Search

Background: High dose rate brachytherapy is commonly used in the treatment of prostate cancer. Treatment planning is often performed under transrectal ultrasound (US) guidance, but brachytherapy needles can be challenging to digitize due to the presence of poor US conspicuity and imaging artifacts. The plan accuracy and quality, however, are dependent on the proper visualization of the needles with millimeter accuracy. Purpose: This work describes a technique for generating a color overlay of needle locations atop the grayscale US image. Prototype devices were developed to produce vibrations in the brachytherapy needles that generate a high contrast color Doppler (CD) signal that highlights the needle locations with superior contrast and reduced artifacts. Denoted by the acronym color VISION (Vibrationally Induced Shimmering for Identifying an Object's Nature), the technology has the potential to improve applicator conspicuity and facilitate automated applicator digitization. Methods: Three prototype vibrational devices with frequencies between 200–450 Hz were designed in‐house and evaluated with needle implants in a phantom and cadaveric male pelvis using: (1) an actuator attached to the front of a prostate needle template; (2) an actuator attached to the top of the needle template; and (3) a hand‐held actuator with a stylet, inserted directly into a needle's inner lumen. Acquired images were postprocessed in MATLAB to evaluate the potential for automated digitization. Results: All prototype devices produced localized shimmering in implanted brachytherapy needles in both the axial and sagittal planes. The template mounted actuators provided better vibrational coupling and ease of operation than the stylet prototype. The Michelson contrast, or visibility, of the shimmering CD signal was 100% compared with ≤40% for B‐mode imaging of a single needle. Proof‐of‐principle for automated applicator digitization using only the CD signal was demonstrated. Conclusions: The color VISION prototype devices successfully coupled mechanical vibrations into brachytherapy needles to generate US CD shimmering and accurately highlight brachytherapy needle locations. The high contrast and natively registered signal are promising for future work to automate the needle digitization and provide a real‐time visual overlay of the applicator on the B‐mode US image. [ABSTRACT FROM AUTHOR]

Summary: Background: Data on oral vancomycin for primary sclerosing cholangitis (PSC)‐associated inflammatory bowel disease (IBD) are limited. Aims: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. Methods: In this retrospective multi‐centre cohort study, we matched vancomycin‐treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. Results: 113 PSC‐IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin‐treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97–6.31; adjusted OR [aOR] 5.24, 95% CI 2.68–10.22). Benefit was maintained in sensitivity analyses restricted to non‐transplanted patients and those with baseline moderate–severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002–7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). Conclusion: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has led to unprecedented life disruptions among young adults, including increased job insecurity and financial strain. Mental health problems and substance use have also increased during the pandemic, with young adults particularly vulnerable to experiencing these challenges. This study examines trajectories of financial distress among young adults during the pandemic and their associations with depression, anxiety, and hazardous alcohol and cannabis use. Data from 473 young adults (ages 22–29) recruited in the Northwest United States were collected from April/May 2020 to July/August 2021. Financial distress trajectories were identified using growth mixture modeling. Negative binomial models were used to examine associations between financial distress trajectories and distal outcomes of depression, anxiety, alcohol, and cannabis use. Three distinct trajectories were identified, revealing Low, Moderate, and High financial distress experiences. Individuals with "Moderate" and "High" trajectories showed significantly greater depressive and anxiety symptom scores compared with those in the "Low" financial distress trajectory group. Trajectories were not associated with subsequent levels of alcohol or cannabis use. Young adult mental health remains a priority during periods of economic downturn. Providers must be aware of the psychological challenges imposed by financial distress among young adults to address worsening mental health symptoms. [ABSTRACT FROM AUTHOR]

Background: An important life‐course event with respect to alcohol and cannabis use is turning 21 years of age, which may be associated with increases in use of these substances due to celebrations during the month and easier access to them on and following this birthday. We examined the trajectories of alcohol and cannabis use behaviors in the months leading up to, during, and following the 21st birthday month. We also examined whether the use trajectories vary by college status and baseline levels of use. Methods: We used data from 203 young adults recruited from the Greater Seattle region who turned 21 during the course of the study. Surveys were administered each month for 24 consecutive months. Measures included the typical number of drinks per week for the past month, the frequency of heavy episodic drinking, the number of cannabis use days, and any simultaneous alcohol and cannabis use. Multilevel spline models were run that estimated linear slopes over time at four intervals: (1) up to 1 month before the 21st birthday month; (2) from 1 month before to the month of the 21st birthday; (3) from the 21st birthday month to 1 month following; and (4) from 1 month following the 21st birthday month through all following months. Results: Alcohol use, generally, and simultaneous alcohol and cannabis use showed sharp increases from the month before the 21st birthday month to the 21st birthday month and decreases following the 21st birthday month. For cannabis use, there were significant increases in the months leading up to the 21st birthday and no other significant changes during other time intervals. Patterns differed by baseline substance use and college status. Conclusions: Findings from the current study have implications for the timing and personalization of prevention and intervention efforts. Event‐specific 21st birthday interventions may benefit from incorporating content targeting specific hazardous drinking behaviors in the month prior to the 21st birthday. [ABSTRACT FROM AUTHOR]

Drug development teams must evaluate the risk/benefit profile of new drug candidates that perpetrate drug–drug interactions (DDIs). Real‐world data (RWD) can inform this decision. The purpose of this study was to develop a predicted impact score for DDIs perpetrated by three hypothetical drug candidates via CYP3A, CYP2D6, or CYP2C9 in type 2 diabetes mellitus (T2DM), obesity, or migraine. Optum Market Clarity was analyzed to estimate use of CYP3A, CYP2D6, or CYP2C9 substrates classified in the University of Washington Drug Interaction Database as moderate sensitive, sensitive, narrow therapeutic index, or QT prolongation. Scoring was based on prevalence of exposure to victim substrates and characteristics (age, polypharmacy, duration of exposure, and number of prescribers) of those exposed. The study population of 14,163,271 adults included 1,579,054 with T2DM, 3,117,753 with obesity, and 410,436 with migraine. For T2DM, 71.3% used CYP3A substrates, 44.3% used CYP2D6 substrates, and 44.3% used CYP2C9 substrates. For obesity, 57.1% used CYP3A substrates, 34.6% used CYP2D6 substrates, and 31.0% used CYP2C9 substrates. For migraine, 64.1% used CYP3A substrates, 44.0% used CYP2D6 substrates, and 28.9% used CYP2C9 substrates. In our analyses, the predicted DDI impact scores were highest for DDIs involving CYP3A, followed by CYP2D6, and CYP2C9 substrates, and highest for T2DM, followed by migraine, and obesity. Insights from RWD can be used to estimate a predicted DDI impact score for pharmacokinetic DDIs perpetrated by new drug candidates currently in development. This score can inform the risk/benefit profile of new drug candidates in a target patient population. [ABSTRACT FROM AUTHOR]

Cyanobacterial harmful algal blooms (cyanoHABs) can harm people, animals, and affect consumptive and recreational use of inland waters. Monitoring cyanoHABs is often limited. However, chlorophyll‐a (chl‐a) is a common water quality metric and has been shown to have a relationship with cyanobacteria. The World Health Organization (WHO) recently updated their previous 1999 cyanoHAB guidance values (GVs) to be more practical by basing the GVs on chl‐a concentration rather than cyanobacterial counts. This creates an opportunity for widespread cyanoHAB monitoring based on chl‐a proxies, with satellite remote sensing (SRS) being a potentially powerful tool. We used Sentinel‐2 (S2) and Sentinel‐3 (S3) to map chl‐a and cyanobacteria, respectively, classified chl‐a values according to WHO GVs, and then compared them to cyanotoxin advisories issued by the California Department of Water Resources (DWR) at San Luis Reservoir, key infrastructure in California's water system. We found reasonably high rates of total agreement between advisories by DWR and SRS, however rates of agreement varied for S2 based on algorithm. Total agreement was 83% for S3, and 52%–79% for S2. False positive and false negative rates for S3 were 12% and 23%, respectively. S2 had 12%–80% false positive rate and 0%–38% false negative rate, depending on algorithm. Using SRS‐based chl‐a GVs as an early indicator for possible exposure advisories and as a trigger for in situ sampling may be effective to improve public health warnings. Implementing SRS for cyanoHAB monitoring could fill temporal data gaps and provide greater spatial information not available from in situ measurements alone. Plain Language Summary: Lakes often have algal blooms that create a water quality concern, especially when they contain cyanobacteria, which can be toxic to both humans and animals. These harmful algal blooms are of great concern in areas with limited water supply in states such as California. While it is often difficult and costly to collect and monitor toxin concentrations, monitoring concentrations of chlorophyll‐a (chl‐a) –a measure of how much algae are present—is relatively common and can even be accomplished using satellite remote sensing. There have been multiple studies that have found a relationship between toxins produced by cyanobacteria and chl‐a. The World Health Organization (WHO) has recently released (2021) an updated release of their previous 1999 guidance values for toxin monitoring based on chl‐a concentration. With satellite data, we were able to measure chl‐a concentration in a major reservoir in California, and then classify the chl‐a measurements into the WHO's guidance values for toxins. We compared the satellite‐based guidance values to the public advisory levels currently set by the California Department of Water Resources. Our results indicate that SRS of chl‐a is a reasonable substitute for cyanobacteria toxin advisories, and our framework can be applied to similar cyanobacteria dominated lakes. Key Points: The World Health Organization (WHO) updated cyanobacteria harmful algal blooms (cyanoHABs) guidelines for chlorophyll‐a (chl‐a) as a proxyWith satellite remote sensing (SRS), we estimated and classified chl‐a to compare cyanotoxins advisories used by CaliforniaThis study provides a framework for evaluating public health utility of SRS for enhancing cyanotoxin monitoring globally [ABSTRACT FROM AUTHOR]

Introduction: Exposure to media with alcohol‐related content is a known risk for alcohol use and related harms among young people. The present study used longitudinal self‐report data on exposure to media with alcohol‐related content to examine age trajectories across young adulthood and to estimate associations with heavy episodic drinking (HED) and negative consequences. Method: Participants were 201 high‐risk young adults enrolled in 2‐ and 4‐year colleges (ages 18–25 at screening; 63.7% female). Repeated assessments occurred at four timepoints across a 12‐month period. Results: Self‐reported exposure to both positively and negatively portrayed alcohol‐related media content decreased with age. Between‐persons, controlling for alcohol use frequency, exposure to positive alcohol‐related media content was positively associated with HED, and exposure to negative alcohol‐related media content was inversely associated with HED; no within‐person effects on HED were significant. For negative consequences, controlling for alcohol quantity, exposure to positive media content was associated with more negative consequences both between‐ and within‐persons. Unexpectedly, exposure to negatively portrayed media content was positively associated with negative consequences at the within‐person level. Discussion and Conclusions: Trajectories in exposure to media with alcohol‐related content showed that relatively younger participants reported greater exposure, highlighting the need for policy and prevention efforts to protect this vulnerable demographic. Findings generally indicated that positive portrayals of alcohol use increase alcohol‐related risks. Moreover, increased exposure to negative portrayals in a given assessment was associated with more negative consequences—potentially by normalising or glorifying high‐risk drinking and consequences, though mechanistic/causal research is needed. [ABSTRACT FROM AUTHOR]

A 3D‐printed array of hollow microneedles (HMNs) is designed and fabricated using a high‐resolution stereolithography 3D printer and assembled with a 3D‐printed reservoir that incorporates a Luer lock mechanism, ensuring standard and secure connection to syringes. The proof‐of‐concept needle designs consist of half‐eccentric and concentric conical tip shapes, each arrayed with two different interspacing values. After the geometrical features of the devices are characterized, the devices are tested ex vivo in porcine skin to evaluate the impact of tip shape and interspacing on the depth of penetration and the efficacy of the devices in delivering fluids (such as tattoo ink) into the dermis. Overall, the 3D‐printed HMNs can deliver fluids into the target layer of skin. Refinement of the design is ongoing with the ultimate aim to provide alternatives for intradermal drug delivery and diagnostic imaging, such as superficial lymphography. [ABSTRACT FROM AUTHOR]

Objective Background Method Results Conclusions Test whether global self‐reports of urgency moderated the within‐person associations of affect and impulsive behaviors.Negative urgency is a personality trait that is a risk factor for a range of psychopathology. Although it is assumed that global self‐reports of urgency measure individual tendencies to act more impulsively in the face of negative emotions, evidence from ecological momentary assessment studies is mixed.In this Registered Report, we used ecological momentary assessment data from a large sample of young adults (n = 496, age 18–22, 5 surveys per day for 40 days).All forms of momentary impulsivity were impaired in moments when people reported more intense negative emotions, but global self‐reports of urgency did not explain individual differences in this association. Moreover, averaged affective states, rather than specific dimensions, affective circumplex, or appraisals, best predicted impulsive states.Results suggest that face‐valid interpretations of global self‐report of urgency are inaccurate, and it may be important to understand how some people come to understand themselves as high on urgency rather than assuming that people's self‐reports of their motivations are accurate. Momentary experiences of emotions globally impact multiple weakly to moderately associated impulsive behaviors, and future research should seek to understand both when and for whom these associations are strongest. [ABSTRACT FROM AUTHOR]

Young adulthood is a developmental period during which individuals experience shifts in their social roles in various domains, which coincides with a period of time that is also high risk for lifetime peaks in alcohol use. The current study examined age‐related changes in heavy episodic drinking (HED) and high‐intensity drinking (HID) and associations with short‐term (i.e., monthly) variation in young adults' social roles over a 2.5‐year period in a community sample of young adults who reported past‐year alcohol use (N = 778, baseline age range 18–23). Results showed probabilities of past‐month HED and HID changed in a nonlinear fashion across ages 18–26 with greater probabilities of use at younger ages. Most participants did not report being in the same social role status every sampled month, underscoring the presence of short‐term role variation. Living with parents and being in a serious romantic relationship in a given month were negatively associated with past‐month HED. Living with parents in a given month was also negatively associated with past‐month HID. Being a 4‐year college student and being employed full‐time in a given month were not significantly related to either outcome. Findings provided partial evidence that monthly statuses were associated with heavy drinking. Several avenues for future research are described in light of the findings. [ABSTRACT FROM AUTHOR]