Robert Morrison

Bio: Robert Morrison is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Malaria & Plasmodium falciparum. The author has an hindex of 7, co-authored 12 publications receiving 537 citations. Previous affiliations of Robert Morrison include Seattle Biomed.

Self-reported symptom experience of critically ill cancer patients receiving intensive care.

Abstract: Objective To characterize the symptom experience of a cohort of intensive care unit (ICU) patients at high risk for hospital death. Design Prospective analysis of patients with a present or past diagnosis of cancer who were consecutively admitted to a medical ICU during an 8-month period. Setting Academic, university-affiliated, tertiary-care, urban medical center. Patients One hundred cancer patients treated in a medical ICU. Intervention Assessment of symptoms. Measurements Patients’ self-reports of symptoms using the Edmonton Symptom Assessment Scale (ESAS), and ratings of pain or discomfort associated with ICU diagnostic/therapeutic procedures and of stress associated with conditions in the ICU. Main Results Hospital mortality for the group was 56%. Fifty patients had the capacity to respond to the ESAS, among whom 100% provided symptom reports. Between 55% and 75% of ESAS responders reported experiencing pain, discomfort, anxiety, sleep disturbance, or unsatisfied hunger or thirst that they rated as moderate or severe, whereas depression and dyspnea at these levels were reported by approximately 40% and 33% of responders, respectively. Significant pain, discomfort, or both were associated with common ICU procedures, but most procedure-related symptoms were controlled adequately for a majority of patients. Inability to communicate, sleep disruption, and limitations on visiting were particularly stressful among ICU conditions studied. Conclusions Among critically ill cancer patients, multiple distressing symptoms were common in the ICU, often at significant levels of severity. Symptom assessment may suggest more effective strategies for symptom control and may direct decisions about appropriate use of ICU therapies.

γδ T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations

Abstract: Whole-sporozoite vaccines confer sterilizing immunity to malaria-naive individuals by unknown mechanisms. In the first PfSPZ Vaccine trial ever in a malaria-endemic population, Vδ2 γδ T cells were significantly elevated and Vγ9/Vδ2 transcripts ranked as the most upregulated in vaccinees who were protected from Plasmodium falciparum infection. In a mouse model, absence of γδ T cells during vaccination impaired protective CD8 T cell responses and ablated sterile protection. γδ T cells were not required for circumsporozoite protein-specific Ab responses, and γδ T cell depletion before infectious challenge did not ablate protection. γδ T cells alone were insufficient to induce protection and required the presence of CD8α+ dendritic cells. In the absence of γδ T cells, CD8α+ dendritic cells did not accumulate in the livers of vaccinated mice. Altogether, our results show that γδ T cells were essential for the induction of sterile immunity during whole-organism vaccination.

VAR2CSA Domain-Specific Analysis of Naturally Acquired Functional Antibodies to Plasmodium falciparum Placental Malaria

Abstract: Background Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) that surface-express VAR2CSA and bind chondroitin sulfate A The inflammatory response to placenta-sequestered parasites is associated with poor pregnancy outcomes, and protection may be mediated in part by VAR2CSA antibodies that block placental IE adhesion Methods In this study, we used a new approach to assess VAR2CSA domains for functional epitopes recognized by naturally acquired antibodies Antigen-specific immunoglobulin (Ig) G targeting Duffy binding-like (DBL) domains from different alleles were sequentially purified from plasma pooled from multigravid women and then characterized using enzyme-linked immunosorbent assay, flow cytometry, and antiadhesion assays Results Different DBL domain-specific IgGs could react to homologous as well as heterologous antigens and parasites, suggesting that conserved epitopes are shared between allelic variants Homologous blocking of IE binding was observed with ID1-DBL2-ID2a-, DBL4-, and DBL5-specific IgG (range, 42%-75%), whereas partial cross-inhibition activity was observed with purified IgG specific to ID1-DBL2-ID2a and DBL4 antigens Plasma retained broadly neutralizing activity after complete depletion of these VAR2CSA specificities Conclusions Broadly neutralizing antibodies of multigravidae are not depleted on VAR2CSA recombinant antigens, and hence development of VAR2CSA vaccines based on a single construct and variant might induce antibodies with limited broadly neutralizing activity

Maternal Microchimerism Predicts Increased Infection but Decreased Disease due to Plasmodium falciparum During Early Childhood.

Abstract: Background A mother's infection with placental malaria (PM) can affect her child's susceptibility to malaria, although the mechanism remains unclear The fetus acquires a small amount of maternal cells and DNA known as maternal microchimerism (MMc), and we hypothesized that PM increases MMc and that MMc alters risk of Plasmodium falciparum malaria during infancy Methods In a nested cohort from Muheza, Tanzania, we evaluated the presence and level of cord blood MMc in offspring of women with and without PM A maternal-specific polymorphism was identified for each maternal-infant pair, and MMc was assayed by quantitative polymerase chain reaction The ability of MMc to predict malaria outcomes during early childhood was evaluated in longitudinal models Results Inflammatory PM increased the detection rate of MMc among offspring of primigravidae and secundigravidae, and both noninflammatory and inflammatory PM increased the level of MMc Detectable MMc predicted increased risk of positive blood smear but, interestingly, decreased risk of symptomatic malaria and malaria hospitalization Conclusions The acquisition of MMc may result in increased malaria infection but protection from malaria disease Future studies should be directed at the cellular component of MMc, with attention to its ability to directly or indirectly coordinate anti-malarial immune responses in the offspring

Identification of Novel Pre-Erythrocytic Malaria Antigen Candidates for Combination Vaccines with Circumsporozoite Protein

Abstract: Malaria vaccine development has been hampered by the limited availability of antigens identified through conventional discovery approaches, and improvements are needed to enhance the efficacy of the leading vaccine candidate RTS,S that targets the circumsporozoite protein (CSP) of the infective sporozoite. Here we report a transcriptome-based approach to identify novel pre-erythrocytic vaccine antigens that could potentially be used in combination with CSP. We hypothesized that stage-specific upregulated genes would enrich for protective vaccine targets, and used tiling microarray to identify P. falciparum genes transcribed at higher levels during liver stage versus sporozoite or blood stages of development. We prepared DNA vaccines for 21 genes using the predicted orthologues in P. yoelii and P. berghei and tested their efficacy using different delivery methods against pre-erythrocytic malaria in rodent models. In our primary screen using P. yoelii in BALB/c mice, we found that 16 antigens significantly reduced liver stage parasite burden. In our confirmatory screen using P. berghei in C57Bl/6 mice, we confirmed 6 antigens that were protective in both models. Two antigens, when combined with CSP, provided significantly greater protection than CSP alone in both models. Based on the observations reported here, transcriptional patterns of Plasmodium genes can be useful in identifying novel pre-erythrocytic antigens that induce protective immunity alone or in combination with CSP.

Recommendations for end-of-life care in the intensive care unit: A consensus statement by the American College of Critical Care Medicine

Abstract: Background: These recommendations have been developed to improve the care of intensive care unit (ICU) patients during the dying process. The recommendations build on those published in 2003 and highlight recent developments in the field from a U.S. perspective. They do not use an evidence grading system because most of the recommendations are based on ethical and legal principles that are not derived from empirically based evidence. Principal Findings: Family-centered care, which emphasizes the importance of the social structure within which patients are embedded, has emerged as a comprehensive ideal for managing end-of-life care in the ICU. ICU clinicians should be competent in all aspects of this care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment and the use of sedatives, analgesics, and nonpharmacologic approaches to easing the suffering of the dying process. Several key ethical concepts play a foundational role in guiding end-oflife care, including the distinctions between withholding and withdrawing treatments, between actions of killing and allowing to die, and between consequences that are intended vs. those that are merely foreseen (the doctrine of double effect). Improved communication with the family has been shown to improve patient care and family outcomes. Other knowledge unique to endof-life care includes principles for notifying families of a patient’s death and compassionate approaches to discussing options for organ donation. End-of-life care continues even after the death of the patient, and ICUs should consider developing comprehensive bereavement programs to support both families and the needs of the clinical staff. Finally, a comprehensive agenda for improving end-of-life care in the ICU has been developed to guide research, quality improvement efforts, and educational curricula. Conclusions: End-of-life care is emerging as a comprehensive area of expertise in the ICU and demands the same high level of knowledge and competence as all other areas of ICU practice. (Crit Care Med 2008; 36:953‐963)

Biomarkers of Nutrition for Development (BOND)-Iron Review.

Abstract: The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-based advice to anyone with an interest in the role of nutrition in health. Specifically, the BOND program provides state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutrients in body tissues at the individual and population level. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, iron, zinc, folate, vitamin A, and vitamin B-12. This review represents the second in the series of reviews and covers all relevant aspects of folate biology and biomarkers. The article is organized to provide the reader with a full appreciation of folate's history as a public health issue, its biology, and an overview of available biomarkers (serum folate, RBC folate, and plasma homocysteine concentrations) and their interpretation across a range of clinical and population-based uses. The article also includes a list of priority research needs for advancing the area of folate biomarkers related to nutritional health status and development.

Nurse-physician perspectives on the care of dying patients in intensive care units: collaboration, moral distress, and ethical climate.

Abstract: Objective:To explore registered nurses’ and attending physicians’ perspectives on caring for dying patients in intensive care units (ICUs), with particular attention to the relationships among moral distress, ethical climate, physician/nurse collaboration, and satisfaction with quality of care.Desig

Place of Death: Correlations With Quality of Life of Patients With Cancer and Predictors of Bereaved Caregivers' Mental Health

Abstract: Purpose To determine whether the place of death for patients with cancer is associated with patients' quality of life (QoL) at the end of life (EOL) and psychiatric disorders in bereaved caregivers. Patients and Methods Prospective, longitudinal, multisite study of patients with advanced cancer and their caregivers (n = 342 dyads). Patients were followed from enrollment to death, a median of 4.5 months later. Patients' QoL at the EOL was assessed by caregiver report within 2 weeks of death. Bereaved caregivers' mental health was assessed at baseline and 6 months after loss with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the Prolonged Grief Disorder interview. Results In adjusted analyses, patients with cancer who died in an intensive care unit (ICU) or hospital experienced more physical and emotional distress and worse QoL at the EOL (all P ≤ .03), compared with patients who died at home with hospice. ICU deaths were associated with a h...