Patagonian dust, Agulhas Current, and Antarctic ice-rafted debris contributions to the South Atlantic Ocean over the past 150,000 years.

Disentangling inputs of aeolian dust, ice-rafted debris (IRD), and eroded continental detritus delivered by ocean currents to marine sediments provide important insights into Earth System processes and climate. This study uses Sr-Nd-Pb isotope ratios of the continent-derived (lithogenic) fraction in deep-sea core TN057-6 from the subantarctic Southern Ocean southwest of Africa over the past 150,000 y to identify source regions and quantify their relative contributions and fluxes utilizing a mixing model set in a Bayesian framework. The data are compared with proxies from parallel core Ocean Drilling Program Site 1090 and newly presented data from potential South America aeolian dust source areas (PSAs), allowing for an integrated investigation into atmospheric, oceanic, and cryospheric dynamics. PSA inputs varied on glacial/interglacial timescales, with southern South American sources dominating up to 88% of the lithogenic fraction (mainly Patagonia, which provided up to 68%) during cold periods, while southern African sources were more important during interglacials. During the warmer Marine Isotope Stage (MIS) 3 of the last glacial period, lithogenic fluxes were twice that of colder MIS2 and MIS4 at times, and showed unique isotope ratios best explained by Antarctic-derived IRD, likely from the Weddell Sea. The IRD intrusions contributed up to 41% at times and followed Antarctic millennial warming events that raised temperatures, causing instability of icesheet margins. High IRD was synchronous with increased bioavailable iron, nutrient utilization, high biological productivity, and decreased atmospheric CO2. Overall, TN057-6 sediments record systematic Southern Hemisphere climate shifts and cryospheric changes that impacted biogeochemical cycling on both glacial/interglacial and subglacial timescales.

Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment.

Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

Structured interdisciplinary bedside rounds improve interprofessional communication and workplace efficiency among residents and nurses on an inpatient internal medicine unit.

Structured Interdisciplinary Bedside Rounds (SIBR) is a standardized, team-based intervention for hospitals to deliver high quality interprofessional care. Despite its potential for improving IPC and the workplace environment, relatively little is known about SIBR's effect on these outcomes. Our study aimed to assess the fidelity of SIBR implementation on an inpatient medicine teaching unit and its effects on perceived IPC and workplace efficiency. We conducted a quasi-experimental study with 88 residents and 44 nurses at a large academic medical center and observed 1308 SIBR encounters over 24 weeks. Of these 1308 encounters, the bedside nurse was present for 96.7%, physician for 97.6%, and care manager for 94.7, and 64.7% occurred at the bedside. Following SIBR implementation, perceived IPC improved significantly among residents (93.3% versus 67.9%, p < .024) and nurses (73.7% versus 36.0%, p < .008) compared to before implementation. Moreover, residents perceived greater workplace efficiency operationalized as being paged less frequently with questions by nurses (20.0% versus 49.1%, p = .01). No statistically significant improvements were reported regarding burnout, meaning at work, and workplace satisfaction. Our implementation of SIBR significantly improved perceived IPC and workplace efficiency, which are two important domains of healthcare quality. Future work should examine the impact of SIBR on patient-centered outcomes such as patient experience.

Post-discharge neonatal hyperbilirubinemia surveillance.

AIM: To assess implementation of the Israel Neonatal Society's 2008 guidelines for universal community assessment of jaundice within 72 hours of discharge from birth hospitalisation. METHODS: Mothers of newborns were interviewed at Maternal Child Health Clinics in the Jerusalem District, Israel, and asked whether their newborn had been evaluated for jaundice within the recommended time frame. Newborn discharge letters from Israeli hospitals were assessed for appropriate inclusion of instructions for early follow-up for jaundice. RESULTS: Out of 659, 217 (32.9%) mothers whose newborns were at low risk for neonatal hyperbilirubinemia reported an examination within 72 hours of discharge. Eighteen (8.3%) were referred for a bilirubin test. In contrast, 99.1% (109/110) of high-risk newborns who were specifically invited for a bilirubin test the day following discharge complied. Out of 26, 12 (46.2%) hospital discharge letters specified both a time limit of 72 hours post-discharge and jaundice as a reason for early follow-up. CONCLUSION: The early community surveillance rate for jaundice was low, contrasting with near universal compliance in those who received a specific instruction for a post-discharge bilirubin blood test. Inclusion of specific written instructions in hospital discharge summaries was also low and may contribute to poor implementation of guidelines.

Cloud Computing for COVID-19: Lessons Learned From Massively Parallel Models of Ventilator Splitting.

A patient-specific airflow simulation was developed to help address the pressing need for an expansion of the ventilator capacity in response to the COVID-19 pandemic. The computational model provides guidance regarding how to split a ventilator between two or more patients with differing respiratory physiologies. To address the need for fast deployment and identification of optimal patient-specific tuning, there was a need to simulate hundreds of millions of different clinically relevant parameter combinations in a short time. This task, driven by the dire circumstances, presented unique computational and research challenges. We present here the guiding principles and lessons learned as to how a large-scale and robust cloud instance was designed and deployed within 24 hours and 800 000 compute hours were utilized in a 72-hour period. We discuss the design choices to enable a quick turnaround of the model, execute the simulation, and create an intuitive and interactive interface.

Effect of omalizumab on outcomes in patients with aspirin-exacerbated respiratory disease.

Background: The current treatment for patients with aspirin-exacerbated respiratory disease (AERD) who have uncontrolled asthma or chronic rhinosinusitis is aspirin desensitization. For patients who are unable to undergo or do not benefit from aspirin desensitization, treatment with biologics is an option, although efficacy data for AERD is scarce. Objective: We reported a series of patients with AERD who were started on omalizumab and measured the outcomes to assess improvement. Methods: Adult patients with AERD who were initiated on omalizumab from January 2007 to January 2018 were included. We compared outcomes 6-12 months before initiating biologic therapy and during the last 6-12 months while they were on biologic therapy. Our study investigated the number of oral steroid courses, short-acting beta-agonists (SABA), antibiotics for sinusitis or pneumonia, emergency department visits, hospitalizations, pulmonary function tests, and changes in controller medications. Results: Twenty-nine patients were placed on omalizumab. Sixty-two percent demonstrated a reduction in the number of steroid courses (p = 0.0014) and number of SABA canisters used (p = 0.0005) during their last 12 months while on omalizumab. Eighty-six percent of the patients with AERD and on omalizumab demonstrated either a decrease in the number of steroid courses or number of SABA canisters used in the last year of the study. The patients with AERD and with concomitant immunoglobulin E (IgE) mediated respiratory disease showed a statistically significant reduction in the number of steroid courses and number of SABA canisters used while on omalizumab for 1 year (p = 0.002 and p = 0.005, respectively), whereas those without concomitant IgE-mediated respiratory disease did not have a substantial reduction in steroids or SABA canisters used. Conclusion: Our case series reported that omalizumab could effectively be used as an adjunct treatment for AERD, but additional larger and longitudinal studies are needed to corroborate these findings.

Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy?

BACKGROUND: Neonatal asphyxia is often associated with hepatic injury. We hypothesized that this might lead to increased bilirubin concentrations. STUDY DESIGN: Term neonates admitted between January 2015 and April 2017 who remained hospitalized for ≥ 4 days and who had serial serum bilirubin concentrations recorded were divided into those with neonatal encephalopathy (NE) and controls. Serial serum bilirubin concentrations during the first days of life were compared between groups. RESULTS: Twenty-nine neonates with NE and 84 age-matched controls were identified. Mean total serum bilirubin concentrations of NE babies were significantly lower than those controls throughout the first days of life. At 96 hours of age, NE serum bilirubin concentrations were 4.5 (3.2, 5.8) versus controls of 10.5 (9.4, 11.5) mg/dL (p < 0.0001). The mean area under the curve (AUC) for the NE group was 268 (215, 321) versus 663 (608, 718), p < 0.0001, for the control group. All of the NE babies remained below the 40th percentile of the Bhutani curve and none required phototherapy. CONCLUSION: Contrary to our hypothesis, bilirubin concentrations in NE infants are significantly lower than expected during the first 4 days postnatally. We speculate that, under conditions of severe oxidative stress, bilirubin is consumed as an antioxidant.

Anaphylaxis in a health maintenance organization: International Classification of Diseases coding and epinephrine auto-injector prescribing.

BACKGROUND: Accurate estimates of the incidence of anaphylaxis are limited. Current International Classification of Diseases, Ninth Revision (ICD-9) codes complicate accurate diagnosis of anaphylaxis and assessment of appropriate epinephrine prescribing. OBJECTIVE: To quantify the incidence and demographic character of patients with anaphylaxis-related ICD-9 codes in a large health maintenance organization and analyze epinephrine prescribing and dispensing rates. METHODS: All patients included had at least 12 months of continuous membership over a 4-year period from January 1, 2008 to December 31, 2012 and were selected based on anaphylaxis-related ICD-9 codes (N = 159,172). This algorithm was extrapolated from a previous study that used expanded ICD-9 codes to identify more cases of anaphylaxis. Individual chart reviews found that many expanded ICD-9 codes represented unconfirmed cases of anaphylaxis and therefore were excluded, resulting in analysis of 52,405 patients. RESULTS: Incidence of anaphylaxis over 4 years was 2.07%, with female predominance (56.5%) over male predominance (43.5%). Epinephrine was prescribed in 16.2% of total cases. Highest rates of epinephrine prescription were for traditional ICD-9 codes 995.0 (other anaphylactic shock) and 995.60 to 995.69 (anaphylactic shock caused by food) at 49.3% and 58.6%, respectively. Of the cases in which an epinephrine auto-injector was prescribed, it was dispensed 95.9% of the time, independent of copayment amount. CONCLUSION: Low epinephrine auto-injector prescribing rates in cases of anaphylaxis suggest the continued difficulty in the diagnosis of anaphylaxis and could result in suboptimal treatment of potential future episodes.

Venous Intervention Improves Patient Outcomes.

INTRODUCTION: The healing of venous ulcers is difficult, and several sources indicate a multidisciplinary plan of care as the best approach to the healing of these wounds. MATERIALS AND METHODS: Seventy-five patients with suspected venous disease being treated at Northern New Jersey Medical Center were assessed by dedicated interventional radiology physicians as part of Wound Center protocol. Of those patients, 27 required diagnostic testing, such as CT venogram or venography. Of these patients, 11 were determined to be appropriate candidates and underwent surgical intervention, such as venous ablation or vein stenting. RESULTS: Results support continued referral for venous interventions. Of the 75 patients referred for assessment, 27 required diagnostic testing, and 11 of those patients met criteria for intervention and treatment. Of the 11 patients who underwent surgical intervention, 100% experienced success in reduction of one or more cardinal signs of inflammation, and all patients with open wounds experienced either reduction in wound size and, more commonly, complete wound closure. CONCLUSION: Adding venous evaluation referral to wound center protocol in patients with suspected venous disease improved healing outcomes, thus improving quality of life.

Glacier retreat in New Zealand during the Younger Dryas stadial.

Millennial-scale cold reversals in the high latitudes of both hemispheres interrupted the last transition from full glacial to interglacial climate conditions. The presence of the Younger Dryas stadial (approximately 12.9 to approximately 11.7 kyr ago) is established throughout much of the Northern Hemisphere, but the global timing, nature and extent of the event are not well established. Evidence in mid to low latitudes of the Southern Hemisphere, in particular, has remained perplexing. The debate has in part focused on the behaviour of mountain glaciers in New Zealand, where previous research has found equivocal evidence for the precise timing of increased or reduced ice extent. The interhemispheric behaviour of the climate system during the Younger Dryas thus remains an open question, fundamentally limiting our ability to formulate realistic models of global climate dynamics for this time period. Here we show that New Zealand's glaciers retreated after approximately 13 kyr bp, at the onset of the Younger Dryas, and in general over the subsequent approximately 1.5-kyr period. Our evidence is based on detailed landform mapping, a high-precision (10)Be chronology and reconstruction of former ice extents and snow lines from well-preserved cirque moraines. Our late-glacial glacier chronology matches climatic trends in Antarctica, Southern Ocean behaviour and variations in atmospheric CO(2). The evidence points to a distinct warming of the southern mid-latitude atmosphere during the Younger Dryas and a close coupling between New Zealand's cryosphere and southern high-latitude climate. These findings support the hypothesis that extensive winter sea ice and curtailed meridional ocean overturning in the North Atlantic led to a strong interhemispheric thermal gradient during late-glacial times, in turn leading to increased upwelling and CO(2) release from the Southern Ocean, thereby triggering Southern Hemisphere warming during the northern Younger Dryas.

Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271.

The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.

Rhs proteins from diverse bacteria mediate intercellular competition.

Rearrangement hotspot (Rhs) and related YD-peptide repeat proteins are widely distributed in bacteria and eukaryotes, but their functions are poorly understood. Here, we show that Gram-negative Rhs proteins and the distantly related wall-associated protein A (WapA) from Gram-positive bacteria mediate intercellular competition. Rhs and WapA carry polymorphic C-terminal toxin domains (Rhs-CT/WapA-CT), which are deployed to inhibit the growth of neighboring cells. These systems also encode sequence-diverse immunity proteins (RhsI/WapI) that specifically neutralize cognate toxins to protect rhs(+)/wapA(+) cells from autoinhibition. RhsA and RhsB from Dickeya dadantii 3937 carry nuclease domains that degrade target cell DNA. D. dadantii 3937 rhs genes do not encode secretion signal sequences but are linked to hemolysin-coregulated protein and valine-glycine repeat protein G genes from type VI secretion systems. Valine-glycine repeat protein G is required for inhibitor cell function, suggesting that Rhs may be exported from D. dadantii 3937 through a type VI secretion mechanism. In contrast, WapA proteins from Bacillus subtilis strains appear to be exported through the general secretory pathway and deliver a variety of tRNase toxins into neighboring target cells. These findings demonstrate that YD-repeat proteins from phylogenetically diverse bacteria share a common function in contact-dependent growth inhibition.

Glucose-6-Phosphate Dehydrogenase Screening in Israel-Arab and Palestinian-Arab Neonates.

OBJECTIVE: To evaluate the frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, the incidence of clinically significant jaundice (any serum total bilirubin value >75th percentile on the hour-specific bilirubin nomogram), and the need for phototherapy in the pooled male Israeli-Arab and Palestinian-Arab population born at the Shaare Zedek Medical Center in Jerusalem, Israel. STUDY DESIGN: Quantitative G-6-PD enzyme testing of umbilical cord blood was performed during birth hospitalization. G-6-PD deficiency was defined as any G-6-PD value <7.0 U/gHb. Transcutaneous bilirubin was performed daily during birth hospitalization, with serum total bilirubin testing in those with a transcutaneous bilirubin value >75th percentile. RESULTS: Ten of 286 (3.5%) consecutively delivered male Arab newborns had G-6-PD deficiency. Clinically significant jaundice was higher in the population with G-6-PD deficiency compared with normal controls (relative risk, 3.45; 95% CI, 1.24-9.58). Thirty percent of the newborns with G-6-PD deficiency met American Academy of Pediatrics indications for phototherapy according to the high-risk (middle) curve on the phototherapy graph. CONCLUSION: The frequency of G-6-PD deficiency in the Arab neonatal population delivering at this medical center meets World Health Organization criteria for neonatal G-6-PD screening (3%-5%). As in other ethnic groups, clinically significant jaundice is more frequent in newborns of this ethnic group with G-6-PD deficiency compared with G-6-PD-normal controls. Neonatal G-6-PD screening for both males and females of this population subgroup, in conjunction with parental education regarding the dangers of the condition and its prophylaxis, has now been incorporated into our institution's routine G-6-PD screening program.

Association of reactive oxygen species levels and radioresistance in cancer stem cells.

The metabolism of oxygen, although central to life, produces reactive oxygen species (ROS) that have been implicated in processes as diverse as cancer, cardiovascular disease and ageing. It has recently been shown that central nervous system stem cells and haematopoietic stem cells and early progenitors contain lower levels of ROS than their more mature progeny, and that these differences are critical for maintaining stem cell function. We proposed that epithelial tissue stem cells and their cancer stem cell (CSC) counterparts may also share this property. Here we show that normal mammary epithelial stem cells contain lower concentrations of ROS than their more mature progeny cells. Notably, subsets of CSCs in some human and murine breast tumours contain lower ROS levels than corresponding non-tumorigenic cells (NTCs). Consistent with ROS being critical mediators of ionizing-radiation-induced cell killing, CSCs in these tumours develop less DNA damage and are preferentially spared after irradiation compared to NTCs. Lower ROS levels in CSCs are associated with increased expression of free radical scavenging systems. Pharmacological depletion of ROS scavengers in CSCs markedly decreases their clonogenicity and results in radiosensitization. These results indicate that, similar to normal tissue stem cells, subsets of CSCs in some tumours contain lower ROS levels and enhanced ROS defences compared to their non-tumorigenic progeny, which may contribute to tumour radioresistance.

Cholinergic urticaria with anaphylaxis: hazardous duty of a deployed US marine.

Cholinergic urticaria (CU) is triggered by a rise in body temperature and can be complicated by bronchial hyperresponsiveness and anaphylaxis. It primarily affects young adults who actively engage in strenuous exercise, such as servicemen and servicewomen. If the patient reports a history of wheezing or difficulty breathing with urticaria, a water challenge test in a warm bath can be performed to confirm the presence of anaphylaxis. The test should be conducted in an environment in which the patient's airway can be secured and epinephrine can be administered if necessary. Nonsedating antihistamines commonly are used to treat CU, but few other treatments have been thoroughly evaluated for cases that are refractory to antihistamines. We present the case of a 27-year-old US Marine with CU and anaphylaxis confirmed by a water challenge test in a warm bath.