University of California, Los Angeles

Building fair, equitable, and beneficial partnerships between institutions collaborating in research in low- and middle-income countries (LMIC) and high-income countries (HIC) has become an integral part of research capacity building in global health in recent years. In this paper, we offer an example of an academic collaboration between the University of California Los Angeles, Center for Health Policy and Research (UCLA CHPR) and the University of Philippines, Manila, College of Public Health (UPM CPH) that sought to build an equitable partnership between research institutions. The partnership was built on a project to build capacity for research and produce data for policy action for the prevention and care of non-communicable diseases (NCDs) through primary healthcare in the Philippines. The specific objectives of the project were to: (1) locally adapt the Primary Care Assessment Tool for the Philippines and use the adapted tool to measure facility-level primary care delivery, (2) conduct focus group discussions (FGDs) to gather qualitative observations regarding primary care readiness and capacity, and (3) conduct a comprehensive population-based health survey among adults on NCDs and prior healthcare experience. We describe here the progression of the partnership between these institutions to carry out the project and the elements that helped build a stronger connection between the institutions, such as mutual goal setting, cultural bridging, collaborative teams, and capacity building. This example, which can be used as a model depicting new directionality and opportunities for LMIC-HIC academic partnerships, was written based on the review of shared project documents, including study protocols, and written and oral communications with the project team members, including the primary investigators. The innovation of this partnership includes: LMIC-initiated project need identification, LMIC-based funding allocation, a capacity-building role of the HIC institution, and the expansion of scope through jointly offered courses on global health.

Offshore wind energy is an important agent to fight climate change. However, it is simultaneously very sensitive to climate change. This study analyzes the future changes in wind speed of 10 m above sea surface (V10) in the North Atlantic Ocean and how these variations may affect offshore wind energy resources for three potential subregions (the United States (US) East Coast, western Iberian Peninsula, and the Caribbean Sea). Dynamic downscaling of three different future scenarios of the CESM2 global climate model (CMIP6 project) was performed using the WRF-ARW atmospheric model. V10 is expected to decrease in the winter and spring seasons but increase in summer and autumn, mainly in tropical regions up to 30 °N. Annually, it shows the maximum increase in the tropical region. For the Iberian Peninsula subregion, significant increases in summer are expected for wind power density (WPD) along the 21st century, but there is uncertainty for the other seasons. A WPD decrease in winter and increases in summer and autumn are expected along the 21st century for the US subregion. No significant changes were observed at annual scale. Finally, for the Caribbean Sea, a decrease is projected in the Yucatan Basin and considerable increases are foreseen for the Colombia and Venezuela basins.

Industrial Internet of Things (IIoT) is experiencing rapid developments in the era of Industry 4.0. However, the ever-increasing applications put forwards higher requirements for authentication. Facing such a problem, researchers combine two cutting-edge techniques, i.e., Physical Unclonable Function (PUF) and blockchain. In detail, PUF can generate multiple Challenge-Response Pairs (CRPs) for IIoT devices by leveraging their unique physical features. Moreover, blockchain platforms are employed for storing/synchronizing CRPs, thereby resisting the single-point-failure. Although realizing the unclonable authentications, the existing works ignore the device heterogeneity of IIoT and fail to develop the specified blockchain platform for supporting PUF. In this article, we present a Hybrid PUF-based consortium blockchain for IIoT authentication, named HPCchain. Specifically, we first present the notion of Hybrid-PUF, which assigns different devices to generate different types of PUFs, and then employs them to play different roles in HPCchain. In this way, we can overcome the IIoT heterogeneity. Moreover, we propose the PUF-empowered credit scheme for HPCchain and realize the dynamic endorsement, with which we develop a PUF-based consensus mechanism for HPCchain. Finally, we design the registration and authentication schemes for IIoT nodes, atop HPCchain. Extensive experiments demonstrate the validity of our proposals.

We study stochastic gradient descent (SGD) with local iterations in the presence of Byzantine clients, motivated by federated learning. The clients, instead of communicating with the server in every iteration, maintain their local models, which they update by taking several SGD iterations based on their own datasets and then communicate the net update with the server, thereby achieving communication efficiency. Furthermore, only a subset of clients communicates with the server at synchronization times. The Byzantine clients may collude and send arbitrary vectors to the server to disrupt the learning process. To combat the adversary, we employ an efficient high-dimensional robust mean estimation algorithm at the server to filter-out corrupt vectors; and to analyze the outlier-filtering procedure, we develop a novel matrix concentration result that may be of independent interest. We provide convergence analyses for both strongly-convex and non-convex smooth objectives in the heterogeneous data setting. We believe that ours is the first Byzantine-resilient local SGD algorithm and analysis with non-trivial guarantees.We corroborate our theoretical results with experiments for neural network training.

The integration of intramuscular fat-or marbling-into cultured meat will be critical for meat texture, mouthfeel, flavor, and thus consumer appeal. However, culturing muscle tissue with marbling is challenging since myocytes and adipocytes have different media and scaffold requirements for optimal growth and differentiation. Here, we present an approach to engineer multicomponent tissue using myogenic and adipogenic microtissues. The key innovation in our approach is the engineering of myogenic and adipogenic microtissues using scaffolds with customized physical properties; we use these microtissues as building blocks that spontaneously adhere to produce multicomponent tissue, or marbled cultured meat. Myocytes are grown and differentiated on gelatin nanofiber scaffolds with aligned topology that mimic the aligned structure of skeletal muscle and promotes the formation of myotubes in both primary rabbit skeletal muscle and murine C2C12 cells. Pre-adipocytes are cultured and differentiated on edible gelatin microbead scaffolds, which are customized to have a physiologically-relevant stiffness, and promote lipid accumulation in both primary rabbit and murine 3T3-L1 pre-adipocytes. After harvesting and stacking the individual myogenic and adipogenic microtissues, we find that the resultant multicomponent tissues adhere into intact structures within 6-12 h in culture. The resultant multicomponent 3D tissue constructs show behavior of a solid material with a Young's modulus of ~ 2 ± 0.4 kPa and an ultimate tensile strength of ~ 23 ± 7 kPa without the use of additional crosslinkers. Using this approach, we generate marbled cultured meat with ~ mm to ~ cm thickness, which has a protein content of ~ 4 ± 2 g/100 g that is comparable to a conventionally produced Wagyu steak with a protein content of ~ 9 ± 4 g/ 100 g. We show the translatability of this layer-by-layer assembly approach for microtissues across primary rabbit cells, murine cell lines, as well as for gelatin and plant-based scaffolds, which demonstrates a strategy to generate edible marbled meats derived from different species and scaffold materials.

We present empirical conductance relations that are derived from incoherent scatter radar observations and correlated with all sky imager observations to identify the morphology of the aurora. We use 75461 events collected using the Poker Flat Incoherent Scatter Radar (PFISR) with associated all sky imagers observations spanning the years 2012–2016. In addition to classifying these events based on auroral morphology, we estimated the Hall and Pedersen conductance and the differential number flux from which the energy flux and the average energy can be calculated. The differential number flux was estimated using the maximum entropy inversion method described in Semeter and Kamalabadi (2005), but now incorporating the Fang et al. (2010) ionization model. The main results of this investigation are the power law equations that describe the median, 90th, and 10th percentile Hall and Pedersen conductance as a function of energy flux and average energy. These power law fits are performed for different auroral morphology including all events, discrete, diffuse, and pulsating auroral events. The median Pedersen conductance is found to be in good agreement with past empirical conductance specifications by Robinson et al. (1987); however, the median Hall conductance from the PFISR observations is found to be larger than the empirical Hall conductance formulas by Robinson et al. (1987). Pulsating aurora is found to be the most frequently occurring auroral morphology. Furthermore, pulsating aurora has an important contribution to Hall conductance since it has higher average energies than discrete aurora. The results from this investigation are applicable to space weather models and may enable better agreement between model‐data comparisons. This article is protected by copyright. All rights reserved.

In this paper we study the regularity property of Hele-Shaw flow, where source and drift are present in the evolution. More specifically we consider H\"{o}lder continuous source and Lipschitz continuous drift. We show that if the free boundary of the solution is locally close to a Lipschitz graph, then it is indeed Lipschitz, given that the Lipschitz constant is small. When there is no drift, our result establishes $C^{1,\gamma}$ regularity of the free boundary by combining our result with the obstacle problem theory. In general, when the source and drift are both smooth, we prove that the solution is non-degenerate, indicating higher regularity of the free boundary.

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed regeneration of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing to identify neuronal subpopulations that restore walking after incomplete SCI. We show that chemoattracting and guiding the transected axons of these neurons to their natural target region led to substantial recovery of walking after complete SCI in mice, whereas regeneration of axons simply across the lesion had no effect. Thus, reestablishing the natural projections of characterized neurons forms an essential part of axon regeneration strategies aimed at restoring lost neurological functions.

We examined longitudinal changes in BMD among women in the mid-life starting metformin. Study subjects were 57 years old (mean), and 36% were White. Women initiating metformin were similar to noninitiators. During the 3-year follow-up, BMD loss at all anatomic areas was similar between groups and in subgroups including baseline fasting blood glucose. Women with type 2 diabetes have higher bone mineral density (BMD), experience slower BMD loss, but have increased fracture risk. Data regarding the effect of metformin on BMD remain discordant. We examined longitudinal changes in BMD among women in the mid-life starting metformin. Participants in the Study of Women’s Health Across the Nation (SWAN), a diverse community-based US cohort, with BMD measurements were evaluated. Propensity score matching helped balance baseline characteristics of metformin initiators versus noninitiators. Mixed model regression tested the change in BMD between groups. Subjects (n = 248) were 57.4 years old (mean), and 35.9% were White. Women initiating metformin (n = 124) were similar to noninitiators (n = 124) in age and race/ethnicity. During the median 3-year follow-up, BMD loss at all anatomic areas was similar between the metformin initiators and nonusers (all p > 0.3). Subgroup analyses including baseline fasting blood glucose showed no between-group differences. Initiation of metformin (vs. not) in peri-menopausal women was not associated with BMD changes. Women in the mid-life starting metformin had longitudinal changes in BMD very similar to other women not starting metformin.

A predictive model for the variation of ionospheric currents is of great scientific and practical importance to our modern industrial society. To study the response of ionospheric currents to external drivers including geomagnetic indices and solar radiation, we developed a feedforward neural network model trained on the Equivalent Ionospheric Current (EIC) data from 1st January 2007 to 31st December 2019. Due to the highly imbalanced nature of the ionospheric currents data, which means that the data of extreme events are much less than those of quiet times, we utilized different loss functions to improve the model performance. Our model demonstrates the potential to predict the active events of ionospheric currents reasonably well (e.g., EICs during substorms) within a timescale of a few minutes. Although the data used for training are measurements over the North American and Greenland sectors, our model is not only able to predict EICs within this region, but is also able to provide a promising out‐of‐sample prediction on a global scale.

How does a single amino acid mutation occurring in the blinding disease, Leber’s hereditary optic neuropathy (LHON), impair electron shuttling in mitochondria? We investigated changes induced by the m.3460 G>A mutation in mitochondrial protein ND1 using the tools of Molecular Dynamics and Free Energy Perturbation simulations, with the goal of determining the mechanism by which this mutation affects mitochondrial function. A recent analysis suggested that the mutation’s replacement of alanine A52 with a threonine perturbs the stability of a region where binding of the electron shuttling protein, Coenzyme Q10, occurs. We found two functionally opposing changes involving the role of Coenzyme Q10. The first showed that quantum electron transfer from the terminal Fe/S complex, N2, to the Coenzyme Q10 headgroup, docked in its binding pocket, is enhanced. However, this positive adjustment is overshadowed by our finding that the mobility of Coenzyme Q10 in its oxidized and reduced states, entering and exiting its binding pocket, is disrupted by the mutation in a manner that leads to conditions promoting the generation of reactive oxygen species. An increase in reactive oxygen species caused by the LHON mutation has been proposed to be responsible for this optic neuropathy.

Background Hypoglycemia from overtreatment is a serious but underrecognized complication among older adults with type 2 diabetes. However, diabetes treatment is seldom deintensified. We assessed the effectiveness of a Clinical Decision Support (CDS) tool and shared decision‐making (SDM) in decreasing the number of patients at risk for hypoglycemia and reducing the impact of non‐severe hypoglycemic events. Methods HypoPrevent was a pre‐post, single arm study at a five‐site primary care practice. We identified at‐risk patients (≥65 years‐old, with type 2 diabetes, treated with insulin or sulfonylureas, and HbA 1c < 7.0%). During three clinic visits over 6 months, clinicians used the CDS tool and SDM to assess hypoglycemic risk, set individualized HbA 1c goals, and adjust use of hypoglycemic agents. We assessed the number of patients setting individualized HbA 1c goals or modifying medication use, changes in the population at risk for hypoglycemia, and changes in impact of non‐severe hypoglycemic events using a validated patient‐reported outcome tool (TRIM‐HYPO). Results We enrolled 94 patients (mean age—74; mean HbA 1c (±SD)—6.36% ± 0.43), of whom 94% set an individualized HbA 1c goal at either the baseline or first follow‐up visit. Ninety patients completed the study. Insulin or sulfonylurea use was decreased or eliminated in 20%. An HbA 1c level before and after goal setting was obtained in 53% ( N = 50). Among these patients, the mean HbA 1c increased 0.53% ( p < 0.0001) and the number of patients at‐risk decreased by 46% ( p < 0.0001). Statistically significant reductions in the impact of hypoglycemia during daily activities occurred in both the total score and each functional domain of TRIM‐HYPO. Conclusions In a population of older patients at risk for hypoglycemia, the use of a CDS tool and SDM reduced the population at risk and decreased the use of insulin and sulfonylureas. Using a patient‐reported outcome tool, we demonstrated significant reductions in the impact of hypoglycemia on daily life.

Objective To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA). Methods We systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021, for randomised trials of pharmacological interventions for people with hand OA. Two reviewers independently extracted study data and assessed the risk of bias. We calculated the effect sizes for pain (standardised mean differences) using Bayesian random effects models for network meta-analysis (NMA) and pairwise meta-analysis. Based on a pre-specified protocol, we prospectively registered the study at PROSPERO, CRD42021215393. Results We included 72 trials with 7609 participants. 65 trials (n=5957) were eligible for the quantitative synthesis, investigating 29 pharmacological interventions. Oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids’ NMA effect sizes were −0.18 (95% credible interval −0.36 to 0.02) and −0.54 (−0.83 to −0.24), respectively, compared with placebo, and the result was consistent when limiting evidence to the pairwise meta-analysis of trials without high risk of bias. Intra-articular hyaluronate, intra-articular glucocorticoids, hydroxychloroquine, and topical NSAIDs’ NMA effect sizes were 0.22 (−0.08 to 0.51), 0.25 (0.00 to 0.51), −0.01 (−0.19 to 0.18), and −0.14 (−0.33 to 0.08), respectively, compared with placebo. Oral NSAIDs were inferior to oral glucocorticoids with an NMA effect size of 0.36 (0.01 to 0.72). No intervention was superior to placebo when stratifying for thumb and finger OA. Conclusion Oral NSAIDs and glucocorticoids are apparently effective pharmacological interventions in hand OA. Intra-articular therapies and topical NSAIDs were not superior to placebo.

In modern optics, materials with large birefringence (Δ n , where n is the refractive index) are sought after for polarization control (e.g., in wave plates, polarizing beam splitters, etc. [ 3 ] ), nonlinear optics and quantum optics (e.g., for phase matching [ 5 ] and production of entangled photons [ 6 ] ), micromanipulation, [ 7 ] and as a platform for unconventional light‐matter coupling, such as Dyakonov‐like surface polaritons [ 8 ] and hyperbolic phonon polaritons. [ 11 ] Layered “van der Waals” materials, with strong intra‐layer bonding and weak inter‐layer bonding, can feature some of the largest optical anisotropy [ 16 ] ; however, their use in most optical systems is limited because their optic axis is out of the plane of the layers and the layers are weakly attached, making the anisotropy hard to access. Here, we demonstrate that a bulk crystal with subtle periodic modulations in its structure — Sr9/8TiS3 — is transparent and positive‐uniaxial, with extraordinary index n e = 4.5 and ordinary index n o = 2.4 in the mid‐ to far‐infrared. The excess Sr, compared to stoichiometric SrTiS3, results in the formation of TiS6 trigonal‐prismatic units that break the infinite chains of face‐shared TiS6 octahedra in SrTiS3 into periodic blocks of five TiS6 octahedral units. The additional electrons introduced by the excess Sr subsequently occupy the TiS6 octahedral blocks to form highly oriented and polarizable electron clouds, which selectively boost the extraordinary index n e and result in record birefringence (Δ n > 2.1 with low loss). The connection between subtle structural modulations and large changes in refractive index suggests new categories of anisotropic materials and also tunable optical materials with large refractive‐index modulation and low optical losses. This article is protected by copyright. All rights reserved

Background Obesity is a major threat to public health and traditional bariatric surgery continues to have low utilization. Endoscopic treatments for obesity have emerged that offer less risk, but questions remain regarding efficacy, durability, and safety. We compared the efficacy of endoscopic bariatric procedures as compared to other existing treatments. Methods A literature search of Embase, Cochrane Central, and Pubmed was conducted from January 1, 2014 to December 7, 2021, including endoscopic bariatric therapies that were FDA or CE approved at the time of search to non-endoscopic treatments. Thirty-seven studies involving 15,639 patients were included. Primary outcomes included % total body weight loss (%TBWL), % excess body weight loss (%EBWL), and adverse events. Secondary outcomes included quality of life data and differences in hemoglobin A1C levels. Strength of clinical trial and observational data were graded according to the Cochrane methods. Results Intragastric balloons achieved greater %TBWL with a range of 7.6–14.1% compared to 3.3–6.7% with lifestyle modification at 6 months, and 7.5–14.0% compared to 3.1–7.9%, respectively, at 12 months. When endoscopic sleeve gastroplasty (ESG) was compared to laparoscopic sleeve gastrectomy (LSG), ESG had less %TBWL at 4.7–14.4% compared to 18.8–26.5% after LSG at 6 months, and 4.5–18.6% as compared to 28.4–29.3%, respectively, at 12 months. For the AspireAssist, there was greater %TBWL with aspiration therapy compared to lifestyle modification at 12 months, 12.1–18.3% TBWL versus 3.5–5.9% TBWL, respectively. All endoscopic interventions had higher adverse events rates compared to lifestyle modification. Conclusion This review is the first to evaluate various endoscopic bariatric therapies using only RCTs and observational studies for evaluation of weight loss compared with conservative management, lifestyle modification, and bariatric surgery. Endoscopic therapies result in greater weight loss compared to lifestyle modification, but not as much as bariatric surgery. Endoscopic therapies may be beneficial as an alternative to bariatric surgery.

Despite recent approvals of lifesaving treatments for chronic lymphocytic leukemia (CLL), real-world data on the tolerability of the Bruton tyrosine kinase inhibitor ibrutinib for CLL treatment are lacking, especially in Black patients. To expand upon a previously reported retrospective chart review of ibrutinib-treated patients with CLL to increase the number of sites and the enrollment period in first-line (1L) and relapsed/refractory (R/R) settings with a subanalysis based on ethnicity. Adults with CLL who initiated ibrutinib treatment from five centers were followed for ≥ 6 months. We identified 482 patients with CLL [405 White (153 1L, 252 R/R), 37 Black (17 1L, 20 R/R), 40 other/unidentified]. At baseline, 58.5% of all patients (68.8% of Black patients) had hypertension. At a median follow-up of 28.2 months, 31.1% of patients overall discontinued ibrutinib, 16.2% due to adverse events (12.2% 1L, 18.8% R/R). Overall, 46.0% of patients experienced ≥ 1 dose hold (40.2% 1L, 49.8% R/R), and 28.8% of patients experienced ≥ 1 dose reduction (24.9% 1L, 31.4% R/R). Among Black patients, ibrutinib was discontinued in 24.3% of patients (17.6% 1L, 30.0% R/R), 8.1% due to disease progression and 5.4% due to adverse events; 40.5% of patients experienced ≥ 1 dose hold (35.3% 1L, 45.0% R/R), and 32.4% of patients experienced ≥ 1 dose reduction (23.5% 1L, 40.0% R/R). Toxicity and disease progression were the most common reasons for ibrutinib discontinuations in the overall population and among Black patients, respectively. Encouraging research participation of underrepresented patient groups will help clinicians better understand treatment outcomes.