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In this paper we argue for a fractally recursive model of (non)standard Cantonese to account for the indexicalities of language use associated with “new immigrants” and the complex indexical fields at work in Hong Kong. Our empirical data come from a Hong Kong noodle shop's social media advertisement, its use and enregisterment of a way of speaking associated with female migrants of a lower socioeconomic status from mainland China, and viewers' online reactions to this. We demonstrate that the viewers evaluate this mediatised “new immigrant” Cantonese as indexical of both standardness and non-standardness, of locality, outsiderness and national power - all depending upon the scalar perspective they take within a fractally recursive system.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

Background Social distancing is a crucial intervention to slow down person-to-person transmission of COVID-19. However, social distancing has negative consequences, including increases in depression and anxiety. Digital interventions, such as text messaging, can provide accessible support on a population-wide scale. We developed text messages in English and Spanish to help individuals manage their depressive mood and anxiety during the COVID-19 pandemic. Objective In a two-arm randomized controlled trial, we aim to examine the effect of our 60-day text messaging intervention. Additionally, we aim to assess whether the use of machine learning to adapt the messaging frequency and content improves the effectiveness of the intervention. Finally, we will examine the differences in daily mood ratings between the message categories and time windows. Methods The messages were designed within two different categories: behavioral activation and coping skills. Participants will be randomized into (1) a random messaging arm, where message category and timing will be chosen with equal probabilities, and (2) a reinforcement learning arm, with a learned decision mechanism for choosing the messages. Participants in both arms will receive one message per day within three different time windows and will be asked to provide their mood rating 3 hours later. We will compare self-reported daily mood ratings; self-reported depression, using the 8-item Patient Health Questionnaire; and self-reported anxiety, using the 7-item Generalized Anxiety Disorder scale at baseline and at intervention completion. Results The Committee for the Protection of Human Subjects at the University of California Berkeley approved this study in April 2020 (No. 2020-04-13162). Data collection began in April 2020 and will run to April 2021. As of August 24, 2020, we have enrolled 229 participants. We plan to submit manuscripts describing the main results of the trial and results from the microrandomized trial for publication in peer-reviewed journals and for presentations at national and international scientific meetings. Conclusions Results will contribute to our knowledge of effective psychological tools to alleviate the negative effects of social distancing and the benefit of using machine learning to personalize digital mental health interventions. Trial Registration ClinicalTrials.gov NCT04473599; https://clinicaltrials.gov/ct2/show/NCT04473599 International Registered Report Identifier (IRRID) DERR1-10.2196/23592

BACKGROUND Social distancing is a crucial intervention to slow down person-to-person transmission of COVID-19. However, social distancing has negative consequences, including increases in depression and anxiety. Digital interventions, such as text messaging, can provide accessible support on a population-wide scale. We developed text messages in English and Spanish to help individuals manage their depressive mood and anxiety during the COVID-19 pandemic. OBJECTIVE In a two-arm randomized controlled trial, we aim to examine the effect of our 60-day text messaging intervention. Additionally, we aim to assess whether the use of machine learning to adapt the messaging frequency and content improves the effectiveness of the intervention. Finally, we will examine the differences in daily mood ratings between the message categories and time windows. METHODS The messages were designed within two different categories: behavioral activation and coping skills. Participants will be randomized into (1) a random messaging arm, where message category and timing will be chosen with equal probabilities, and (2) a reinforcement learning arm, with a learned decision mechanism for choosing the messages. Participants in both arms will receive one message per day within three different time windows and will be asked to provide their mood rating 3 hours later. We will compare self-reported daily mood ratings; self-reported depression, using the 8-item Patient Health Questionnaire; and self-reported anxiety, using the 7-item Generalized Anxiety Disorder scale at baseline and at intervention completion. RESULTS The Committee for the Protection of Human Subjects at the University of California Berkeley approved this study in April 2020 (No. 2020-04-13162). Data collection began in April 2020 and will run to April 2021. As of August 24, 2020, we have enrolled 229 participants. We plan to submit manuscripts describing the main results of the trial and results from the microrandomized trial for publication in peer-reviewed journals and for presentations at national and international scientific meetings. CONCLUSIONS Results will contribute to our knowledge of effective psychological tools to alleviate the negative effects of social distancing and the benefit of using machine learning to personalize digital mental health interventions. CLINICALTRIAL ClinicalTrials.gov NCT04473599; https://clinicaltrials.gov/ct2/show/NCT04473599 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/23592

BACKGROUND: Spontaneous breathing trials (SBTs) and daily sedation interruptions (DSIs) reduce both the duration of mechanical ventilation and ICU length of stay (LOS). The impact of these practices in patients with ARDS has not previously been reported. We examined whether implementation of SBT/DSI protocols reduce duration of mechanical ventilation and ICU LOS in a retrospective group of subjects with ARDS at a large, urban, level-1 trauma center. METHODS: All ARDS survivors from 2002 to 2016 (N = 1,053) were partitioned into 2 groups: 397 in the pre-SBT/DSI group (June 2002–December 2007) and 656 in the post-SBT/DSI group (January 2009–April 2016). Patients from 2008, during the protocol implementation period, were excluded. An additional SBT protocol database (2008–2010) was used to assess the efficacy of SBT in transitioning subjects with ARDS to unassisted breathing. Comparisons were assessed by either unpaired t tests or Mann-Whitney tests. Multiple comparisons were made using either one-way analysis of variance or Kruskal-Wallis and Dunn9s tests. Linear regression modeling was used to determine variables independently associated with mechanical ventilation duration and ICU LOS; differences were considered statistically significant when P RESULTS: Compared to the pre-protocol group, subjects with ARDS managed with SBT/DSI protocols experienced pronounced reductions both in median (IQR) mechanical ventilation duration (14 [6–29] vs 9 [4–17] d, respectively, P CONCLUSION: Evidenced-based protocols governing weaning and sedation practices were associated with both reduced mechanical ventilation duration and ICU LOS in subjects with ARDS. However, higher respiratory system compliance in the SBT/DSI cohort also contributed to these improved outcomes.

BACKGROUND: ARDS is characterized by decreased functional residual capacity (FRC), heterogeneous lung injury, and severe hypoxemia. Tidal ventilation is preferentially distributed to ventilated alveoli. Aerosolized prostaglandin I2 exploits this pathophysiology by inducing local vasodilation, thereby increasing ventilation-perfusion matching and reducing hypoxemia. Therefore, aerosolized prostaglandin I2 efficacy may depend upon FRC. Both PaO2/FIO2 and compliance of the respiratory system (CRS) are indirect signifiers of FRC and thus may partly determine the response to aerosolized prostaglandin I2. METHODS: We reviewed the records of 208 ARDS subjects who received aerosolized prostaglandin I2 and had arterial blood gases done before and after the initiation of therapy, without other ventilator manipulations. Subjects were grouped according to baseline PaO2/FIO2 (lowest: 90 mm Hg) and CRS ( RESULTS: Mean PaO2/FIO2 increased by 33 mm Hg (42%) upon initiation of prostaglandin I2, with a responder rate of 62%. PaO2/FIO2 increased significantly in all oxygenation groups. The highest baseline PaO2/FIO2 group had the greatest improvement and responder rate (51 ± 63 mm Hg, and 82%). In addition, those with sepsis had a smaller improvement in PaO2/FIO2 compared with those without sepsis (18 ± 35 vs 40 ± 55 mm Hg, P = .002). Both PaO2/FIO2 and responder rate increased as CRS improved, but between-group improvements were not as consistent. In the final model, the only factors that predicted a positive response to aerosolized prostaglandin I2 were baseline PaO2/FIO2 (odds ratio 1.10 [1.004–1.205], P = .042) and CRS (odds ratio 1.04 [1.01–1.08], P = .02). CONCLUSIONS: Aerosolized prostaglandin I2 improves oxygenation in approximately 60% of ARDS cases. A favorable response was most strongly associated with baseline PaO2/FIO2 and CRS.

Negligible solubility of curcumin in water combined with rapid degradation have limited its medical applications. In this contribution, eutectic mixture of curcumin with one of its degradation products (ferulic acid) was encapsulated into long and medium chain triglycerides oils and stabilised by the non-ionic surfactant polyoxyethylene oleyl ether Brij® O10 (C18:1E10) and bile acid derivative (sodium deoxycholate). Thermal and spectroscopic analysis confirmed the presence of curcumin as solid nanocrystals embedded within the microemulsion droplets. UV-spectroscopy and LC-MS studies of formed microemulsions revealed that degradation of curcumin in water was significantly reduced with more than 83% of curcumin remained intact after 24 h 1H NMR results showed that curcumin remained stable upon heating in the range between 297K and 327 K with no signs of degradation to ferulic acid. The results showed solubility enhancement of curcumin with a range of 3–5 mg/mL. NF-κB reporter cell assay revealed low cytotoxicity and three folds stronger anti-inflammatory potential compared to curcumin. Microemulsions remained stable for over 12 months with extended stability of formulations that contained curcumin/ferulic acid in glyceryl tricaprate based microemulsions. Overall these results suggest novel role for particle engineering via using ferulic acid as stability and activity enhancer for curcumin through free radicals scavenging mechanism.

Background aims The aim was to evaluate cartilage regeneration in animal models involving induced knee joint damage. Through cell-mediated gene therapy methods, a cell mixture comprising a 3:1 ratio of genetically unmodified human chondrocytes and transforming growth factor beta-1 (TGF-β1)-secreting human chondrocytes (TG-C), generated via retroviral transduction, resulted in successful cartilage proliferation in damaged regions. Methods Non-clinical toxicology assessments for efficacy, biodistribution and local/systemic toxicity of single intra-articular administration of the cell mixture in mice, rabbits and goats was conducted. Results Administration of the mixture was tolerated well in all of the species. There was evidence of cartilage proliferation in rabbits and goats. As an additional precautionary step, the efficacy of TGF-β1 secretion in irradiated human chondrocytes was also demonstrated. Conclusions Four studies in rabbits and goats demonstrated the safety and efficacy of TG-C following direct intra-articular administration in animal models involving induced knee joint damage. Based on these pre-clinical studies authorization has been received from the USA Food and Drug Administration (FDA) to proceed with an initial phase I clinical study of TG-C for degenerative arthritis.

Bone morphogenetic protein 2 (BMP2) was selected as a transgene to regenerate osteoporotic bone defects after several BMPs were tested using a bone formation study in nude mice. Human chondrocytes were transduced with a BMP2-containing retroviral vector, and single clones were selected. The cells were characterized over numerous passages for growth and BMP2 expression. The single clones were irradiated and tested for viability. BMP2 expression lasted for 3 weeks before dying off completely after approximately 1 month. Irradiated and non-irradiated transduced chondrocytes successfully healed fractures in osteoporotic rats induced by ovariectomy. The osteoinducing effect of irradiated cells was better than that of their non-irradiated counterparts or a chondrocytes-only control. This study showed that delivering BMP2 from the transduced and irradiated chondrocytes could be an effective and safe method of repairing osteoporotic bone fractures.

One of the most important factors in the production of cartilage is transforming growth factor beta1 (TGF-beta1). To obtain sustained release of TGF-beta1, a cell-mediated gene therapy technique was introduced. We infected chondrocytes with a retroviral vector carrying the TGF-beta1 gene. The single clone derivative showed sustained TGF-beta1 secretion. It also showed constitutive type II collagen expression. Whereas the TGF-beta1 protein itself is unable to induce formation of cartilage in vivo, human chondrocytes engineered to express a retroviral vector encoding TGF-beta1 showed cartilage formation in vivo when cells were injected into nude mice intradermally. These data suggest that cell-mediated gene therapy using TGF-beta1 as a transgene would be a promising treatment for osteoarthritis.

Retroviral vectors have been widely used in gene therapy due to their simple genomic structure and high transduction efficiency. We previously reported a construction of Moloney murine sarcoma virus (MoMSV) and Moloney murine leukemia virus (MoMLV) hybrid-based retroviral vectors with significantly improved efficiency of transgene expression after stable incorporation into the host genome. In these vectors, contain no coding sequence for the gag, pol, or env gene that can be used for homologous recombination with sequences introduced in the packaging system for a recombination competent retroviruses (RCR) generation.