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There is no recognized gold standard method for estimating the number of individuals with substance use disorders (SUDs) seeking help within a given geographical area. This presents a challenge to policy makers in the effective deployment of resources for the treatment of SUDs. Internet search queries related to help seeking for SUDs using Google Trends may represent a low-cost, real-time, and data-driven infoveillance tool to address this shortfall in information. This paper assesses the feasibility of using search query data related to help seeking for SUDs as an indicator of unmet treatment needs, demand for treatment, and predictor of the health harms related to unmet treatment needs. We explore a continuum of hypotheses to account for different outcomes that might be expected to occur depending on the demand for treatment relative to the system capacity and the timing of help seeking in relation to trajectories of substance use and behavior change. We used negative binomial regression models to examine temporal trends in the annual SUD help-seeking internet search queries from Google Trends by US state for cocaine, methamphetamine, opioids, cannabis, and alcohol from 2010 to 2020. To validate the value of these data for surveillance purposes, we then used negative binomial regression models to investigate the relationship between SUD help-seeking searches and state-level outcomes across the continuum of care (including lack of care). We started by looking at associations with self-reported treatment need using data from the National Survey on Drug Use and Health, a national survey of the US general population. Next, we explored associations with treatment admission rates from the Treatment Episode Data Set, a national data system on SUD treatment facilities. Finally, we studied associations with state-level rates of people experiencing and dying from an opioid overdose, using data from the Agency for Healthcare Research and Quality and the CDC WONDER database. Statistically significant differences in help-seeking searches were observed over time between 2010 and 2020 (based on P<.05 for the corresponding Wald tests). We were able to identify outlier states for each drug over time (eg, West Virginia for both opioids and methamphetamine), indicating significantly higher help-seeking behaviors compared to national trends. Results from our validation analyses across different outcomes showed positive, statistically significant associations for the models relating to treatment need for alcohol use, treatment admissions for opioid and methamphetamine use, emergency department visits related to opioid use, and opioid overdose mortality data (based on regression coefficients having P≤.05). This study demonstrates the clear potential for using internet search queries from Google Trends as an infoveillance tool to predict the demand for substance use treatment spatially and temporally, especially for opioid use disorders.

Among vaccines administered to children are those targeting rotavirus, a segmented double-stranded RNA virus that represents a major cause of severe gastroenteritis. To explore the feasibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that contained coding cassettes for NSP3, a translational 2A stop-restart signal, and a FLAG-tagged portion of the SARS-CoV-2 spike (S) protein: S1 fragment, N-terminal domain (NTD), receptor-binding domain (RBD), extended RBD (ExRBD), or S2 core (CR) domain. Generation of rSA11 containing the S1 coding sequence required a sequence insertion of 2.2 kbp, the largest such insertion yet introduced into the rotavirus genome. Immunoblotting showed that rSA11 viruses containing the smaller NTD, RBD, ExRBD, and CR coding sequences expressed S-protein products of expected size, with ExRBD expressed at highest levels. These rSA11 viruses were genetically stable during serial passage. In contrast, the rSA11 virus containing the full-length S coding sequence (rSA11/NSP3-fS1) failed to express its expected 80 kDa fS1 product, for unexplained reasons. Moreover, rSA11/NSP3-fS1 was genetically unstable, with variants lacking the S1 insertion appearing during serial passage. Nonetheless, these results emphasize the potential usefulness of rotavirus vaccines as expression vectors of immunogenic portions of the SARS-CoV-2 S protein, including NTD, RBD, ExRBD, and CR, that have sizes smaller than the S1 fragment.

Despite the growing research done on sacred spaces in Buddhist Myanmar, no attention has yet been given to the role dreams play in the selection and development of such spaces. This article will address this lacuna by exploring how dreams are regarded by 20th–21st centuries Buddhists in Myanmar, as evidenced in autobiographies, ethnographic work, and popular literature in relation to the creation and evolution of sacred places. Although there are many kinds of sacred sites in Myanmar, this article will look specifically at Buddhist stupas, commonly referred to in Burmese as, pagoda or zedi. These pagodas, found in nearly every part of Buddhist Myanmar, are also those structures most prevalent in Buddhist dream accounts and often take on phantasmagorical qualities when those same Buddhists attempt to recreate the pagodas of their dreams.

Patients with atopic dermatitis (AD) who do not adequately respond to topical therapy and phototherapy often need systemic immunomodulatory treatment to control their symptoms. Conventional systemic agents, such as ciclosporin, azathioprine, and methotrexate, have been used for decades, but there are concerns about their safety profile. There are now many novel systemic agents emerging through clinical trials, which may have great potential in the treatment of AD. Despite this, there are very few data comparing the performance of these drugs against each other. The purpose of this article is to review the current systemic therapies in AD and present an indirect comparison of systemic AD treatments using effectiveness and safety data from published randomised controlled trials, highlighting important remaining gaps in knowledge. Although the latest developments in systemic AD treatments are exciting and dearly needed, further work is required before the promise of a therapeutic revolution becomes reality.

BackgroundImmune checkpoint inhibitors (ICI) have revolutionized the management of lung tumors decreasing mortality rates. However, the response rates to these ICI drugs are limited, and identifying those patients who are most likely to benefit remains a clinical challenge. Due to the complex nature of the host immune response, tissue-based biomarker development for immunotherapy (IO) is challenging. Consequently, there is a critical unmet need to develop accurate, validated imaging biomarkers to predict which Non-Small Cell Lung Cancer (NSCLC) patients will benefit from IO. Airway deformations such as central airway obstruction can be considered an important manifestation of cancer aggressiveness or metastatic disease and may have a significant impact on therapeutic refractoriness. In this study, we sought to evaluate whether quantitative measurements of lung airway morphology (QuaLM) on baseline CT scans are associated with response and overall survival in NSCLC patients treated with ICI.MethodsIn this retrospective study, 80 cases who underwent 2–3 cycles of PD1/PD-L1 ICI therapy (nivolumab/pembrolizumab/atezolizumab) were included. RECIST v1.1 was used to define ‘responders’ and ‘non-responders’. Patients were randomly divided into a training (n=40) and a test set (n=40). A region growing algorithm is applied to the trachea, identified by Hough transform, to segment bronchi and bronchioles (figure 1a). 14 QuaLM features were extracted from segmented airway on CT scans. Wilcoxson ranksum test is used to identify the predictive QuaLM features. The top 4 QuaLM features in conjunction with a linear discriminant machine learning classifier were used to predict the response to IO. We also built a QuaLM risk score using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict overall survival (OS).ResultsThe response prediction model trained with top QuaLM features (table 1) predicts responders to ICI with an area under research operating characteristic curve (ROC AUC) of 0.67±0.08 (figure 1.b) in the training (St) and AUC=0.63 in the test set (Sv). The airway radiomics risk-score was found to be significantly associated with OS in St (HR=2.34, 95% CI:[1.08–5.07], P=0.008) and Sv (HR=2.55, 95% CI:[0.8–8.1], P=0.034) (figure 1.c).ConclusionsQuaLM features were able to distinguish responders from non-responders and also were found to be associated with OS for NSCLC patients treated with ICI. With additional validation, QuaLM could potentially serve as an imaging biomarker of ICI response assessment for NSCLC patients. This could allow the selection of NSCLC patients who will benefit from IO and help design more rational clinical trials with a combination of IO.Abstract 37 Figure 1a) The pipeline of airway segmentation includes trachea identification, segmenting the lung regions from surrounding anatomy, and segmenting the airway by applying a region-growing algorithm. b) ROC curve of QuaLM model for predicting IO response from baseline CT scans. c) Kaplan Meier curve analysis reveals dichotomization of patients into low risk and high-risk groups with distinct survival patterns based off QuaLM features. d,e) An example airway structure of a non-responder and a responder to ICI.Abstract 37 Table 1Predictive airway features that found to be significantly different among responders and non-responders to IO

Since the early twentieth century, groups of Burmese Buddhist sorcerers and their followers have taken on the duty of guarding the Buddha's sāsana from colonial, ideological, and Islamic threats. Sāsana (broadly, the teachings of the Buddha and the institutions and practices that support them) and how it should be sustained in the face of its inevitable demise have been central concerns of these societies, expressed in both their textual and oral representations. To illustrate this tension between endurance and change, this article explores ideas of the life cycle of the sāsana and how ideas about its responsibility to wider communities of Burmese Buddhists became expressed through the intersection of sāsana and sorcery. Examining the ways these associations understood themselves to be protecting and propagating the sāsana through various means demonstrates how sāsana vitality gave their beliefs and actions a distinct collective and collectively ethical tone.

Over the years of studying the magical powers of words in the Burmese Buddhist context, I spent much of my research on the inner workings of the letter and phrase combinations and how the correct construction, combination and usage of these words, known in Burmese as inn, aing, and sama made for a potent prophylactic against a host of maladies. So focused had I been on the words that I had not taken the time to consider the individual letters, in and of themselves, before they went on to be combined into esoteric phrases and diagrams. Moreover, I had devoted my research to examining the ways Burmese words were predominantly seen to protect, purify, and even attack, but had never considered other ways in which letters may ‘do’ things, as Fox points out: namely, ‘represent cultural identity’; ‘embody and transmit knowledge’; ‘animate and enable’; ‘render things usable and so nameable’; ‘turn on their user’; and ‘both incur and pay debts’. While I cannot address each of these points in this short essay, I would like to discuss how Fox's book helped me to discover new ways of interpreting how letters and words may transfer their powers to people and things (‘embody and transmit knowledge’), as well as encouraging me to look into concepts of how, and if, letters can be considered ‘alive’ (‘animate and enable’) in the Burmese context.

This article on visions, possessions, and healing examines the Burmese cultural atmosphere in which stories, devotional literature, and religious magazines all recognize, endorse, and publicize the ways Buddhist weizzā (wizard-saints) interact with their female devotees to heal specific illnesses. Devotees possessed by a weizzā and carrying out his bidding can be seen as a creative yet culturally sanctioned response to restrictive gender roles, a means for expressing otherwise illicit thoughts or feelings, and an economic strategy for women who have few options beyond traditional wifely or daughter roles. They are able to renegotiate the often silent and passive roles assigned to them by the religious and medical cultures by setting the experience of sickness into a new narrative framework in which the weizzā are the source of all healing. Through the power of their wishes and within the flexible parameters of devotional practice, these women enact significant and positive changes in their lives and those around them.

We carried out a scoping review to characterize the primary quantitative evidence addressing changes in key individual/structural determinants of substance use risks and health outcomes over the first two waves of the COVID-19 pandemic in the United States (US). We systematically queried the LitCovid database for US-only studies without date restrictions (up to 6 August 2021). We extracted quantitative data from articles addressing changes in: (a) illicit substance use frequency/contexts/behaviors, (b) illicit drug market dynamics, (c) access to treatment and harm reduction services, and (d) illicit substance use-related health outcomes/harms. The majority of 37 selected articles were conducted within metropolitan locations and leveraged historical timeseries medical records data. Limited available evidence supported changes in frequency/behaviors/contexts of substance use. Few studies point to increases in fentanyl and reductions in heroin availability. Policy-driven interventions to lower drug use treatment thresholds conferred increased access within localized settings but did not seem to significantly prevent broader disruptions nationwide. Substance use-related emergency medical services’ presentations and fatal overdose data showed a worsening situation. Improved study designs/data sources, backed by enhanced routine monitoring of illicit substance use trends, are needed to characterize substance use-related risks and inform effective responses during public health emergencies.