The current coronavirus disease 2019 (COVID-19) pandemic has put significant strain on all aspects of health care delivery, including palliative care services. Given the high mortality from this ...disease, particularly in the more vulnerable members of society, it is important to examine how best to deliver a high standard of end-of-life care during this crisis. This case series collected data from two acute hospitals examining the management of patients diagnosed with COVID-19 who subsequently died (n = 36) and compared this with national and local end-of-life audit data for all other deaths. Our results demonstrated a shorter dying phase (38.25 hours vs. 74 hours) and higher rates of syringe driver use (72% vs. 33% in local audits), although with similar average mediation doses. Of note was the significant heterogeneity in the phenotype of deterioration in the dying phase, two distinct patterns emerged, with one group demonstrating severe illness with a short interval between symptom onset and death and another group presenting with a more protracted deterioration. This brief report suggests a spectrum of mode of dying. Overall, the cohort reflects previously described experiences, with increased frailty (median Clinical Frailty Scale score of 5) and extensive comorbidity burden. This brief report provides clinicians with a contemporaneous overview of our experience, knowledge, and pattern recognition when caring for people with COVID-19 and highlights the value of proactive identification of patients and risk of deterioration and palliation.
A magnetic, metallic inverse opal fabricated by infiltration into a silica nanosphere template assembled from spheres with diameters less than 100 nm is an archetypal example of a “metalattice”. In ...traditional quantum confined structures such as dots, wires, and thin films, the physical dynamics in the free dimensions is typically largely decoupled from the behavior in the confining directions. In a metalattice, the confined and extended degrees of freedom cannot be separated. Modeling predicts that magnetic metalattices should exhibit multiple topologically distinct magnetic phases separated by sharp transitions in their hysteresis curves as their spatial dimensions become comparable to and smaller than the magnetic exchange length, potentially enabling an interesting class of “spin-engineered” magnetic materials. The challenge to synthesizing magnetic inverse opal metalattices from templates assembled from sub-100 nm spheres is in infiltrating the nanoscale, tortuous voids between the nanospheres void-free with a suitable magnetic material. Chemical fluid deposition from supercritical carbon dioxide could be a viable approach to void-free infiltration of magnetic metals in view of the ability of supercritical fluids to penetrate small void spaces. However, we find that conventional chemical fluid deposition of the magnetic late transition metal nickel into sub-100 nm silica sphere templates in conventional macroscale reactors produces a film on top of the template that appears to largely block infiltration. Other deposition approaches also face difficulties in void-free infiltration into such small nanoscale templates or require conducting substrates that may interfere with properties measurements. Here we report that introduction of “spatial confinement” into the chemical fluid reactor allows for fabrication of nearly void-free nickel metalattices by infiltration into templates with sphere sizes from 14 to 100 nm. Magnetic measurements suggest that these nickel metalattices behave as interconnected systems rather than as isolated superparamagnetic systems coupled solely by dipolar interactions.
Background Sudden cardiac death (SCD) is a common cause of death in the United States. Few previous studies have investigated the associations of diet scores and dietary patterns with risk of SCD. We ...investigated the associations of the Mediterranean diet score and various dietary patterns with risk of SCD in participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study cohort. Methods and Results Diet was assessed with a food frequency questionnaire administered at baseline in REGARDS. The Mediterranean diet score was derived based on the consumption of specific food groups considered beneficial or detrimental components of that diet. Dietary patterns were derived previously using factor analysis, and adherence to each pattern was scored. SCD events were ascertained through regular contacts. Cox proportional hazards regression was used to examine the risk of SCD events associated with the Mediterranean diet score and adherence to each of the 5 dietary patterns overall and stratifying on history of coronary heart disease at baseline. The analytic sample included 21 069 participants with a mean 9.8±3.8 years of follow-up. The Mediterranean diet score showed a trend toward an inverse association with risk of SCD after multivariable adjustment (hazard ratio HR comparing highest with lowest group, 0.74; 95% CI, 0.55-1.01;
=0.07). There was a trend toward a positive association of the Southern dietary pattern with risk of SCD (HR comparing highest with lowest quartile of adherence, 1.46; 95% CI, 1.02-2.10;
=0.06). Conclusions In REGARDS participants, we identified trends toward an inverse association of the Mediterranean diet score and a positive association of adherence to the Southern dietary pattern with risk of SCD.
Abstract
Accurate assessment of tumor margins with specific, non-invasive imaging would result in the preservation of healthy tissue and improve long-term local tumor control, thereby reducing the ...risk of recurrence. Overexpression of epidermal growth factor receptor (EGFR) has been used in other cancers as an imaging biomarker to identify cancerous tissue. We hypothesize that expression of EGFR in ameloblastomas may be used to specifically visualize tumors. The aims of this study are to measure the specificity of radiolabeled
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Zr-panitumumab (an EGFR antibody) in vivo using patient-derived xenograft (PDX) models of ameloblastoma and positron emission tomography/computed tomography (PET/CT) scans. In PDX of ameloblastomas from four patients (AB-36, AB-37, AB-39 AB-53), the biodistribution of
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Zr-panitumumab was measured 120 h post-injection and was reported as the injected dose per gram of tissue (%ID/g; AB-36, 40%; AB-37, 62%; AB-39 18%; AB-53, 65%). The radiolabeled %ID/g was significantly greater in tumors of
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Zr-panitumumab-treated mice that did not receive unlabeled panitumumab as a blocking control for AB-36, AB-37, and AB-53. Radiolabeled anti-EGFR demonstrates specificity for ameloblastoma PDX tumor xenografts, we believe
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Zr-panitumumab is an attractive target for pre-surgical imaging of ameloblastomas. With this technology, we could more accurately assess tumor margins for the surgical removal of ameloblastomas.
The Simple View of Reading states that reading comprehension is the product of word recognition and listening comprehension. Whereas much research has focused on word recognition accuracy, recent ...attention has been directed toward word recognition fluency. The current study investigated whether a separate fluency component should be added to the Simple View of Reading. A battery of reading and language measures was administered to 604 children in second, fourth, and eighth grades. Approximately half these children had language and/or nonverbal cognitive impairments in kindergarten, but weighting procedures were used to reduce the potential bias this sampling characteristic may have entailed. Structural equation modeling was used to determine whether fluency accounted for unique variance in reading comprehension after controlling for word recognition accuracy and listening comprehension. Individual profile analyses were conducted to determine the number of individual participants who had poor fluency in the spite of good word recognition accuracy and listening comprehension. Results showed that fluency did not account for unique variance in reading comprehension and that few individuals had problems in fluency separate from word recognition accuracy or listening comprehension. Thus, it does not appear that a separate fluency component should be added to the Simple View of Reading.
We performed massively parallel sequencing of paired tumor/normal samples from 203 multiple myeloma (MM) patients and identified significantly mutated genes and copy number alterations and discovered ...putative tumor suppressor genes by determining homozygous deletions and loss of heterozygosity. We observed frequent mutations in KRAS (particularly in previously treated patients), NRAS, BRAF, FAM46C, TP53, and DIS3 (particularly in nonhyperdiploid MM). Mutations were often present in subclonal populations, and multiple mutations within the same pathway (e.g., KRAS, NRAS, and BRAF) were observed in the same patient. In vitro modeling predicts only partial treatment efficacy of targeting subclonal mutations, and even growth promotion of nonmutated subclones in some cases. These results emphasize the importance of heterogeneity analysis for treatment decisions.
•Deep sequencing reveals significant genetic events in multiple myeloma•Intratumor genetic heterogeneity is common in multiple myeloma•Recurrent mutations can occur either early or late in the evolution of a tumor•Genetic heterogeneity in cancer may limit effectiveness of targeted therapy
By the end of 2018 Kangerlussuaq Glacier in southeast Greenland had retreated further inland than at any time in the past 80 years and its terminus was approaching a region of retrograde bed slope ...from where further rapid retreat would have been inevitable. Here we show that the retreat occurred because the glacier failed to advance during the winters of 2016/17 and 2017/18 owing to a weakened proglacial mélange. This mixture of sea ice and icebergs is normally rigid enough to inhibit calving in winter, but for 2 consecutive years it repeatedly collapsed, allowing Kangerlussuaq Glacier to continue to calve all year round. The mélange break-ups followed the establishment of anomalously warm surface water on the continental shelf during 2016, which likely penetrated the fjord. As calving continued uninterrupted from summer 2016 to the end of 2018 the glacier accelerated by 35 % and thinned by 35 m. These observations demonstrate the importance of near-surface ocean temperatures in tidewater glacier stability and show that it is not only deep-ocean warming that can lead to glacier retreat. During winter 2019 a persistent mélange reformed and the glacier readvanced by 3.5 km.
Acute exercise suppresses ad libitum energy intake, but little is known about the effects of exercise on food reward brain regions. After an overnight fast, 30 (17 men, 13 women), healthy, habitually ...active (age = 22.2 ± 0.7 yr, body mass index = 23.6 ± 0.4 kg/m(2), Vo(2peak) = 44.2 ± 1.5 ml·kg(-1)·min(-1)) individuals completed 60 min of exercise on a cycle ergometer or 60 min of rest (no-exercise) in a counterbalanced, crossover fashion. After each condition, blood oxygen level-dependent responses to high-energy food, low-energy food, and control visual cues, were measured by functional magnetic resonance imaging. Exercise, compared with no-exercise, significantly (P < 0.005) reduced the neuronal response to food (high and low food) cues vs. control cues in the insula (-0.37 ± 0.13 vs. +0.07 ± 0.18%), putamen (-0.39 ± 0.10 vs. -0.10 ± 0.09%), and rolandic operculum (-0.37 ± 0.17 vs. 0.17 ± 0.12%). Exercise alone significantly (P < 0.005) reduced the neuronal response to high food vs. control and low food vs. control cues in the inferior orbitofrontal cortex (-0.94 ± 0.33%), insula (-0.37 ± 0.13%), and putamen (-0.41 ± 0.10%). No-exercise alone significantly (P < 0.005) reduced the neuronal response to high vs. control and low vs. control cues in the middle (-0.47 ± 0.15%) and inferior occipital gyrus (-1.00 ± 0.23%). Exercise reduced neuronal responses in brain regions consistent with reduced pleasure of food, reduced incentive motivation to eat, and reduced anticipation and consumption of food. Reduced neuronal response in these food reward brain regions after exercise is in line with the paradigm that acute exercise suppresses subsequent energy intake.
In ophthalmology, the designation of trachoma, onchocerciasis and leprosy as neglected tropical diseases (NTDs) has sustained efforts to combat these blinding conditions worldwide. Over the past 50 ...years, NTD designations have enabled the joining of political, social and economic forces to promote research and interventions for diseases that overwhelmingly affect the 3 billion people who subsist on less than 2 United States dollars (US$) a day. The global public health landscape is still dominated by focus on human immunodeficiency virus (HIV), tuberculosis and malaria. However, NTDs are now increasingly recognized as important causes of morbidity and mortality in low-income settings, perpetuating stigma and social isolation, with many NTDs leading to disfiguring complications. In international public health diplomacy, formal disease recognition is essential. The pursuit of this recognition drives proposals from World Health Organization’s (WHO’s) Member States to include additional diseases in the list of NTDs. The intention is to strengthen the development of partnerships, epidemiological frameworks and commitment of resources to achieve the aims set by the sustainable development goals
Altered resting state functional connectivity (FC) involving the anterior insula (aINS), a key node in the salience network, has been reported consistently in autism. Here we examined, for the first ...time, FC between the aINS and the whole brain in a sample of full-term, postmenstrual age (PMA) matched neonates (mean 44.0 weeks, SD = 1.5) who due to family history have high likelihood (HL) for developing autism (n = 12) and in controls (n = 41) without family history of autism (low likelihood, LL). Behaviors associated with autism were evaluated between 12 and 18 months (M = 17.3 months, SD = 2.5) in a subsample (25/53) of participants using the First Year Inventory (FYI). Compared to LL controls, HL neonates showed hypoconnectivity between left aINS and left amygdala. Lower connectivity between the two nodes was associated with higher FYI risk scores in the social domain (r(25) = -0.561, p = .003) and this association remained robust when maternal mental health factors were considered. Considering that a subsample of LL participants (n = 14/41) underwent brain imaging during the fetal period at PMA 31 and 34 weeks, in an exploratory analysis, we evaluated prospectively development of the LaINS-Lamy connectivity and found that the two areas strongly coactivate throughout the third trimester of pregnancy. The study identifies left lateralized anterior insula-amygdala connectivity as a potential target of further investigation into neural circuitry that enhances likelihood of future onset of social behaviors associated with autism during neonatal and potentially prenatal periods.
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