Quantifying functional group compositions of household fuel-burning emissions.

Globally, billions of people burn fuels indoors for cooking and heating, which contributes to millions of chronic illnesses and premature deaths annually. Additionally, residential burning contributes significantly to black carbon emissions, which have the highest global warming impacts after carbon dioxide and methane. In this study, we use Fourier transform infrared spectroscopy (FTIR) to analyze fine-particulate emissions collected on Teflon membrane filters from 15 cookstove types and 5 fuel types. Emissions from three fuel types (charcoal, kerosene, and red oak wood) were found to have enough FTIR spectral response for functional group (FG) analysis. We present distinct spectral profiles for particulate emissions of these three fuel types. We highlight the influential FGs constituting organic carbon (OC) using a multivariate statistical method and show that OC estimates by collocated FTIR and thermal-optical transmittance (TOT) are highly correlated, with a coefficient determination of 82.5 %. As FTIR analysis is fast and non-destructive and provides complementary FG information, the analysis method demonstrated herein can substantially reduce the need for thermal-optical measurements for source emissions.

Metastatic Renal Cell Carcinoma in a Patient With Autosomal Dominant Polycystic Kidney Disease.

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) manifests as multiple cysts in the kidneys and liver but can also present with musculoskeletal and cardiovascular abnormalities. ADPKD patients are at increased risk for renal cell carcinoma development. We show the FDG PET/CT findings in a patient with renal cell carcinoma secondary to ADPKD and complicated by worsening pulmonary metastasis. The primary renal tumor shows intense FDG uptake despite no suspicious features with contrast CT.

The Effects of Residual Femoral Deformity on Computed Contact Mechanics in Patients Treated With In Situ Fixation for Slipped Capital Femoral Epiphysis.

OBJECTIVE: In situ fixation for treatment of slipped capital femoral epiphysis (SCFE) can stabilize the epiphysis and prevent further joint deformation but often leaves residual deformity that may adversely affect intra-articular contact mechanics. The purpose of this study was to investigate the relationship between residual deformity and contact mechanics in the post-SCFE hip. METHODS: Patient-specific hip models were created for 19 patients with SCFE treated with in situ fixation. For each model, discrete element analysis was used to compute cumulative acetabular and femoral contact stress exposure during a walking gait cycle. Slip severity was evaluated for each patient using the two-dimensional Southwick angle and a novel three-dimensional (3D) assessment of multiplanar femoral deformity (3D slip angle). RESULTS: Of the SCFE cases, 2/7 mild (Southwick angle ≤30 degrees) had peak cumulative femoral exposures equivalent to that of severe (Southwick angle ≥60 degrees) cases. Severe SCFE cases had higher peak ( P = 0.015) and mean ( P = 0.028) femoral contact stress exposure and lower cumulative femoral contact area ( P = 0.003) than mild (Southwick angle ≤30 degrees) SCFE cases. Mean femoral contact stress exposure was also higher in severe SCFE cases than in moderate SCFE cases ( P = 0.027). Acetabular and femoral contact mechanics metrics typically demonstrated stronger correlations with 3D slip angle than two-dimensional Southwick angle. CONCLUSIONS: Increased slip severity adversely impacts intra-articular femoral contact mechanics. Contact mechanics metrics demonstrate higher correlations with 3D slip angle, indicating that this novel measurement may better describe global deformity and its relationship to intra-articular mechanics; however, the modest strength of these correlations may also imply that global impingement-generating deformity is not the primary factor driving contact mechanics in the post-SCFE hip. CLINICAL RELEVANCE: Greater slip severity adversely impacts contact mechanics in the post-SCFE hip. However, focal regions of high contact stress were seen even in mild SCFE deformities, suggesting some type of deformity correction should be considered even for mild slips to alleviate secondary impingement, address focal incongruities, and reduce osteoarthritis development/progression.

Magmatic immiscibility and the origin of magnetite-(apatite) iron deposits.

The origin of magnetite-(apatite) iron deposits (MtAp) is one of the most contentious issues in ore geology with competing models that range from hydrothermal to magmatic processes. Here we report melt inclusions trapped in plagioclase phenocrysts in andesite hosting the MtAp mineralization at El Laco, Chile. The results of our study reveal that individual melt inclusions preserve evidence of complex processes involved in melt immiscibility, including separation of Si- and Fe-rich melts, the latter hosting Cu sulfide-rich, phosphate-rich, and residual C-O-HFSE-rich melts, with their melting temperature at 1145 °C. This association is consistent with the assemblages observed in the ore, and provides a link between silicate and Fe-P-rich melts that subsequently produced the magnetite-rich magmas that extruded on the flanks of the volcano. These results strongly suggest that the El Laco mineralization was derived from crystallization of Fe-P-rich melts, thus providing insight into the formation of similar deposits elsewhere.

Reductions in Children's Blood Lead Levels from a Drinking-Water Intervention in Madagascar, Sub-Saharan Africa.

One in three children globally is estimated to have blood lead levels (BLL) at or above the BLL reference value of 5 µg/dL with increased burden falling on low- and middle-income countries (LMIC). Within developed countries, aqueous lead is the predominant exposure route. However, aqueous lead exposure is rarely examined in the LMIC, leaving a gap in the literature that ignores a potentially significant route of exposure. Furthermore, limited lead-based remediation efforts around consumer products have been examined. This study investigates the importance of lead exposure from the water supply through a case study in Toamasina, Madagascar. The project measured aqueous lead and BLL of children pre- and postremediation efforts (i.e., removal of leaded pump components in hand pumps) to verify the impact of aqueous lead exposure within this community. Removal of the leaded pump components (i.e., piston and foot valves) and replacement with nonleaded components decreased aqueous lead levels below the World Health Organization provisional guideline of 10 µg/L in all but 4% of pumps tested. Measured BLL concentrations indicated a statistically significant decrease in BLL from pre- to postremediation. Furthermore, the remediation resulted in a decrease in BLL for 87% of children with the greatest changes in BLL observed for children with the highest preremediation concentrations. These findings point to a need for greater consideration of lead in drinking and cooking waters as an important exposure route in LMIC.

The Combined Utilization of Epithelial Thickness Mapping and Tomography in Keratorefractive Surgery Screening: One Imaging Modality is Not Sufficient.

Increasing popularity and utility of epithelial thickness mapping (ETM) in keratorefractive surgery screening may begin to inappropriately devalue the use of tomography. An increasing body of research suggests that the interpretation of ETM based solely on the corneal resurfacing function may be insufficient to screen and select patients for refractive surgery. ETM and tomography are complementary and, when used together, may provide the safest and most optimal tools for keratorefractive surgery screening.

A flexible proton beam imaging energy spectrometer (PROBIES) for high repetition rate or single-shot high energy density (HED) experiments (invited).

The PROBIES diagnostic is a new, highly flexible, imaging and energy spectrometer designed for laser-accelerated protons. The diagnostic can detect low-mode spatial variations in the proton beam profile while resolving multiple energies on a single detector or more. When a radiochromic film stack is employed for "single-shot mode," the energy resolution of the stack can be greatly increased while reducing the need for large numbers of films; for example, a recently deployed version allowed for 180 unique energy measurements spanning ∼3 to 75 MeV with <0.4 MeV resolution using just 20 films vs 180 for a comparable traditional film and filter stack. When utilized with a scintillator, the diagnostic can be run in high-rep-rate (>Hz rate) mode to recover nine proton energy bins. We also demonstrate a deep learning-based method to analyze data from synthetic PROBIES images with greater than 95% accuracy on sub-millisecond timescales and retrained with experimental data to analyze real-world images on sub-millisecond time-scales with comparable accuracy.

Comparative Visual Outcome Analysis of a Diffractive Multifocal Intraocular Lens and a New Diffractive Multifocal Lens with Extended Depth of Focus.

This study compares the visual and refractive performance of the TECNIS Synergy (DFR00V-DFW150-225-300-375) multifocal intraocular lens (IOL) and the AcrySof IQ PanOptix (TFAT00-30-40-50-60) multifocal IOL. Patients who underwent phacoemulsification and cataract extraction and received either a multifocal Synergy or PanOptix IOL were included. Monocular uncorrected distance (UDVA), intermediate (UIVA), near (UNVA), and corrected distance (CDVA) visual acuities were assessed at three and six months postoperatively. Secondary outcome measures of photic phenomena were also assessed. A total of 140 patients (224 eyes) were included in this study, with 69 patients (105 eyes) in the Synergy group and 71 patients (119 eyes) in the PanOptix group. There were no statistically significant differences in UIVA or CDVA measurements across all time points. When assessing UDVA, at three months postoperatively, there were more eyes in the PanOptix group with vision better than 20/40 (p = 0.04). At three and six months postoperatively, the average UNVA was superior in the Synergy group (p = 0.01, 0.002). While the Synergy group reported more night vision disturbances at one and three months (p = 0.01, 0.03), the PanOptix group had more night vision disturbances at six months (p = 0.02). Although not statistically significant, the AcrySof IQ PanOptix multifocal IOL demonstrated better UDVA and UIVA sooner postoperatively than the TECNIS Synergy multifocal IOL. The Synergy IOL provided statistically better UNVA compared to the PanOptix IOL at three and six months postoperatively. Synergy patients reported more early photic phenomena than PanOptix patients, which later diminished.

Corneal Refractive Surgery Considerations in Patients with Cystic Fibrosis and Cystic Fibrosis Transmembrane Conductance Regulator-Related Disorders.

This article discusses common ocular manifestations of cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator-related disorders (CFTR-RD). A structured approach for assessing and treating patients with CF/CFTR-RD seeking corneal refractive surgery is proposed, as well as a novel surgical risk scoring system. We also report two patients with various manifestations of CFTR dysfunction who presented for refractive surgery and the outcomes of the procedures. Surgeons seeking to perform refractive surgery on patients with CF/CFTR-RD should be aware of mild to severe clinical manifestations of CFTR dysfunction. Specific systemic and ocular manifestations of CF include chronic obstructive pulmonary disease (COPD), bronchiectasis, recurrent pulmonary infections, CF-related diabetes and liver disease, pancreatic insufficiency, conjunctival xerosis, night blindness, meibomian gland dysfunction (MGD), and blepharitis. Corneal manifestations include dry eye disease (DED), punctate keratitis (PK), filamentary keratitis (FK), xerophthalmia, and decreased endothelial cell density and central corneal thickness. Utilization of the appropriate review of systems (ROS) and screening tests will assist in determining if the patient is a suitable candidate for refractive surgery, as CF/CFTR-RD can impact the health of the cornea. Collaboration with other medical professionals who care for these patients is encouraged to ensure that their CF/CFTR-RD symptoms are best controlled via systemic and other treatment options. This will assist in reducing the severity of their ocular manifestations before and after surgery.

Depletion of COPI in cancer cells: the role of reactive oxygen species in the induction of lipid accumulation, noncanonical lipophagy and apoptosis.

The coatomer protein complex 1 (COPI) is a multisubunit complex that coats intracellular vesicles and is involved in intracellular protein trafficking. Recently we and others found that depletion of COPI complex subunits zeta (COPZ1) and delta (ARCN1) preferentially kills tumor cells relative to normal cells. Here we delineate the specific cellular effects and sequence of events of COPI complex depletion in tumor cells. We find that this depletion leads to the inhibition of mitochondrial oxidative phosphorylation and the elevation of reactive oxygen species (ROS) production, followed by accumulation of lipid droplets (LDs) and autophagy-associated proteins LC3-II and SQSTM1/p62 and, finally, apoptosis of the tumor cells. Inactivation of ROS in COPI-depleted cells with the mitochondrial-specific quencher, mitoquinone mesylate, attenuated apoptosis and markedly decreased both the size and the number of LDs. COPI depletion caused ROS-dependent accumulation of LC3-II and SQSTM1 which colocalizes with LDs. Lack of double-membrane autophagosomes and insensitivity to Atg5 deletion suggested an accumulation of a microlipophagy complex on the surface of LDs induced by depletion of the COPI complex. Our findings suggest a sequence of cellular events triggered by COPI depletion, starting with inhibition of oxidative phosphorylation, followed by ROS activation and accumulation of LDs and apoptosis.

Development and Testing of a Communication Intervention to Improve Chronic Pain Management in Primary Care: A Pilot Randomized Clinical Trial.

OBJECTIVES: Effective communication skills are essential for optimally managing chronic pain and opioids. This exploratory, sequential mixed methods study tested the effect of a novel framework designed to improve pain-related communication and outcomes. METHODS: Study 1 developed a novel 5-step framework for helping primary care clinicians discuss chronic pain and opioids with patients. Study 2 pilot tested an intervention for teaching this framework using standardized patient instructors-actors trained to portray patients and provide immediate clinician feedback-deployed during regular clinic hours. Primary care physicians were randomized to receive either the intervention or pain management recommendations from the Centers for Disease Control and Prevention. Primary outcomes were pain-related interference at 2 months and clinician use of targeted communication skills (coded from transcripts of audio-recorded visits); secondary outcomes were pain intensity at 2 months, clinician self-efficacy for communicating about chronic pain, patient experience, and clinician-reported visit difficulty. RESULTS: We enrolled 47 primary care physicians from 2 academic teaching clinics and recorded visits with 48 patients taking opioids for chronic pain who had an appointment scheduled with an enrolled physician. The intervention was not associated with significant changes in primary or secondary outcomes other than clinician self-efficacy, which was significantly greater in the intervention group. DISCUSSION: This study developed a novel framework and intervention for teaching clinician pain-related communications skills. Although the intervention showed promise, more intensive or multicomponent interventions may be needed to have a significant impact on clinicians' pain-related communication and pain outcomes.

Automated Nuclear Segmentation in Head and Neck Squamous Cell Carcinoma Pathology Reveals Relationships between Cytometric Features and ESTIMATE Stromal and Immune Scores.

The tumor microenvironment (TME) plays an important role in the progression of head and neck squamous cell carcinoma (HNSCC). Currently, pathologic assessment of TME is nonstandardized and subject to observer bias. Genome-wide transcriptomic approaches to understanding the TME, while less subject to bias, are expensive and not currently a part of the standard of care for HNSCC. To identify pathology-based biomarkers that correlate with genomic and transcriptomic signatures of TME in HNSCC, cytometric feature maps were generated in a publicly available data set from a cohort of patients with HNSCC, including whole-slide tissue images and genomic and transcriptomic phenotyping (N = 49). Cytometric feature maps were generated based on whole-slide nuclear detection, using a deep-learning algorithm trained for StarDist nuclear segmentation. Cytometric features in each patient were compared to transcriptomic measurements, including Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) scores and stemness scores. With correction for multiple comparisons, one feature (nuclear circularity) demonstrated a significant linear correlation with ESTIMATE stromal score. Two features (nuclear maximum and minimum diameter) correlated significantly with ESTIMATE immune score. Three features (nuclear solidity, nuclear minimum diameter, and nuclear circularity) correlated significantly with transcriptomic stemness score. This study provides preliminary evidence that observer-independent, automated tissue-slide analysis can provide insights into the HNSCC TME which correlate with genomic and transcriptomic assessments.

Childhood blood lead levels and environmental risk factors in Madagascar.

One-third of children globally have blood lead levels (BLLs) exceeding the (former) US CDC reference value of 5 µg/dL; this value may be as high as one-half for children in low- and middle-income countries (LMICs). Lead exposure occurs through a variety of routes (e.g., water, dust, air), and in LMICs specifically, informal economies (e.g., battery recycling) can drive lead exposures due, in part, to absent regulation. Previous work by our team identified a ubiquitous source of lead (Pb), in the form of Pb-containing components used in manually operated pumps, in Toamasina, Madagascar. Characterization of BLLs of children exposed to this drinking water, and identification of additional exposure routes were needed. BLLs were measured for 362 children (aged 6 months to 6 years) in parallel with surveying to assess 14 risk factors related to demographics/socioeconomics, diet, use of pitcher pumps, and parental occupations. BLL data were also compared against a recent meta-review of BLLs for LMICs. Median childhood BLL (7.1 µg/dL) was consistent with those of other Sub-Saharan African LMICs (6.8 µg/dL) and generally higher than LMICs in other continents. Risk factors significantly associated (p < 0.05, univariate logistic regression) with elevated BLL (at ≥ 5 µg/dL) included male gender, living near a railway or major roadway (owing potentially to legacy lead pollution), having lower-cost flooring, daily consumption of foods (beans, vegetables, rice) commonly cooked in recycled aluminum pots (a previously identified lead source for this community), and a maternal occupation (laundry-person) associated with lower socioeconomic status (SES). Findings were similar at the ≥ 10 µg/dL BLL status. Our methods and findings may be appropriate in identifying and reducing lead exposures for children in other urbanizing cities, particularly in Sub-Saharan Africa, where lead exposure routes are complex and varied owing to informal economics and substantial legacy pollution.

Cookstove Emissions and Performance Evaluation Using a New ISO Protocol and Comparison of Results with Previous Test Protocols.

In 2018, the International Organization for Standardization (ISO) 19867-1 "Harmonized laboratory test protocols" were released for establishing improved quality and comparability for data on cookstove air pollutant emissions, efficiency, safety, and durability. This is the first study that compares emissions [carbon dioxide, carbon monoxide, total hydrocarbons, methane, nitrogen oxides, fine particulate matter (PM2.5), organic carbon, elemental carbon, and ultrafine particles] and efficiency data between the ISO protocol and the Water Boiling Test (WBT). The study examines six stove/fuel combinations [liquefied petroleum gas (LPG), pellet, wood fan, wood rocket, three stone fire, and charcoal] tested in the same US EPA laboratory. Evaluation of the ISO protocol shows improvements over previous test protocols and that results are relatively consistent with former WBT data in terms of tier ratings for emissions and efficiency, as defined by the ISO 19867-3 "Voluntary Performance Targets." Most stove types remain similarly ranked using ISO and WBT protocols, except charcoal and LPG are in higher PM2.5 tiers with the ISO protocol. Additionally, emissions data including polycyclic aromatic hydrocarbons are utilized to compare between the ISO and Firepower Sweep Test (FST) protocols. Compared to the FST, the ISO protocol results in generally higher PM2.5 tier ratings.

The effect of PEGylation on the efficacy and uptake of an immunostimulatory nanoparticle in the tumor immune microenvironment.

The efficacy of immunotherapies is often limited by the immunosuppressive tumor microenvironment, which is populated with dysfunctional innate immune cells. To reprogram the tumor-resident innate immune cells, we developed immunostimulatory silica mesoporous nanoparticles (immuno-MSN). The cargo of immuno-MSN is a Stimulator of Interferon Gene (STING) agonist, which activates innate immune cells leading to production of interferon (IFN) ß. By proficiently trafficking its cargo into immune cells, the immuno-MSN induced a 9-fold increase of IFN-ß secretion compared to free agonist. While an external PEG shield has historically been used to protect nanoparticles from immune recognition, a PEGylated immunostimulatory nanoparticle needs to strike a balance between immune evasion to avoid off-site accumulation and uptake by target immune cells in tumors. Using the 4T1 mouse model of metastatic breast cancer and flow cytometry, it was determined that the degree of PEGylation significantly influenced the uptake of 'empty' MSNs by tumor-resident innate immune cells. This was not the case for the agonist-loaded immuno-MSN variants. It should be noted the surface charge of the 'empty' MSNs was positive rather than neutral for the agonist-loaded immuno-MSNs. However, even though the cellular uptake was similar at 24 h after injection for the three immuno-MSN variants, we observed a significant beneficial effect on the activation and expansion of APCs especially in lung metastasis using the lightly PEGylated immuno-MSN variant.

Benchmarking total knee replacement constructs using noninferiority analysis: the New Zealand joint registry study.

BACKGROUND: The aim of this study was to compare the relative performance of total knee replacement constructs and discern if there is variability in performance in currently commonly used prostheses in the New Zealand Joint Registry (NZJR) using a noninferiority analysis. METHODS: All patients who underwent a primary total knee replacement (TKR) registered in the NZJR between 1st January 1999 to June 2020 were identified. Using a noninferiority analysis, the performance of total knee replacement prostheses were compared with the best performing contemporary construct. Construct all-cause revision rate was estimated using the 1-Kaplan Meier survival function method to estimate net failure. The difference in all-cause revision rates between the contemporary benchmark and all other constructs was tested. RESULTS: In total 110 183 TKR were recorded and 25 constructs (102 717 procedures) had > 500 procedures at risk at 3 years post-primary of which 5 were inferior by at least 20 % relative risk of which, one was inferior by at least 100 % relative risk. 14 constructs were identified with > 500 procedures at risk at 10 years with 5 inferior by at least 20 %, of which 2 were inferior by > 100 % relative risk. CONCLUSIONS: We discerned that there is great variability in construct performance and at all time points, greater than 25 % of constructs are inferior to the best performing construct by at least 20 %. These results can help inform patients, clinicians and health care funders when considering TKR surgery.

Immunostimulatory silica nanoparticle boosts innate immunity in brain tumors.

The high mortality associated with glioblastoma multiforme (GBM) is attributed to its invasive nature, hypoxic core, resistant cell subpopulations and a highly immunosuppressive tumor microenvironment (TME). To support adaptive immune function and establish a more robust antitumor immune response, we boosted the local innate immune compartment of GBM using an immunostimulatory mesoporous silica nanoparticle, termed immuno-MSN. The immuno-MSN was specifically designed for systemic and proficient delivery of a potent innate immune agonist to dysfunctional antigen-presenting cells (APCs) in the brain TME. The cargo of the immuno-MSN was cyclic diguanylate monophosphate (cdGMP), a Stimulator of Interferon Gene (STING) agonist. Studies showed the immuno-MSN promoted the uptake of STING agonist by APCs in vitro and the subsequent release of the pro-inflammatory cytokine interferon ß, 6-fold greater than free agonist. In an orthotopic GBM mouse model, systemically administered immuno-MSN particles were taken up by APCs in the near-perivascular regions of the brain tumor with striking efficiency. The immuno-MSNs facilitated the recruitment of dendritic cells and macrophages to the TME while sparing healthy brain tissue and peripheral organs, resulting in elevated circulating CD8+ T cell activity (2.5-fold) and delayed GBM tumor growth. We show that an engineered immunostimulatory nanoparticle can support pro-inflammatory innate immune function in GBM and subsequently augment current immunotherapeutic interventions and improve their therapeutic outcome.

Relative position of the supra-acetabular bone to the crestal plane: a radiological analysis.

INTRODUCTION: Displaced unstable pelvic injuries are life threatening and require rapid reduction and stabilisation, typically achieved with an external fixator. Recently, the benefits of supra-acetabular pins have been proven; however, these are usually inserted under fluoroscopic guidance. In austere environments and in extremis, this facility is limited and fixation using anatomical landmarks is required. Thus, the aim of this study is to determine the relative position of the supra-acetabular bone to the crestal plane and examine its consistency in military-aged European personnel. METHODS: A radiological review of 50 randomised pelvic CT scans in European patients aged 18-30 years from a Level 1 trauma centre was performed. The CT scans were analysed using 3D rendering software. The relative position of the supra-acetabular bone to the crestal plane was determined. RESULTS: The supra-acetabular bone relative to the crestal plane was approximately 28° caudal and 24° medial to the crestal plane. The mean minimum distance from the pin's entry point to the sciatic notch was approximately 73 mm. There were no differences noted between genders or hemipelvic side. CONCLUSIONS: The supra-acetabular bone maintains a consistent relative position to the crestal plane. Thus, with the surgeon's thumb on the anterior superior iliac spine (ASIS) and index finger on the iliac tubercle, defining the crestal plane, a supra-acetabular pin can be inserted into the anterior inferior iliac spine, which lies 3 cm inferior and 2 cm medial to the ASIS, and advanced along the supra-acetabular bone by angling the pin 30° caudal and 25° medial to the crestal plane.