Simulation of optoelectronic oscillator injection locking, pulling & spiking phenomena.

Complex envelope and reduced phase simulation models describing the dynamical behaviour of an optoelectronic oscillator (OEO) under injection by an external source are described. The models build on the foundations of a previously reported delay integral/differential equation (DDE) theory of injection locking of time delay oscillators (TDO) such as the OEO. The DDE formulation is particularly amenable to high precision simulation using the Simulink™ block diagram environment. The correspondence between the blocks and the oscillator components offers intuition and considerable freedom to explore different circuit architectures and design variations with minimal coding effort. The simulations facilitate the study of the profound effect the multimode nature of a TDO has on its dynamical behavior. The reduced phase models that make use of the Leeson approximation are generally successful in reproducing the results of complex envelope models for established oscillations except for spiking phenomena for which the Leeson approximation fails. Simulation results demonstrating phenomena not captured by classical injection theory are presented, including multimode oscillation, the appearance of sidemodes in the RF and phase noise spectrum, and persistent spike trains redolent of recent experimental observations of [Formula: see text] phase pulse trains in a broadband OEO under injection.

Effects of Cognitive Behavioral Therapy and Cash Transfers on Older Persons Living Alone in India : A Randomized Trial.

BACKGROUND: A growing number of older persons in developing countries live entirely alone and are physically, mentally, and financially vulnerable. OBJECTIVE: To determine whether phone-based cognitive behavioral therapy (CBT) or a cash transfer reduce functional impairment, depression, or food insecurity in this population. DESIGN: Randomized controlled trial. (ClinicalTrials.gov: NCT04225845; American Economic Association RCT Registry: AEARCTR-0007582). SETTING: Tamil Nadu, India, 2021. PARTICIPANTS: 1120 people aged 55 years and older and living alone. INTERVENTIONS: A 6-week, phone-based CBT and a 1-time cash transfer of 1000 rupees (U.S. $12 at market exchange rates) were evaluated in a factorial design. MEASUREMENTS: The World Health Organization Disability Assessment Schedule (WHODAS), the Geriatric Depression Scale, and food security, all measured 3 weeks after CBT for 977 people and 3 months after for 932. Surveyors were blind to treatment assignment. RESULTS: The WHODAS score (scale 0 to 48, greater values representing more impairment) decreased between baseline and the 3-week follow-up by 2.92 more (95% CI, -5.60 to -0.23) in the group assigned cash only than in the control group, and the depression score (ranging from 0 to 15, higher score indicating more depressive symptoms) decreased by 1.01 more (CI, -2.07 to 0.06). These effects did not persist to the 3-month follow-up, and CBT alone and the 2 together had no significant effects. There were no effects on food security. LIMITATIONS: The study cannot say whether more sustained or in-person therapy would have been effective, how results would translate outside of the COVID-19 period, or whether results in the consented sample differ from those in a larger population. Primary outcomes were self-reported. CONCLUSION: Among older people living alone, a small cash transfer was effective in alleviating short-term (3 weeks) functional impairment, produced a small but not clinically or statistically significant reduction in depression, and had no effect on food security. There were no short-term effects from CBT or the 2 interventions together. None of the interventions showed any effect at 3 months. PRIMARY FUNDING SOURCE: National Institute on Aging (NIA).

Effects of a large-scale social media advertising campaign on holiday travel and COVID-19 infections: a cluster randomized controlled trial.

During the Coronavirus Disease 2019 (COVID-19) epidemic, many health professionals used social media to promote preventative health behaviors. We conducted a randomized controlled trial of the effect of a Facebook advertising campaign consisting of short videos recorded by doctors and nurses to encourage users to stay at home for the Thanksgiving and Christmas holidays ( NCT04644328 and AEARCTR-0006821 ). We randomly assigned counties to high intensity (n = 410 (386) at Thanksgiving (Christmas)) or low intensity (n = 410 (381)). The intervention was delivered to a large fraction of Facebook subscribers in 75% and 25% of randomly assigned zip codes in high- and low-intensity counties, respectively. In total, 6,998 (6,716) zip codes were included, and 11,954,109 (23,302,290) users were reached at Thanksgiving (Christmas). The first two primary outcomes were holiday travel and fraction leaving home, both measured using mobile phone location data of Facebook users. Average distance traveled in high-intensity counties decreased by -0.993 percentage points (95% confidence interval (CI): -1.616, -0.371; P = 0.002) for the 3 days before each holiday compared to low-intensity counties. The fraction of people who left home on the holiday was not significantly affected (adjusted difference: 0.030; 95% CI: -0.361, 0.420; P = 0.881). The third primary outcome was COVID-19 infections recorded at the zip code level in the 2-week period starting 5 days after the holiday. Infections declined by 3.5% (adjusted 95% CI: -6.2%, -0.7%; P = 0.013) in intervention compared to control zip codes. Social media messages recorded by health professionals before the winter holidays in the United States led to a significant reduction in holiday travel and subsequent COVID-19 infections.

Effect of Physician-Delivered COVID-19 Public Health Messages and Messages Acknowledging Racial Inequity on Black and White Adults' Knowledge, Beliefs, and Practices Related to COVID-19: A Randomized Clinical Trial.

Importance: Social distancing is critical to the control of COVID-19, which has disproportionately affected the Black community. Physician-delivered messages may increase adherence to these behaviors. Objectives: To determine whether messages delivered by physicians improve COVID-19 knowledge and preventive behaviors and to assess the differential effectiveness of messages tailored to the Black community. Design, Setting, and Participants: This randomized clinical trial of self-identified White and Black adults with less than a college education was conducted from August 7 to September 6, 2020. Of 44 743 volunteers screened, 30 174 were eligible, 5534 did not consent or failed attention checks, and 4163 left the survey before randomization. The final sample had 20 460 individuals (participation rate, 68%). Participants were randomly assigned to receive video messages on COVID-19 or other health topics. Interventions: Participants saw video messages delivered either by a Black or a White study physician. In the control groups, participants saw 3 placebo videos with generic health topics. In the treatment group, they saw 3 videos on COVID-19, recorded by several physicians of varied age, gender, and race. Video 1 discussed common symptoms. Video 2 highlighted case numbers; in one group, the unequal burden of the disease by race was discussed. Video 3 described US Centers for Disease Control and Prevention social distancing guidelines. Participants in both the control and intervention groups were also randomly assigned to see 1 of 2 American Medical Association statements, one on structural racism and the other on drug price transparency. Main Outcomes and Measures: Knowledge, beliefs, and practices related to COVID-19, demand for information, willingness to pay for masks, and self-reported behavior. Results: Overall, 18 223 participants (9168 Black; 9055 White) completed the survey (9980 [55.9%] women, mean [SD] age, 40.2 [17.8] years). Overall, 6303 Black participants (34.6%) and 7842 White participants (43.0%) were assigned to the intervention group, and 1576 Black participants (8.6%) and 1968 White participants (10.8%) were assigned to the control group. Compared with the control group, the intervention group had smaller gaps in COVID-19 knowledge (incidence rate ratio [IRR], 0.89 [95% CI, 0.87-0.91]) and greater demand for COVID-19 information (IRR, 1.05 [95% CI, 1.01-1.11]), willingness to pay for a mask (difference, $0.50 [95% CI, $0.15-$0.85]). Self-reported safety behavior improved, although the difference was not statistically significant (IRR, 0.96 [95% CI, 0.92-1.01]; P = .08). Effects did not differ by race (F = 0.0112; P > .99) or in different intervention groups (F = 0.324; P > .99). Conclusions and Relevance: In this study, a physician messaging campaign was effective in increasing COVID-19 knowledge, information-seeking, and self-reported protective behaviors among diverse groups. Studies implemented at scale are needed to confirm clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04502056.

Doctors' and Nurses' Social Media Ads Reduced Holiday Travel and COVID-19 infections: A cluster randomized controlled trial in 13 States.

During the COVID-19 epidemic, many health professionals started using mass communication on social media to relay critical information and persuade individuals to adopt preventative health behaviors. Our group of clinicians and nurses developed and recorded short video messages to encourage viewers to stay home for the Thanksgiving and Christmas Holidays. We then conducted a two-stage clustered randomized controlled trial in 820 counties (covering 13 States) in the United States of a large-scale Facebook ad campaign disseminating these messages. In the first level of randomization, we randomly divided the counties into two groups: high intensity and low intensity. In the second level, we randomly assigned zip codes to either treatment or control such that 75% of zip codes in high intensity counties received the treatment, while 25% of zip codes in low intensity counties received the treatment. In each treated zip code, we sent the ad to as many Facebook subscribers as possible (11,954,109 users received at least one ad at Thanksgiving and 23,302,290 users received at least one ad at Christmas). The first primary outcome was aggregate holiday travel, measured using mobile phone location data, available at the county level: we find that average distance travelled in high-intensity counties decreased by -0.993 percentage points (95% CI -1.616, -0.371, p -value 0.002) the three days before each holiday. The second primary outcome was COVID-19 infection at the zip-code level: COVID-19 infections recorded in the two-week period starting five days post-holiday declined by 3.5 percent (adjusted 95% CI [-6.2 percent, -0.7 percent], p -value 0.013) in intervention zip codes compared to control zip codes. ONE SENTENCE SUMMARY: In a large scale clustered randomized controlled trial, short messages recorded by health professionals before the winter holidays in the United States and sent as ads to social media users led to a significant reduction in holiday travel, and to a decrease in subsequent COVID-19 infection at the population level.

Doctors and Nurses Social Media Ads Reduced Holiday Travel and COVID-19 infections: A cluster randomized controlled trial in 13 States.

During the COVID-19 epidemic, many health professionals started using mass communication on social media to relay critical information and persuade individuals to adopt preventative health behaviors. Our group of clinicians and nurses developed and recorded short video messages to encourage viewers to stay home for the Thanksgiving and Christmas Holidays. We then conducted a two-stage clustered randomized controlled trial in 820 counties (covering 13 States) in the United States of a large-scale Facebook ad campaign disseminating these messages. In the first level of randomization, we randomly divided the counties into two groups: high intensity and low intensity. In the second level, we randomly assigned zip codes to either treatment or control such that 75% of zip codes in high intensity counties received the treatment, while 25% of zip codes in low intensity counties received the treatment. In each treated zip code, we sent the ad to as many Facebook subscribers as possible (11,954,109 users received at least one ad at Thanksgiving and 23,302,290 users received at least one ad at Christmas). The first primary outcome was aggregate holiday travel, measured using mobile phone location data, available at the county level: we find that average distance travelled in high-intensity counties decreased by -0.993 percentage points (95% CI -1.616, -0.371, p-value 0.002) the three days before each holiday. The second primary outcome was COVID-19 infection at the zip-code level: COVID-19 infections recorded in the two-week period starting five days post-holiday declined by 3.5 percent (adjusted 95% CI [-6.2 percent, -0.7 percent], p-value 0.013) in intervention zip codes compared to control zip codes.

Comparison of Knowledge and Information-Seeking Behavior After General COVID-19 Public Health Messages and Messages Tailored for Black and Latinx Communities : A Randomized Controlled Trial.

BACKGROUND: The paucity of public health messages that directly address communities of color might contribute to racial and ethnic disparities in knowledge and behavior related to coronavirus disease 2019 (COVID-19). OBJECTIVE: To determine whether physician-delivered prevention messages affect knowledge and information-seeking behavior of Black and Latinx individuals and whether this differs according to the race/ethnicity of the physician and tailored content. DESIGN: Randomized controlled trial. (Registration: ClinicalTrials.gov, NCT04371419; American Economic Association RCT Registry, AEARCTR-0005789). SETTING: United States, 13 May 2020 to 26 May 2020. PARTICIPANTS: 14 267 self-identified Black or Latinx adults recruited via Lucid survey platform. INTERVENTION: Participants viewed 3 video messages regarding COVID-19 that varied by physician race/ethnicity, acknowledgment of racism/inequality, and community perceptions of mask wearing. MEASUREMENTS: Knowledge gaps (number of errors on 7 facts on COVID-19 symptoms and prevention) and information-seeking behavior (number of web links demanded out of 10 proposed). RESULTS: 7174 Black (61.3%) and 4520 Latinx (38.7%) participants were included in the analysis. The intervention reduced the knowledge gap incidence from 0.085 to 0.065 (incidence rate ratio [IRR], 0.737 [95% CI, 0.600 to 0.874]) but did not significantly change information-seeking incidence. For Black participants, messages from race/ethnicity-concordant physicians increased information-seeking incidence from 0.329 (for discordant physicians) to 0.357 (IRR, 1.085 [CI, 1.026 to 1.145]). LIMITATIONS: Participants' behavior was not directly observed, outcomes were measured immediately postintervention in May 2020, and online recruitment may not be representative. CONCLUSION: Physician-delivered messages increased knowledge of COVID-19 symptoms and prevention methods for Black and Latinx respondents. The desire for additional information increased with race-concordant messages for Black but not Latinx respondents. Other tailoring of the content did not make a significant difference. PRIMARY FUNDING SOURCE: National Science Foundation; Massachusetts General Hospital; and National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

How Much do Existing Borrowers Value Microfinance? Evidence from an Experiment on Bundling Microcredit and Insurance.

Randomized controlled trials have found only modest effects of microfinance, but these studies focus on new clients. Existing estimates may thus understate ongoing gains for more experienced borrowers and the longer-run potential of microfinance. We estimate impacts of microfinance on experienced borrowers, using an episode when a microfinance institution modestly increased existing clients' fees in randomly selected villages (in exchange for a mandatory health insurance policy that turned out to be useless). This increase in fees led to a 22 percentage point decline in loan renewal in treatment villages (95% confidence interval: 16 to 27), compared to control villages where the policy was not introduced. Using this randomly generated variation in microfinance participation among experienced borrowers, we find impacts of microfinance that are strikingly similar to previous estimates for new clients: neither business outcomes nor household consumption were affected, on average. Also, consistent with prior studies, we find significant impacts on business outcomes among clients who had started their businesses before microfinance entered the village (0.06 standard deviation decline in an index of business outcomes from the loss of microfinance, 95% confidence interval: -0.002 to -0.12). However, despite these measured losses, these clients were just as willing to give up microfinance.

Benzocoumarin Hydrazine: A Large Stokes Shift Fluorogenic Sensor for Detecting Carbonyls in Isolated Biomolecules and in Live Cells.

Detection and quantification of biomolecule carbonylation, a critical manifestation of oxidative stress, allows better understanding of associated disease states. Existing approaches for such analyses require further processing of cells and tissues, which leads to loss of both spatial and temporal information about carbonylated biomolecules in cells. Live cell detection of these species requires sensors that are nontoxic, sufficiently reactive with the biocarbonyl in the intracellular milieu, and detectable with commonly available instrumentation. Presented here is a new fluorescent sensor for biomolecule carbonyl detection: a hydrazine derivative of a benzocoumarin, 7-hydrazinyl-4-methyl-2H-benzo[h]chromen-2-one (BzCH), which meets these requirements. This probe is especially well suited for live cell studies. It can be excited by a laser line common to many fluorescence microscopes. The emission maximum of BzCH undergoes a substantial red shift upon hydrazone formation (from ∼430 to ∼550 nm), which is the result of fluorophore disaggregation. Additionally, the hydrazone exhibits an exceptionally large Stokes shift (∼195 nm). The latter properties eliminate self-quenching of the probe and the need to remove unreacted fluorophore for reliable carbonyl detection. Thus, biomolecule carbonylation can be detected and quantified in cells and in cell extracts in a one-step procedure using this probe.

Exposure to sub-inhibitory concentrations of gentamicin, ciprofloxacin and cefotaxime induces multidrug resistance and reactive oxygen species generation in meticillin-sensitive Staphylococcus aureus.

PURPOSE: The role of antibiotics below their MIC in the development of bacterial drug resistance is becoming increasingly important. We investigated the effect of sub-MICs of bactericidal antibiotics on the susceptibility pattern of Staphylococcus aureus and evaluated the role of free radicals. METHODOLOGY: A total of 12 S. aureus strains were recovered from pus samples and their antibiograms determined. The test isolates were treated with sub-MIC levels of tetracycline, gentamicin, ciprofloxacin and cefotaxime. Alterations in their respective breakpoints were observed along with measurements of free radical generation by nitro blue tetrazolium test.Results/Key findings. Gentamicin, ciprofloxacin and cefotaxime exposure significantly altered the breakpoints of exposed isolates against several tested antibiotics and higher levels of free radicals were generated after antibiotic exposure. CONCLUSIONS: Our study demonstrates that sub-MIC levels of antimicrobials can lead to resistance and cross-resistance across several classes of antibiotics in wild strains of S. aureus, possibly by free radical production. The molecular mechanisms behind the acquisition of drug resistance at low antibiotic concentrations and the specific target genes of reactive oxygen speciesneed to be explored further.

The impact of training informal health care providers in India: A randomized controlled trial.

Health care providers without formal medical qualifications provide more than 70% of all primary care in rural India. Training these informal providers may be one way to improve the quality of care where few alternatives exist. We report on a randomized controlled trial assessing a program that provided 72 sessions of training over 9 months to 152 informal providers (out of 304). Using standardized patients ("mystery clients"), we assessed clinical practice for three different conditions to which both providers and trainers were blinded during the intervention, representative of the range of conditions that these providers normally diagnose and treat. Training increased correct case management by 7.9 percentage points (14.2%) but did not affect the use of unnecessary medicines and antibiotics. At a program cost of $175 per trainee, our results suggest that multitopic medical training offers an effective short-run strategy to improve health care.

Development economics. A multifaceted program causes lasting progress for the very poor: evidence from six countries.

We present results from six randomized control trials of an integrated approach to improve livelihoods among the very poor. The approach combines the transfer of a productive asset with consumption support, training, and coaching plus savings encouragement and health education and/or services. Results from the implementation of the same basic program, adapted to a wide variety of geographic and institutional contexts and with multiple implementing partners, show statistically significant cost-effective impacts on consumption (fueled mostly by increases in self-employment income) and psychosocial status of the targeted households. The impact on the poor households lasted at least a year after all implementation ended. It is possible to make sustainable improvements in the economic status of the poor with a relatively short-term intervention.

A rare association of sarcoid-like granuloma with renal cell carcinoma.

Non-necrotizing epithelioid granuloma has been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma, and Hodgkin's lymphoma. They are designated as sarcoid-like reaction, in absence of any evidence of systemic sarcoidosis. But granulomatous reaction in association with renal cell carcinoma (RCC) is uncommon, with only few published reports in the literature. This reaction may have some prognostic importance also. We describe a rare case of conventional (clear cell) RCC associated with epithelioid granulomas within the tumor parenchyma, in a 42-year-old lady without any evidence of systemic sarcoidosis.

Synthesis of isotopically labeled epothilones.

The epothilones, including epothilones B and D, are macrocyclic lactones, which have potent cytotoxicities and promote the polymerization of tubulin to mictotubules by binding to and stabilizing the tubulin polymer. They have a very similar mechanism of action to paclitaxel (Taxol®). The determination of the microtubule-binding conformation of the epothilones is an important piece of information in designing improved analogs for possible clinical use, and internuclear distance information that will assist the determination of this conformation can be obtained by rotational echo double resonance (REDOR) NMR studies of microtubule-bound epothilones with appropriate stable isotope labels. Analogs of epothilone B and epothilone D with [(2) H3 ] and [(19) F] labels were prepared from an advanced precursor for potential use in REDOR NMR studies to determine internuclear distances in tubulin-bound ligand.

The diffusion of microfinance.

To study the impact of the choice of injection points in the diffusion of a new product in a society, we developed a model of word-of-mouth diffusion and then applied it to data on social networks and participation in a newly available microfinance loan program in 43 Indian villages. Our model allows us to distinguish information passing among neighbors from direct influence of neighbors' participation decisions, as well as information passing by participants versus nonparticipants. The model estimates suggest that participants are seven times as likely to pass information compared to informed nonparticipants, but information passed by nonparticipants still accounts for roughly one-third of eventual participation. An informed household is not more likely to participate if its informed friends participate. We then propose two new measures of how effective a given household would be as an injection point. We show that the centrality of the injection points according to these measures constitutes a strong and significant predictor of eventual village-level participation.

Knockdown of aberrantly expressed nuclear localized decorin attenuates tumour angiogenesis related mediators in oral cancer progression model in vitro.

BACKGROUND: Oral cancer accounts for roughly 3% of cancer cases in the world with about 350,000 newly reported cases annually and a 5-year survival rate of only 50%. Majority of oral cancers are squamous cell carcinomas that originate in the oral mucosal epithelial linings. We have previously shown that in human malignant squamous cells carcinoma (SCC-25) as well as in dysplastic oral keratinocytes (DOK), a small leucine-rich multifunctional proteoglycan decorin is aberrantly expressed and localized in the nucleus where it interacts with nuclear epidermal growth factor receptor (EGFR). Post-transcriptional silencing of nuclear decorin significantly reduced IL-8 and IL8-dependent migration and invasion in these dysplastic and malignant oral epithelia. The objective of this study was to further examine the effects of nuclear decorin silencing on angiogenesis and angiogenesis related mediators in this oral cancer progression cell line model. METHODS: We have used multiplex PCR, western blotting, and in vitro endothelial tube formation assay to study angiogenesis and related pathways in nuclear decorin silenced (stable knockdown) DOK and SCC-25 cells. RESULTS: Nuclear decorin knockdown resulted in significant down regulation of IL-8 expression, however IL-10, and TGF-ß expression was not affected in either DOK or SCC25 cells as measured by multiplex RT PCR. IL-8 receptor CXCR 1 and 2 expression was slightly lower in nuclear decorin silenced cells indicating a contributing mechanism in previously shown reduced IL-8 mediated migration and invasion phenotype in these cells. IL-8 is known to induce Matrix metalloproteinase 9 (MMP9) which not only plays a role in tumour migration and invasion but also induces angiogenic switch. We found MMP9 to be significantly reduced in nuclear decorin silenced dysplastic and malignant oral epithelia. Other potent angiogenic mediators, VEGF189 and ANG-1 were either significantly reduced or completely abrogated in these cells. Angiogenesis as measured by endothelial tube-like formations of HUVEC cells was reduced by almost 50 percent when HUVECs were incubated in the presence of conditioned medium form nuclear decorin silenced dysplastic and malignant cell lines as compared to respective controls. CONCLUSIONS: Together these results indicate that aberrantly expressed nuclear localized decorin strongly influences angiogenic potential of dysplastic and malignant oral epithelial cells.