Temperature-resilient solid-state organic artificial synapses for neuromorphic computing.

Devices with tunable resistance are highly sought after for neuromorphic computing. Conventional resistive memories, however, suffer from nonlinear and asymmetric resistance tuning and excessive write noise, degrading artificial neural network (ANN) accelerator performance. Emerging electrochemical random-access memories (ECRAMs) display write linearity, which enables substantially faster ANN training by array programing in parallel. However, state-of-the-art ECRAMs have not yet demonstrated stable and efficient operation at temperatures required for packaged electronic devices (~90°C). Here, we show that (semi)conducting polymers combined with ion gel electrolyte films enable solid-state ECRAMs with stable and nearly temperature-independent operation up to 90°C. These ECRAMs show linear resistance tuning over a >2× dynamic range, 20-nanosecond switching, submicrosecond write-read cycling, low noise, and low-voltage (±1 volt) and low-energy (~80 femtojoules per write) operation combined with excellent endurance (>109 write-read operations at 90°C). Demonstration of these high-performance ECRAMs is a fundamental step toward their implementation in hardware ANNs.

A voltage-gated ion channel expressed specifically in spermatozoa.

Calcium ions play a primary role in the regulation of sperm cell behavior. We report finding a voltage-gated ion channel (CatSper2) that is expressed in male germ cells but not in other cells. The putative channel contains 6 transmembrane segments, making it more similar to the voltage-gated potassium channels, but the ion selectivity pore domain sequence resembles that of a Ca(v) channel. The mRNA is expressed during the meiotic or postmeiotic stages of spermatogenesis, and the protein is localized to the sperm flagellum, suggesting a role in the regulation of sperm motility. The mRNA for the channel is present in mouse, rat, and human sperm cells, and the gene is found on chromosome 2 E5-F1 in the mouse and 15q13 in the human. Recently, another voltage-gated channel (CatSper) that has features similar to the one reported here was discovered. It also is expressed within the flagellum and is required for normal fertility of mice. However, expression of CatSper2 alone or coexpression with CatSper in cultured cells, or attempts to coimmunoprecipitate the two proteins from germ cells failed to demonstrate that these two unique but similar alpha-like subunits form either a homo- or heterotetramer. It is possible, therefore, that two independent alpha subunits, different from other known voltage-gated channels, regulate sperm motility.

Succinylcholine-induced hyperkalemia in a patient with mucositis secondary to chemotherapy.

OBJECTIVE: To report a case of fatal hyperkalemia owing to succinylcholine administration in a patient with mucositis secondary to chemotherapy. DESIGN: Case report. SETTING: Adult intensive care unit (ICU) at Dartmouth-Hitchcock Medical Center. PATIENTS: One patient with mucositis secondary to chemotherapy. MEASUREMENTS AND MAIN RESULTS: A 37-yr-old female with recently diagnosed acute myelogenous leukemia was admitted to the ICU with mental status changes and progressive dyspnea requiring intubation and mechanical ventilation. Before ICU admission, the patient had suffered from painful mucositis causing severe dysphagia and bleeding, which was thought to be the result of chemotherapy. By the 10th ICU day, the patient's respiratory and mental status improved and the patient was successfully extubated. However, 8 hrs after extubation, she gradually developed severe respiratory distress, requiring reintubation and mechanical ventilation. The patient was given 14 mg of etomidate and 100 mg of succinylcholine intravenously. Immediately after the intubation, she suffered cardiac arrest. Her serum potassium level was 13.1 mEq/L and HCO3- was 16 mEq/L. The resuscitation attempt was unsuccessful, and the patient was pronounced dead. CONCLUSION: Oral mucositis is a frequent and potentially severe complication of cancer chemotherapy. We believe that mucositis was a contributing factor to this case of fatal hyperkalemia after administration of succinylcholine, with a mechanism similar to that reported with thermal injury. Only nondepolarizing muscle relaxants should be used in patients who are at risk for mucositis. Mucositis should be added to the list of conditions in which succinylcholine is contraindicated.

Seven legal barriers to end-of-life care: myths, realities, and grains of truth.

OBJECTIVE: The American College of Physicians-American Society of Internal Medicine (ACP-ASIM) End-of-Life Care Consensus Panel was convened in 1997 to identify clinical, ethical, and policy problems in end-of-life care, to analyze critically the available evidence and guidelines, and to offer consensus recommendations on how to improve care of the dying. Topic selection and content presentation were carefully debated to maximize the project's focus on providing practical clinical and other guidance to clinicians who are not specialists in palliative care. This statement examines current legal myths, realities, and grains of truth in end-of-life care. PARTICIPANTS: The Consensus Panel comprises 13 medical and bioethics experts, clinicians, and educators in care at the end of life selected by the Ethics and Human Rights Committee, College leadership, and the Center for Ethics and Professionalism at the ACP-ASIM. EVIDENCE: A literature review including a MEDLINE search of articles from 1970-1998 and review of end-of-life care literature and organizational bibliographies was conducted. Unpublished sources were also identified by participants, as was anecdotal clinical experience. CONSENSUS PROCESS: The draft statement was debated by panel members over a series of 3 to 4 meetings. For this statement, the initial draft and subsequent revised drafts were discussed in 1998-1999. The statement then underwent external peer review and revision before panel approval and the journal peer review process. CONCLUSIONS: Legal myths about end-of-life care can undermine good care and ethical medical practice. In addition, at times ethics, clinical judgment, and the law conflict. Patients (or families) and physicians can find themselves considering clinical actions that are ethically appropriate, but raise legal concerns. The 7 major legal myths regarding end-of-life care are: (1) forgoing life-sustaining treatment for patients without decision-making capacity requires evidence that this was the patient's actual wish; (2) withholding or withdrawing of artificial fluids and nutrition from terminally ill or permanently unconscious patients is illegal; (3) risk management personnel must be consulted before life-sustaining medical treatment may be terminated; (4) advance directives must comply with specific forms, are not transferable between states, and govern all future treatment decisions; oral advance directives are unenforceable; (5) if a physician prescribes or administers high doses of medication to relieve pain or other discomfort in a terminally ill patient, resulting in death, he/she will be criminally prosecuted; (6) when a terminally ill patient's suffering is overwhelming despite palliative care, and he/she requests a hastened death, there are no legally permissible options to ease suffering; and (7) the 1997 Supreme Court decisions outlawed physician-assisted suicide. Many legal barriers to end-of-life care are more mythical than real, but sometimes there is a grain of truth. Physicians must know the law of the state in which they practice. JAMA. 2000;284:2495-2501.

Perspectives on care at the close of life. Initiating end-of-life discussions with seriously ill patients: addressing the "elephant in the room".

Discussions about end-of-life issues are difficult for clinicians to initiate. Patients, their families, and clinicians frequently collude to avoid mentioning death or dying, even when the patient's suffering is severe and prognosis is poor. In addition to determining from observational research when and where communication problems exist, much can be learned from in-depth discussions with patients, family members, and physicians who are facing these issues together. Using segments of interviews with a patient with advanced pulmonary fibrosis, his son, and his primary care physician, this article illustrates and explores some of these communication issues, including the who, what, when, why, and how of end-of-life discussions. Studies from the medical literature, the patient's and physician's particular experience together, and the author's clinical experience provide practical insights into how to address these issues. Initiating end-of-life discussions earlier and more systematically could allow patients to make more informed choices, achieve better palliation of symptoms, and have more opportunity to work on issues of life closure. JAMA. 2000;284:2502-2507.

Palliative treatments of last resort: choosing the least harmful alternative. University of Pennsylvania Center for Bioethics Assisted Suicide Consensus Panel.

Comprehensive palliative care, as exemplified by many state-of-the-art hospice programs, is the standard of care for the dying. Although palliative care is very effective, physicians, nurses, patients, families, and loved ones regularly face clinically, ethically, legally, and morally challenging decisions throughout the dying process. This is especially true when terminally ill patients are ready to die in the face of complex, difficult-to-treat suffering and request assistance from their health care providers. Although physician-assisted suicide has received the most attention as a potential last-resort response, this practice remains illegal in the United States except in Oregon, and even there it is relatively infrequent. More commonly, decisions are made about accelerating opioid therapy for pain, foregoing life-sustaining therapy, voluntarily stopping eating and drinking, and administering terminal sedation in response to unacceptable suffering. The moral distinctions between these practices are critical to some but relatively inconsequential to others. This paper illustrates, through summaries of real clinical cases, how each of these practices might be used in response to patients in particular clinical circumstances, keeping in focus the patient's values as well as those of families, other loved ones, and health care providers. The challenge is to find the least harmful solution to the patient's problem without abandoning patients and their loved ones to unacceptable suffering or to acting in a more deleterious way on their own.

Responding to intractable terminal suffering: the role of terminal sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.

When provided by a skilled, multidisciplinary team, palliative care is highly effective at addressing the physical, psychological, social, and spiritual needs of dying patients and their families. However, some patients who have witnessed harsh death want reassurance that they can escape if their suffering becomes intolerable. In addition, a small percentage of terminally ill patients receiving comprehensive care reach a point at which their suffering becomes severe and unacceptable despite unrestrained palliative efforts; some of these patients request that death be hastened. This paper presents terminal sedation and voluntary refusal of hydration and nutrition as potential last resorts that can be used to address the needs of such patients. These two practices allow clinicians to address a much wider range of intractable end-of-life suffering than physician-assisted suicide (even if it were legal) and can also provide alternatives for patients, families, and clinicians who are morally opposed to physician-assisted suicide. This paper will define the two practices, distinguish them from more standard palliative care interventions and from physician-assisted suicide, illustrate them with a real clinical scenario, provide potential guidelines and practicalities, and explore their moral and legal status. Although medicine cannot sanitize dying or provide perfect answers for all challenging end-of-life clinical problems, terminal sedation and voluntary refusal of hydration and nutrition substantially increase patients' choices at this inherently challenging time.

Preparing the ground: contributions of the preclinical years to medical education for care near the end of life. Working Group on the Pre-clinical Years of the National Consensus Conference on Medical Education for Care Near the End of Life.

The preclinical years of medical education have rich potential for preparing medical students to provide optimal end-of-life care. Most of the opportunities and settings for this education already exist in the curricula of most medical schools, although they are underutilized for this purpose. In this report The Working Group on the Pre-clinical Years of the National Consensus Conference on Medical Education for Care Near the End of Life identifies the most promising settings and suggests how they might be used for maximum benefit in end-of-life education. Basic end-of-life care competencies are in five domains: (1) psychological, sociologic, cultural, and spiritual issues; (2) interviewing and communication skills; (3) management of common symptoms; (4) ethical issues; and (5) self-knowledge and self-reflection. A centralized group should oversee educational activities related to end-of-life care at each medical school. This group would identify and facilitate teaching opportunities in the preclinical curriculum: basic science courses; problem-based learning seminars; courses in interviewing, the doctor-patient relationship, and introduction to clinical medicine; courses in ethics, humanities, and the social-behavioral sciences; clinical preceptorships; and longitudinal experiences with patients. The group would also assess the potential impact of the "hidden curriculum."

A consensus-based approach to providing palliative care to patients who lack decision-making capacity. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.

Making palliative care decisions for a patient who lacks decision-making capacity presents several challenges. Other people, such as family and caregivers, must choose for the patient. The goals and values of these decision makers may conflict with those of each other and with those of the patient, who now lacks the capacity to participate in the decision. This paper presents a case study of a patient with severe Alzheimer disease who has two common clinical problems: neurogenic dysphagia and aspiration pneumonia. The case study describes a consensus-based decision-making strategy that keeps what is known about the patient's wishes and values in the foreground but also expects guidance from the physician and elicits input from family members and other people who care for and have knowledge about the patient. The steps of this process, including key clinical prompts and potential transition statements, are outlined and described. The overall goal of the case commentary is to demonstrate that physicians can guide a highly emotional and personal process in a structured manner that has meaning for the patient, family, physician, and other caregivers.

Somatization reconsidered: incorporating the patient's experience of illness.

The large and heterogeneous group of patients with "unexplained somatic symptoms," with or without coexisting psychiatric, "functional," or "organic" illnesses, provides continuing difficulty for clinicians. The construct of somatization artificially separates bodily and psychological symptoms that patients experience as a unified whole. Concurrent chronic illnesses make it difficult to exclude "general medical conditions." The diagnosis requires that the patient seek medical care. Conflict between patients' experiences of illness and physicians' diagnostic categories, and fear of blaming the patient, complicate naming and characterizing the illness. We recommend an approach to clinical care that involves exploring the patient's life context, finding mutually meaningful language to arrive at a name for the illness, normalizing the patient's bodily experience of distress, using a chronic disease model that attends to functioning, and addressing the physician's need for certainty and efficacy. Health systems can help coordinate care and avoid iatrogenic harm by appropriately controlling access to medical services.

A national survey of physician-assisted suicide and euthanasia in the United States.

BACKGROUND: Although there have been many studies of physician-assisted suicide and euthanasia in the United States, national data are lacking. METHODS: In 1996, we mailed questionnaires to a stratified probability sample of 3102 physicians in the 10 specialties in which doctors are most likely to receive requests from patients for assistance with suicide or euthanasia. We weighted the results to obtain nationally representative data. RESULTS: We received 1902 completed questionnaires (response rate, 61 percent). Eleven percent of the physicians said that under current legal constraints, there were circumstances in which they would be willing to hasten a patient's death by prescribing medication, and 7 percent said that they would provide a lethal injection; 36 percent and 24 percent, respectively, said that they would do so if it were legal. Since entering practice, 18.3 percent of the physicians (unweighted number, 320) reported having received a request from a patient for assistance with suicide and 11.1 percent (unweighted number, 196) had received a request for a lethal injection. Sixteen percent of the physicians receiving such requests (unweighted number, 42), or 3.3 percent of the entire sample, reported that they had written at least one prescription to be used to hasten death, and 4.7 percent (unweighted number, 59), said that they had administered at least one lethal injection. CONCLUSIONS: A substantial proportion of physicians in the United States report that they receive requests for physician-assisted suicide and euthanasia, and about 7 percent of those who responded to our survey have complied with such requests at least once.

Palliative options of last resort: a comparison of voluntarily stopping eating and drinking, terminal sedation, physician-assisted suicide, and voluntary active euthanasia.

Palliative care is generally agreed to be the standard of care for the dying, but there remain some patients for whom intolerable suffering persists. In the face of ethical and legal controversy about the acceptability of physician-assisted suicide and voluntary active euthanasia, voluntarily stopping eating and drinking and terminal sedation have been proposed as ethically superior responses of last resort that do not require changes in professional standards or the law. The clinical and ethical differences and similarities between these 4 practices are critically compared in light of the doctrine of double effect, the active/passive distinction, patient voluntariness, proportionality between risks and benefits, and the physician's potential conflict of duties. Terminal sedation and voluntarily stopping eating and drinking would allow clinicians to remain responsive to a wide range of patient suffering, but they are ethically and clinically more complex and closer to physician-assisted suicide and voluntary active euthanasia than is ordinarily acknowledged. Safeguards are presented for any medical action that may hasten death, including determining that palliative care is ineffective, obtaining informed consent, ensuring diagnostic and prognostic clarity, obtaining an independent second opinion, and implementing reporting and monitoring processes. Explicit public policy about which of these practices are permissible would reassure the many patients who fear a bad death in their future and allow for a predictable response for the few whose suffering becomes intolerable in spite of optimal palliative care.