Oxide- and Silicate-Water Interfaces and Their Roles in Technology and the Environment.

Interfacial reactions drive all elemental cycling on Earth and play pivotal roles in human activities such as agriculture, water purification, energy production and storage, environmental contaminant remediation, and nuclear waste repository management. The onset of the 21st century marked the beginning of a more detailed understanding of mineral aqueous interfaces enabled by advances in techniques that use tunable high-flux focused ultrafast laser and X-ray sources to provide near-atomic measurement resolution, as well as by nanofabrication approaches that enable transmission electron microscopy in a liquid cell. This leap into atomic- and nanometer-scale measurements has uncovered scale-dependent phenomena whose reaction thermodynamics, kinetics, and pathways deviate from previous observations made on larger systems. A second key advance is new experimental evidence for what scientists hypothesized but could not test previously, namely, interfacial chemical reactions are frequently driven by "anomalies" or "non-idealities" such as defects, nanoconfinement, and other nontypical chemical structures. Third, progress in computational chemistry has yielded new insights that allow a move beyond simple schematics, leading to a molecular model of these complex interfaces. In combination with surface-sensitive measurements, we have gained knowledge of the interfacial structure and dynamics, including the underlying solid surface and the immediately adjacent water and aqueous ions, enabling a better definition of what constitutes the oxide- and silicate-water interfaces. This critical review discusses how science progresses from understanding ideal solid-water interfaces to more realistic systems, focusing on accomplishments in the last 20 years and identifying challenges and future opportunities for the community to address. We anticipate that the next 20 years will focus on understanding and predicting dynamic transient and reactive structures over greater spatial and temporal ranges as well as systems of greater structural and chemical complexity. Closer collaborations of theoretical and experimental experts across disciplines will continue to be critical to achieving this great aspiration.

Efficacy and Safety of Long-Acting Subcutaneous Lenacapavir in Heavily Treatment-Experienced People with Multi-Drug Resistant HIV-1: Week 104 Results of a Phase 2/3 Trial.

BACKGROUND: Lenacapavir is a long-acting HIV-1 capsid inhibitor for treatment of HIV-1 infection. We evaluated the efficacy and safety of lenacapavir in combination with an investigator-selected optimized background regimen (OBR) after 104 weeks in adults with multidrug-resistant HIV-1. METHODS: This ongoing, international, Phase 2/3 trial at 42 sites included 72 adults living with multidrug-resistant HIV-1. Following a 2-week oral lenacapavir loading phase, participants received subcutaneous lenacapavir every 26 weeks with an OBR. HIV-1 RNA, CD4 cell counts, and adverse events were assessed over 104 weeks. One participant did not enter the extension phase. RESULTS: At Week 104, 44 of 71 participants (62%, 95% CI 50; 73) had HIV-1 RNA <50 copies/mL via US Food & Drug Administration (FDA) snapshot algorithm. When missing data (including discontinuations) were excluded, 44 of 54 participants (82%) had HIV-1 RNA <50 copies/mL at Week 104, mean CD4 cell count increased by 122 cells/µL (95% CI 80; 165), and the proportion of participants with CD4 cell count <200 cells/µL decreased from 64% (46 of 72) at Baseline to 29% (16 of 55). Fourteen participants had treatment-emergent lenacapavir resistance; seven resuppressed (HIV-1 RNA <50 copies/mL) while maintaining lenacapavir use. There were no Grade 4 or serious treatment-related adverse events. One participant discontinued study drug due to an injection site reaction. CONCLUSIONS: Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks. Lenacapavir represents an important treatment option in people with multidrug-resistant HIV-1.

Chemical and Reactive Transport Processes Associated with Hydraulic Fracturing of Unconventional Oil/Gas Shales.

Hydraulic fracturing of unconventional oil/gas shales has changed the energy landscape of the U.S. Recovery of hydrocarbons from tight, hydraulically fractured shales is a highly inefficient process, with estimated recoveries of <25% for natural gas and <5% for oil. This review focuses on the complex chemical interactions of additives in hydraulic fracturing fluid (HFF) with minerals and organic matter in oil/gas shales. These interactions are intended to increase hydrocarbon recovery by increasing porosities and permeabilities of tight shales. However, fluid-shale interactions result in the dissolution of shale minerals and the release and transport of chemical components. They also result in mineral precipitation in the shale matrix, which can reduce permeability, porosity, and hydrocarbon recovery. Competition between mineral dissolution and mineral precipitation processes influences the amounts of oil and gas recovered. We review the temporal/spatial origins and distribution of unconventional oil/gas shales from mudstones and shales, followed by discussion of their global and U.S. distributions and compositional differences from different U.S. sedimentary basins. We discuss the major types of chemical additives in HFF with their intended purposes, including drilling muds. Fracture distribution, porosity, permeability, and the identity and molecular-level speciation of minerals and organic matter in oil/gas shales throughout the hydraulic fracturing process are discussed. Also discussed are analysis methods used in characterizing oil/gas shales before and after hydraulic fracturing, including permeametry and porosimetry measurements, X-ray diffraction/Rietveld refinement, X-ray computed tomography, scanning/transmission electron microscopy, and laboratory- and synchrotron-based imaging/spectroscopic methods. Reactive transport and spatial scaling are discussed in some detail in order to relate fundamental molecular-scale processes to fluid transport. Our review concludes with a discussion of potential environmental impacts of hydraulic fracturing and important knowledge gaps that must be bridged to achieve improved mechanistic understanding of fluid transport in oil/gas shales.

The effect of illumination on the visibility of steps and ramps for people with low vision.

SIGNIFICANCE: Poor visibility of indoor features such as steps and ramps can pose mobility hazards for people with low vision. For purposes of architectural design, it is important to understand how design parameters such as the illumination level of an indoor space affect the visibility of steps and ramps. PURPOSE: This study was aimed to examine the effect of typical variation in photopic illumination level in an indoor space on the visibility of steps and ramps for individuals with low vision. METHODS: Steps and ramps were constructed in a large windowless room illuminated by overhead lights. Subjects with low vision completed a 5-alternative forced choice task to recognize the targets at three levels of photopic illumination, i.e., 800, 80, and 8 lux, and gave confidence ratings about their judgments on a 5-point scale. Acuities and contrast sensitivities of the subjects were also measured at each illumination level. For comparison, a group of normally sighted subjects with simulated acuity reduction also completed the step-and-ramp recognition task. RESULTS: For both groups of subjects, recognition accuracy was not affected by illumination level. For subjects with low vision, however, there was a significant effect of illumination level on confidence rating: subjects became more confident about their judgments with increasing illumination. There was also a weak effect of illumination level on acuity and contrast sensitivity, both worsening with decreasing illumination. Recognition performance was best predicted by contrast sensitivity, whereas confidence was best predicted by visual acuity. CONCLUSIONS: Illumination variation over a typical photopic range in an indoor space had minimal effect on the objective visibility of steps and ramps for people with low vision. However, illumination level affected subjects' confidence in hazard recognition. Design decisions on parameters such as illumination should consider the consequences on both the objective and the subjective accessibility of a space.

Customizing spatial remapping of letters to aid reading in the presence of a simulated central field loss.

Reading is a primary concern of patients with central field loss (CFL) because it is typically performed with foveal vision. Spatial remapping offers one potential avenue to aid in reading; it entails shifting occluded letters to retinal areas where vision is functional. Here, we introduce a method of creating and testing different remapping strategies-ways to remap text-customized for CFL of different shapes. By simulating CFL in typically-sighted individuals, we tested the customization hypothesis-that the benefits of different remapping strategies will depend on the properties of the CFL. That is, remapping strategies will aid reading differentially in the presence of differently shaped CFL. In Experiment 1, letter recognition in the presence of differently shaped CFL was assessed in and around central vision. Using these letter recognition "maps" different spatial remappings were created and tested in Experiment 2 using a word recognition task. Results showed that the horizontal gap remapping, which did not remap any letters vertically, resulted in the best word recognition. Results were also consistent with the customization hypothesis; the benefits of different remappings on word recognition depended on the different CFL shapes. Although the horizontal gap remapping resulted in very good word recognition, tailoring remapping strategies to the shape of patients' CFL may aid reading with the wide range of sizes and shapes encountered by patients with CFL.

Developing pre-licensure interprofessional and stroke care competencies through skills-based simulations.

Interprofessional collaboration (IPC) in stroke care is accepted as best practice and necessary given the multi-system challenges and array of professionals involved. Our two-part stroke team simulations offer an intentional interprofessional educational experience (IPE) embedded in pre-licensure occupational therapy, physical therapy, pharmacy, medicine, nursing and speech-language pathology curricula. This six-year mixed method program evaluation aimed to determine if simulation delivery differences necessitated by COVID-19 impacted students' IPC perception, ratings, and reported learning. Following both simulations, the Interprofessional Collaborative Competency Assessment Scale (ICCAS) and free-text self-reported learning was voluntarily and anonymously collected. A factorial ANOVA using the ICCAS interprofessional competency factors compared scores across delivery methods. Content and category analysis was done for free-text responses. Overall, delivery formats did not affect positive changes in pre-post ICCAS scores. However, pre and post ICCAS scores were significantly different for interprofessional competencies of roles/responsibilities and collaborative patient/family centered approach. Analysis of over 10,000 written response to four open-ended questions revealed the simulation designs evoked better understanding of others' and own scope of practice, how roles and shared leadership change based on context and client need, and the value of each team member's expertise. Virtual-experience-only students noted preference for an in-person stroke clinic simulation opportunity.

Change in prevalence of preterm birth in Israel following publication of national guidelines recommending routine sonographic cervical-length measurement at 19-25 weeks' gestation.

OBJECTIVE: To compare the prevalence of preterm birth (PTB) (delivery before 37 weeks) in Israel before and after publication of national guidelines recommending second-trimester sonographic cervical-length (CL) measurement. METHODS: The Israeli Society of Obstetrics and Gynecology (ISOG) guidelines, issued on 1 January 2012, specified that CL should be measured transabdominally or, if this is not possible, transvaginally, at the 19-25-week ultrasound anomaly scan and that CL < 25 mm should indicate further work-up and treatment, although the type of treatment was unspecified. In 2000, the Israel Ministry of Health issued a legal requirement for the submission of delivery records to a national registry. These data were used to compare PTB prevalence in the period before (2000-2011) and that after (2012-2020) publication of the guidelines, as well as trends within each time period. Information was available on singleton and multiple pregnancy and maternal age and parity, as well as low birth weight (< 2500 g). RESULTS: During the period 2000-2020, there were 3 403 976 infants liveborn in Israel: 1 797 657 before and 1 606 319 after publication of the ISOG guidelines. There were 247 187 PTBs overall, with a prevalence of 7.64% (95% CI, 7.52-7.77%) before publication of the guidelines and 6.84% (95% CI, 6.43-7.24%) afterwards (P < 0.0002, two-tailed). The annual PTB prevalence was static in the first time period but declined by 0.18% per annum during the second period, after publication of the guidelines. The proportionate reduction in PTB prevalence after compared with before publication of the guidelines was 10% overall, 9% for PTB at 33-36 weeks, 18% for PTB at 28-32 weeks and 24% for PTB at < 28 weeks. After publication of the guidelines, reduced prevalence of PTB was observed among singletons (5.49% before vs 4.83% after, P < 0.0001), but not among infants in twin or higher-order multiple pregnancy. There was a statistically significant reduction in the rate of PTB following publication of the guidelines in both nulliparous and parous women and in the 19-39-year-old maternal-age group. Although reductions in PTB prevalence were also noted in high-risk age groups (maternal age < 19 years and ≥ 40 years), these did not reach statistical significance. Following publication of the guidelines, there was a statistically significant reduction in the prevalence of birth weight under 2500 g, of a magnitude similar to that for PTB prevalence. CONCLUSIONS: The publication of national guidelines recommending routine CL measurement at the time of the second-trimester anomaly scan was associated with a fall in PTB prevalence in singleton pregnancies. Whilst direct evidence linking screening with this fall in prevalence is lacking, it is likely that implementation of routine CL screening played an important role in the reduction of PTB rate. Our experience indicates that screening can be incorporated into the second-trimester anomaly scan. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Concept for gradient-free MRI on twin natural slices.

OBJECTIVE: The design of an MRI for use in space requires that the hardware be kept to an absolute minimum in terms of mass, complexity, and power. In addition, NASA requirements are that the external stray field needs to be less than 3.2 Gauss, 7 cm from the MRI enclosure. THEORY: RF encoding designs with Halbach magnets offer the best chance of meeting those requirements. Spatially non-uniform magnetic fields with foliations of isomagnetic surfaces, or natural slices, may be used to provide slice selection, and to reduce further the hardware complexity, for TRansmit Array Spatial Encoding (TRASE) Magnetic Resonance Imaging (MRI) or potentially for other radio frequency (RF) encoding methods. The design of such non-uniform magnetic fields in a Halbach configuration with built-in axial gradients leads to pairs of isomagnetic surfaces centered on either side of a central maximum field strength slice. If TRASE images from slices other than the central isomagnetic surface are desired, then the Nuclear Magnetic Resonance (NMR) signals originating from the twin natural slices must be separated during image reconstruction. Here, a design for simultaneously imaging on twin slices in such an inhomogeneous magnetic field using multiple receiver coils with spatially varying RF profiles is described mathematically and numerical simulation examples are given. DESIGN APPROACH: To achieve RF encoding on the natural slices, at least three TRASE transmit coils are required. Here a solution with twisted solenoid coils is given. To achieve the twin slice separation at least two receive coils are required. Here a solution with two solenoids is given. DISCUSSION: The MRI design presented here uses a combination of RF encoding (TRASE), a spatial encoding magnetic field (SEM, pairs of natural slices) and receive coil spatial profiles to encode enough information into the NMR signal for image slice reconstruction. The design presented here enables using Halbach magnets with a built-in axial gradient to be used for MRI. CONCLUSION: The result is a new gradient-free TRASE MRI design capable of imaging pairs of electronically selectable axial slices.

Delayed intubation associated with in-hospital mortality in patients with COVID-19 respiratory failure who fail heated and humified high flow nasal canula.

BACKGROUND: Advanced respiratory support modalities such as non-invasive positive pressure ventilation (NiPPV) and heated and humidified high flow nasal canula (HFNC) served as useful alternatives to invasive mechanical ventilatory support for acute respiratory failure (ARF) during the peak of the SARS-CoV-2/COVID-19 pandemic. Unlike NiPPV, HFNC is a newer modality and its role in the treatment of patients with severe ARF is not yet clearly defined. Furthermore, the characteristics of responders versus non-responders to HFNC have not been determined. Although recent evidence indicates that many patients with ARF treated with HFNC survive without needing intubation, those who fail and are subsequently intubated have worse outcomes. Given that prolonged use of HFNC in patients with ARF might exacerbate patient self-inflicted lung injury, we hypothesized that among those patients with ARF due to COVID-19 pneumonia, prolonged HFNC beyond 24 h before intubation would be associated with increased in-hospital mortality. METHODS: This was a retrospective, multicenter, observational cohort study of 2720 patients treated for ARF secondary to SARS-CoV-2/COVID-19 pneumonia and initially managed with HFNC within the Banner Health system during the period from March 1st, 2020, to July 31st, 2021. In the subgroup of patients for went from HFNC to IMV, we assessed the effect of the duration of HFNC prior to intubation on mortality. RESULTS: 1392 (51%) were successfully treated with HFNC alone and 1328 (49%) failed HFNC and were intubated (HFNC to IMV). When adjusted for the covariates, HFNC duration less than 24 h prior to intubation was significantly associated with reduced mortality. CONCLUSIONS: Among patients with ARF due to COVID-19 pneumonia who fail HFNC, delay of intubation beyond 24 h is associated with increased mortality.

Reconciling print-size and display-size constraints on reading.

Two fundamental constraints limit the number of characters in text that can be displayed at one time-print size and display size. These dual constraints conflict in two important situations-when people with normal vision read text on small digital displays, and when people with low vision read magnified text. Here, we describe a unified framework for evaluating the joint impact of these constraints on reading performance. We measured reading speed as a function of print size for three digital formats (laptop, tablet, and cellphone) for 30 normally sighted and 10 low-vision participants. Our results showed that a minimum number of characters per line is required to achieve a criterion of 80% of maximum reading speed: 13 characters for normally sighted and eight characters for low-vision readers. This critical number of characters is nearly constant across font and display format. Possible reasons for this required number of characters are discussed. Combining these character count constraints with the requirements for adequate print size reveals that an individual's use of a small digital display or the need for magnified print can shrink or entirely eliminate the range of print size necessary for achieving maximum reading speed.

Effect of expansive optic flow and lateral motion parallax on depth estimation with normal and artificially reduced acuity.

When an observer moves in space, the retinal projection of a stationary object either expands if the motion is toward the object or shifts horizontally if the motion contains a lateral component. This study examined the impact of expansive optic flow and lateral motion parallax on the accuracy of depth perception for observers with normal or artificially reduced acuity and asked whether any benefit is due to the continuous motion or to the discrete object image displacement. Stationary participants viewed a virtual room on a computer screen. They used an on-screen slider to estimate the depth of a target object relative to a reference object after seeing 2-second videos simulating five conditions: static viewing, expansive optic flow, and lateral motion parallax in either continuous motion or image displacement. Ten participants viewed the stimuli with normal acuity in Experiment 1 and 11 with three levels of artificially reduced acuity in Experiment 2. Linear regression models represented the relationship between the depth estimates of participants and the ground truth. Lateral motion parallax produced more accurate depth estimates than expansive optic flow and static viewing. Depth perception with continuous motion was more accurate than that with displacement under mild and moderate, but not severe, acuity reduction. For observers with both normal and artificially reduced acuity, lateral motion parallax was more helpful for object depth estimation than expansive optic flow, and continuous motion parallax was more helpful than object image displacement.

Digital Reading with Low Vision: Principles for Selecting Display Size.

SIGNIFICANCE: Digital reading devices have become increasingly popular among people with low vision. Because displays come in many sizes ranging from smart watches to large desktop computer displays, it is important to have principles to guide people with low vision in selecting suitable displays for reading. PURPOSE: The selection of effective digital displays for reading by people with low vision focuses attention on the interacting effects of print size, display size, font, visual acuity, and reading distance. This technical report aims to provide principles for identifying the minimum size of digital displays required for fluent reading by people with low vision. METHODS: We emphasize two critical factors in selecting an appropriate reading display: angular print size, which should exceed the individual's critical print size, and display size, which should allow at least 13 characters to be presented on each line. Our approach considers a low-vision individual's acuity and preferences for viewing distance and fonts. RESULTS: Through an illustrative example, we demonstrate how our approach can be used to determine display size for a low-vision individual with 20/200 acuity and central field loss who wants to read at 30-cm viewing distance with the Times Roman font. We have developed a web application based on our recommended approach to provide easy access to our algorithm. CONCLUSIONS: We provide a procedure to guide the selection of appropriate displays for a wide range of acuities. Our approach can help clinicians in making recommendations for their patients, digital product designers in developing more accessible devices, and low-vision individuals in selecting digital displays for reading.

How frail is frail? A systematic scoping review and synthesis of high impact studies.

AIMS: While the frailty index (FI) is a continuous variable, an FI score of 0.25 has construct and predictive validity to categorise community-dwelling older adults as frail or non-frail. Our study aimed to explore which FI categories (FI scores and labels) were being used in high impact studies of adults across different care settings and why these categories were being chosen by study authors. METHODS: For this systematic scoping review, Medline, Cochrane and EMBASE databases were searched for studies that measured and categorised an FI. Of 1314 articles screened, 303 met the eligibility criteria (community: N = 205; residential aged care: N = 24; acute care: N = 74). For each setting, the 10 studies with the highest field-weighted citation impact (FWCI) were identified and data, including FI scores and labels and justification provided, were extracted and analysed. RESULTS: FI scores used to distinguish frail and non-frail participants varied from 0.12 to 0.45 with 0.21 and 0.25 used most frequently. Additional categories such as mildly, moderately and severely frail were defined inconsistently. The rationale for selecting particular FI scores and labels were reported in most studies, but were not always relevant. CONCLUSIONS: High impact studies vary in the way they categorise the FI and while there is some evidence in the community-dweller literature, FI categories have not been well validated in acute and residential aged care. For the time being, in those settings, the FI should be reported as a continuous variable wherever possible. It is important to continue working towards defining frailty categories as variability in FI categorisation impacts the ability to synthesise results and to translate findings into clinical practice.

Chemical Speciation and Stability of Uranium in Unconventional Shales: Impact of Hydraulic Fracture Fluid.

Uranium and other radionuclides are prominent in many unconventional oil/gas shales and is a potential contaminant in flowback/produced waters due to the large volumes/types of chemicals injected into the subsurface during stimulation. To understand the stability of U before and after stimulation, a geochemical study of U speciation was carried out on three shales (Marcellus, Green River, and Barnett). Two types of samples for each shale were subjected to sequential chemical extractions: unreacted and shale-reacted with a synthetic hydraulic fracture fluid. A significant proportion of the total U (20-57%) was released from these three shales after reaction with fracture fluid, indicating that U is readily leachable. The total U released exceeds labile water-soluble and exchangeable fractions in unreacted samples, indicating that fluids leach more recalcitrant phases in the shale. Radiographic analysis of unreacted Marcellus shale thin sections shows U associated with detrital quartz and the clay matrix in the shale. Detrital zircon and TiO2 identified by an electron microprobe could account for the hot spots. This study shows that significant proportions of U in three shales are mobile upon stimulation. In addition, the extent of mobilization of U depends on the U species in these rocks.

Redox Heterogeneities Promote Thioarsenate Formation and Release into Groundwater from Low Arsenic Sediments.

Groundwater contamination by As from natural and anthropogenic sources is a worldwide concern. Redox heterogeneities over space and time are common and can influence the molecular-level speciation of As, and thus, As release/retention but are largely unexplored. Here, we present results from a dual-domain column experiment, with natural organic-rich, fine-grained, and sulfidic sediments embedded as lenses (referred to as "reducing lenses") within natural aquifer sand. We show that redox interfaces in sulfur-rich, alkaline aquifers may release concerning levels of As, even when sediment As concentration is low (<2 mg/kg), due to the formation of mobile thioarsenates at aqueous sulfide/Fe molar ratios <1. In our experiments, this behavior occurred in the aquifer sand between reducing lenses and was attributed to the spreading of sulfidic conditions and subsequent Fe reductive dissolution. In contrast, inside reducing lenses (and some locations in the aquifer) the aqueous sulfide/Fe molar ratios exceeded 1 and aqueous sulfide/As molar ratios exceeded 100, which partitioned As(III)-S to the solid phase (associated with organics or as realgar (As4S4)). These results highlight the importance of thioarsenates in natural sediments and indicate that redox interfaces and sediment heterogeneities could locally degrade groundwater quality, even in aquifers with unconcerning solid-phase As concentrations.

Online Survey of Digital Reading by Adults with Low Vision.

SIGNIFICANCE: Access to digital text is increasingly widespread, but its impact on low-vision reading is not well understood. PURPOSE: We conducted an online survey of people with low vision to determine what assistive technologies they use for visual reading, their preferred text characteristics, and the time they devote to reading digital and hard-copy text. METHODS: One hundred thirty-three low-vision participants completed an online survey. Participants reported the nature and history of their low vision, their usage of different assistive technologies, and time devoted to five visual reading activities. RESULTS: The three largest diagnostic categories were albinism (n = 36), retinitis pigmentosa (n = 20), and glaucoma (n = 15). Mean self-reported acuity was 0.93 logMAR (range, 0.1 to 1.6 logMAR). Mean age was 46 years (range, 18 to 98 years). Participants reported on percentage time spent reading using vision, audio, or touch (braille). Seventy-five percent of our participants did more than 50% of their reading visually. Across five categories of reading activities-work or education, news, pleasure, spot reading, and social networking-participants reported more time spent on digital reading than hard-copy reading. Eighty-nine percent of our participants used at least one technology from each of our two major categories of assistive technologies (digital content magnifiers and hard-copy content magnifiers) for visual reading. CONCLUSIONS: Despite the growing availability of digital text in audio or braille formats, our findings from an online sample of people with low vision indicate the continuing importance of visual reading. Our participants continue to use technology to access both hard-copy and digital text, but more time is devoted to digital reading. Our findings highlight the need for continued research and development of technology to enhance visual reading accessibility.

Supplementary prenatal copper increases plasma triiodothyronine and brown adipose tissue uncoupling protein-1 gene expression but depresses thermogenesis in newborn lambs.

OBJECTIVE: We tested the hypothesis that increasing dietary copper (Cu) to gravid ewes would enhance brown adipose tissue (BAT) thermogenesis in their offspring. METHODS: Twin-bearing ewes were assigned on d 70 of gestation to diets containing 3, 10, or 20 ppm dietary Cu (n = 8 per group). Twin lambs were assigned at birth to a cold (6°C) or warm (28°C) environmental chamber for 48 h. Blood was collected from ewes and from lambs and perirenal BAT was collected after 48 h in the environmental chambers. RESULTS: Prenatal Cu exposure increased ewe plasma triiodothyronine (T3) and thyroxine concentration (T4) (p &lt; 0.01) but prenatal Cu exposure had no effect on lamb plasma concentrations of T3, T4, glucose, or nonesterified fatty acid concentration (p ≥ 0.08). The high level of prenatal Cu exposure depressed 48-h rectal temperature (p = 0.03). Cold exposure decreased BAT norepinephrine (NE) and increased BAT dopamine (p ≤ 0.01), but prenatal Cu exposure had no effect on BAT cytochrome C oxidase activity or BAT NE or dopamine (p ≥ 0.07). However, BAT of lambs from high-Cu ewes maintained higher uncoupling protein-1 (UCP1) gene expression than BAT of lambs from low- and medium-Cu ewes following warm or cold exposure in environmental chambers (p = 0.02). Cold exposure caused near depletion of BAT lipid by 48 h (p &lt; 0.001), increased BAT cytochrome c oxidase activity (p &lt; 0.01), and depressed plasma fatty acid concentrations (p &lt; 0.001). CONCLUSION: Although prenatal Cu exposure increased BAT UCP1 expression during warm and cold exposure, prenatal cold Cu exposure depressed 48-h rectal temperature. Cold exposure decreased BAT lipid content by over 80% and decreased lamb plasma fatty acid concentration by over 40%, indicating that fuel reserves for thermogenesis were nearly depleted by 48 h of cold exposure.

Kaposi Sarcoma Herpesvirus Inflammatory Cytokine Syndrome-like Clinical Presentation in Human Immunodeficiency Virus-infected Children in Malawi.

We describe 7 human immunodeficiency virus-infected Malawian children with Kaposi sarcoma who met criteria for Kaposi sarcoma herpesvirus (KSHV) inflammatory cytokine syndrome. Each presented with persistent fevers, bulky lymphadenopathy, massive hepatosplenomegaly, and severe cytopenias. Plasma analyses were performed in 2 patients, both demonstrating extreme elevations of KSHV viral load and interleukin 6.

KSHV viral load and Interleukin-6 in HIV-associated pediatric Kaposi sarcoma-Exploring the role of lytic activation in driving the unique clinical features seen in endemic regions.

Kaposi sarcoma (KS) is among the most common childhood malignancies in central, eastern, and southern Africa. Although its unique clinical features have been established, biological mechanisms related to the causative agent, KS-associated herpes-virus (KSHV), have yet to be explored in children. We performed a prospective observational pilot study to explore associations between KSHV viral load (VL), human interleukin-6 (IL-6) and IL-10 levels, and clinical characteristics of 25 children with KS in Lilongwe, Malawi from June 2013-August 2015. The median age was 6.4 years. Lymphadenopathy was the most common site of KS involvement (64%), followed by skin and oral mucosa (44% each), woody edema (12%), and pulmonary (8%). Baseline samples for plasma KSHV VL, IL-6 and IL-10 analyses were available for 18/25 patients (72%) at time of KS diagnosis. KSHV VL was detectable at baseline in 12/18 (67%) patients, the median baseline IL-6 level was 8.53 pg/mL (range 4.31-28.33), and the median baseline IL-10 level was 19.53 pg/mL (range 6.91-419.69). Seven (39%) patients presented with an IL-6 level > 10 pg/mL (exceeding twice the upper limit of normal). Detectable KSHV VL was significantly associated with lymphadenopathic KS (p = 0.004), while having undetectable KSHV VL was associated with a higher likelihood of presenting with hyperpigmented skin lesions (p = 0.01). Detectable KSHV VL and elevated IL-6 levels are present in a subset of children with KS. Lytic activation of KSHV and associated elevation in KSHV VL may contribute to the unique clinical manifestations of pediatric KS in KSHV-endemic regions of Africa.

Gaze behavior during navigation with reduced acuity.

Navigating unfamiliar indoor spaces while visually searching for objects of interest is a challenge faced by people with visual impairment. We asked how restricting visual acuity of normally sighted subjects would affect visual search and navigation in a real world environment, and how their performance would compare to subjects with naturally occurring low vision. Two experiments were conducted. In the first, 8 normally sighted subjects walked along an indoor path, looking for objects placed at unpredictable intervals to the left and right of the path, and identified single letters posted on the objects. A head-mounted eye tracker was used to assess their gaze direction in the environment. For half the trials, blur foils were used to restrict visual acuity to approximately logMAR 1.65. Gaze behavior, travel time, and letter recognition accuracy were compared between blurred and unrestricted conditions. In the second experiment, the same procedure was conducted, but performance was compared between acuity-restricted normally-sighted subjects and subjects with naturally occurring low vision (mean acuity 1.09 logMAR, range 0.48-1.85 logMAR). In Experiment 1, neither Blur nor the Letter Recognition Task individually had a statistically significant effect on travel time. However, when combined, there was an interaction between the two that increased travel time by approximately 63%, relative to baseline trials. Blur modified gaze behavior such that subjects spent more time looking down toward the floor while walking, at the expense of time spent looking in other directions. During Letter Recognition Task trials with Blur, subjects spent extra time examining objects, though more objects were missed altogether. In Experiment 2, low-vision subjects spent more time looking toward the boundary between the floor and the wall, but gaze patterns were otherwise similar to acuity-restricted subjects with normal vision. Low-vision subjects were also more likely to miss objects compared to acuity-restricted subjects. We conclude that under conditions of artificially restricted acuity, normally sighted subjects look downward toward the floor more frequently while navigating and take extra time to examine objects of interest, but are less likely to detect them. Low-vision subjects tend to direct their gaze toward the boundary between the wall and the floor, which may serve as a high contrast cue for navigation.