decision. Only 28% of the trial participants and 7% of the non-participants read the information sheet before they made the decision. Conclusions: Informed consent should be sought in acute myocardial infarction trials despite the emergency situation and the medical condition of the patients. Patients’ self assessed ability to make a decision should be explicitly addressed during the informed consent process and patients should not be pressurised into decision making. Physicians and research ethics committees should focus specifically on improving the oral information.
Jurassic volcanismin Southern-Central Chile (35°–39°S) is represented mainly by two units. The first characterized by the volcanic and subvolcanic mostly andesitic deposits of the Altos de Hualmapu ...Formation, located in actual Coastal Cordillera (35°–35°30′S) and the second corresponding to the lower basaltic and upper andesitic to dacitic upper member of Nacientes del Biobio Formation, in actual Main Cordillera (39°S). Both units mark the transition between northern and patagonian segments of Early Andean Magmatic Province (EAMP) that reach its maximum magmatic activity in this area during late Middle Jurassic in Coastal Cordillera, after two minor pulses of activity between Upper Triassic and Lower Jurassic. No evidence of arc activity is recorded in this area after 155 Ma, when volcanic axis seems to shift to actual Main Cordillera until Lower Cretaceous when it is resumed again to the west. The discontinuity of the arc front suggest the presence of a major cutoff in axis at ≈36–37°. Whole rock geochemical and isotopical Sr-Nd-Pb data shows that this areal discontinuity coincides with an enrichment of the magmas that suggest ≈20–30% of participation of an enriched source in the genesis of the magmas. Given the mostly extensional to transtensional tectonic regime of Western Gondwana during Jurassic and Lower Cretaceous it is unlike to assume high degrees of assimilation at shallow levels, so the observed enrichment should reflect the addition of fertile asthenospheric mantle dragged by the slab as result of the massive roll back and tearing of the oceanic plate under the Arc in Patagonia during Upper Triassic and Middle Jurassic.
•Southern Central Chile Jurassic magmatism is geochemical and isotopically enriched.•Slab tear influence in Jurassic magmatism of Southern Central Chile.•Main peak of Jurassic arc activity take place during Late Middle Jurassic.•A discontinuity in the arc front position is observed at 36–37°S.•Transition between Central and Patagonian Early Andean Magmatic Province.
Rationing healthcare is a difficult task, which includes preventing patients from accessing potentially beneficial treatments. Proponents of implicit rationing argue that politicians cannot resist ...pressure from strong patient groups for treatments and conclude that physicians should ration without informing patients or the public. The authors subdivide this specific programme of implicit rationing, or “hidden rationing”, into local hidden rationing, unsophisticated global hidden rationing and sophisticated global hidden rationing. They evaluate the appropriateness of these methods of rationing from the perspectives of individual and political autonomy and conclude that local hidden rationing and unsophisticated global hidden rationing clearly violate patients’ individual autonomy, that is, their right to participate in medical decision-making. While sophisticated global hidden rationing avoids this charge, the authors point out that it nonetheless violates the political autonomy of patients, that is, their right to engage in public affairs as citizens. A defence of any of the forms of hidden rationing is therefore considered to be incompatible with a defence of autonomy.
Background: A congenital form of idiopathic intestinal bile acid malabsorption (IBAM) has been associated with dysfunctional mutations in the ileal apical sodium-dependent bile acid transporter ...(ASBT). The aim of this study was to determine whether mutations in the ASBT gene (SLC10A2) predispose to the development of adult-onset idiopathic bile acid malabsorption and chronic watery diarrhea. Methods: Genomic DNA was obtained from 13 adult IBAM patients previously diagnosed on the basis of clinical data, response to cholestyramine, and abnormal 75Se-homocholic acid taurine (SeHCAT) test values. The ASBT gene was screened for the presence of mutations or polymorphisms by single-stranded conformation polymorphism analysis (SSCP) and DNA sequencing. Results: ASBT gene polymorphisms were detected in 5 of the 13 adult IBAM patients. Four patients were heterozygous for a common polymorphism in exon 3, leading to an alanine to serine substitution at codon 171 (A171S). An additional subject was heterozygous for a polymorphism in exon 1 that causes a valine to isoleucine substitution at codon 98 (V98I). These functional polymorphisms were also found in unaffected subjects and do not appear to affect ASBT function. Conclusions: Adult-onset IBAM is not directly related to dysfunctional mutations in the coding region or intron/exon junctions of the SLC10A2 gene. In the absence of apparent ileal disease or intestinal motility defects, inappropriate down-regulation of the ileal bile acid transporter or defects in ileocyte transfer of bile acids into the portal circulation could explain this form of adult IBAM.
Cancer patients demand a high level of involvement in decisions concerning treatment. Many patients are informed about experimental trials, and especially the first consultation may be crucial for ...the future communication and treatment process. Patients with nonresectable non-small-cell lung cancer or colorectal cancer informed about experimental chemotherapy completed a questionnaire on satisfaction with the communication process, general attitude towards experimental treatments, the substance of information, and personal contact with the physician following their first consultation in a medical oncology unit. Physicians completed a questionnaire on their perception of the patients' satisfaction. Among 68 physician-cancer patient pairs, 29 patients were informed on chemotherapy in randomised trials and 39 in nonrandomised studies. The general attitude towards experimental treatment was positive or very positive in 71% of patients. Information on the treatment was perceived as completely adequate in 93% of patients informed on randomised and in 67% informed on nonrandomised trials. Physicians underestimated the patients' satisfaction with the overall communication process, the personal contact, the patients' perceived sufficiency of the specific treatment information and their ability to decide on study entry. In conclusion, considerable differences were observed between patients informed about experimental chemotherapy in randomised and nonrandomised trials, both with respect to their perception of how adequate the information on the specific treatments were, and whether it was sufficient for decisions on study entry. This study type effect should be accounted for in future evaluations of communication and patient satisfaction. The data also support the fact that cancer patients have a desire for and ability to understand rather detailed and comprehensive treatment information.
Background: Visceral hyperalgesia is most likely a phenomenon of substantial clinical importance and may also play a role in the pathophysiology of the irritable bowel syndrome (IBS). We investigated ...the manifestation of visceral hyperalgesia in IBS patients by nociceptive electric stimulation of the rectosigmoid junction and rectum. Methods: Twelve IBS patients fulfilling the Rome criteria and 9 healthy controls were studied. Visceral single and repeated electric burst stimuli were applied with a bipolar electric stimulator inserted through the sigmoidoscope. The sensation (ST) and pain detection (PDT) thresholds were determined in response to single and repeated stimuli at the rectosigmoid junction, and PDT to repeated stimuli at four different positions in the rectum. Cutaneous single and repeated electric stimuli were applied to the lateral aspect of the foot, determining ST and PDT. Results: Cutaneous stimulation showed no significant differences for ST and PDT between patients and controls. The rectosigmoid junction showed significantly lower ST for single stimuli (P < 0.01) and a significantly lower PDT for single and for repeated stimuli (P < 0.05 and P < 0.02) in IBS patients. In the rectum the IBS patients had a significantly lower PDT than controls (P < 0.001). Conclusions: For cutaneous electric stimulation no differences in the pain thresholds between the two groups were found, showing that there is no generalized hyperalgesia in IBS patients. The IBS patients had a specific decrease of the pain thresholds in the rectum and rectosigmoid junction, indicating visceral hyperalgesia. These results point to central visceral hyperexcitability as an important factor in the pathophysiology of IBS.
Background: From 1986 to 1993, 150 patients were investigated with the 75Se-homocholic acid taurine (SeHCAT) test as a late step in the investigation of chronic diarrhoea. On basis of low SeHCAT ...values and response to cholestyramine treatment, 33 patients were initially classified as having idiopathic bile acid malabsorption (IBAM). The aim was to describe the long-term clinical course of the disease and to assess the reliability of the SeHCAT test in diagnosing IBAM. Methods: The methods included 1) clinical follow-up with patient interview combined with information from medical records and 2) repeated SeHCAT test. Results: The diagnosis of IBAM had to be revised in three cases (inflammatory bowel disease in two patients, Clostridium difficile infection in one). Six patients were lost to follow-up and a further four patients were excluded from re-examination either because of old age (>80 years) or bowel resection, leaving 20 patients for re-examination, of which 16 completed both clinical follow-up and a new SeHCAT test. The median duration of symptoms before initial SeHCAT test was 2.5 (1-30) years. In 13 of 16 patients symptoms persisted, and SeHCAT values remained low and almost identical to the initial value after a median observation time of 88 (51-113) months. Despite initial response to treatment with cholestyramine, six patients had to discontinue treatment because of adverse effects or other compliance problems. In three patients the SeHCAT value showed a considerable increase, and bowel function had correspondingly normalized in these cases. Conclusion: The study confirms the reliability of the SeHCAT test in diagnosing IBAM. Despite adult onset of symptoms, only a few patients improve after several years' observation. Treatment with cholestyramine is generally effective but not always tolerated.
The Maipo Transition Zone or Maipo Orocline represents a change in strike of the topography from N–S between 30° and 33°S to an NNE-SSW trend to the south. The southern flank of the Maipo Orocline ...can be traced along strike to around 38°S. There the Andean margin exposes another orogen bending, the Arauco Orocline. Although the tectonic evolution of this segment of the Andean chain is relatively well constrained, the limit between both oroclines is unclear. In this paper, we show the results of a paleomagnetic study carried out in three plutons of Upper Triassic age located along the Coastal Cordillera of central Chile between 35° and 37°S. Paleomagnetic analysis from Constitución Granite and Cobquecura Pluton shows an increase of clockwise vertical-axis rotations from north to south consistent with previous data, whereas results obtained in the Hualpén Stock, located to the south, shows minors counter-clockwise rotations. This change in the rotation pattern would reflect the Maipo and Arauco Oroclines limit. The similar amounts of tectonic rotations recorded by Mesozoic and Miocene rocks indicate that the whole area behaved as a single block and constrains the maximum possible age for the occurrence of tectonic rotations to Miocene.
•Paleomagnetic data from Upper Triassic rocks in southern Chile is presented.•Vertical-axis rotations related to Maipo Orocline formation are recorded.•The boundary between the Maipo and Arauco oroclines is located north of Hualpén Stock.
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