Association of Intrinsic Functional Connectivity between the Locus Coeruleus and Salience Network with Attentional Ability.

The locus coeruleus (LC) is a brainstem region associated with broad neural arousal because of norepinephrine production, but it has increasingly been associated with specific cognitive processes. These include sustained attention, with deficits associated with various neuropsychological disorders. Neural models of attention deficits have focused on interrupted dynamics between the salience network (SAL) with the frontoparietal network, which has been associated with task-switching and processing of external stimuli, respectively. Conflicting findings for these regions suggest the possibility of upstream signaling leading to attention dysfunction, and recent research suggests LC involvement. In this study, resting-state functional connectivity and behavioral performance on an attention task was examined within 584 individuals. Analysis revealed significant clusters connected to LC activity in the SAL. Given previous findings that attention deficits may be caused by SAL network switching dysfunctions, findings here further suggest that dysfunction in LC-SAL connectivity may impair attention.

Reversing Inequity in Mpox Vaccine Distribution, Fulton County, Georgia, June-September 2022.

Racial/ethnic disparities in the administration of mpox vaccine in Fulton County, Georgia, threatened to undermine the effectiveness of the response. To counteract this inequity, the Fulton County Board of Health partnered with local agencies serving Black and Latino men who have sex with men to coordinate efforts and reserve blocks of time for clients of these agencies to receive a vaccine. The disparities were reversed and approached equity with case rates. (Am J Public Health. 2023;113(12):1263-1266. https://doi.org/10.2105/AJPH.2023.307416).

Sex Hormone Therapy and Tenofovir Diphosphate Concentration in Dried Blood Spots: Primary Results of the Interactions Between Antiretrovirals And Transgender Hormones Study.

BACKGROUND: Sex hormone and preexposure prophylaxis (PrEP) drug interactions among transgender women (TGW), transgender men (TGM), and cisgender men (CGM) are not fully understood. METHODS: TGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral coformulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2- and 4-week samples from Directly Observed Therapy Dried Blood Spots (DOT-DBS) Study (NCT02022657). RESULTS: From May 2017 to June 2018, 24 TGM and 24 TGW were enrolled. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW, respectively. Historical controls included 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference, -6%; 95% confidence interval [CI], -21% to 12%; P = .47), comparable between TGW and CGM (mean difference, -12%; 95% CI, -27% to 7%; P = .21) and were lower among TGM compared with CGW (mean difference, -23%; 95% CI, -36% to -7%; P = .007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from human immunodeficiency virus. CONCLUSIONS: CGM, TGM, and TGW had comparable TFV-DP concentrations in dried blood spots after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use. CLINICAL TRIALS REGISTRATION: NCT04050371.

QCM-D Investigation of Swelling Behavior of Layer-by-Layer Thin Films upon Exposure to Monovalent Ions.

Polyelectrolyte multilayers and layer-by-layer assemblies are susceptible to structural changes in response to ionic environment. By altering the salt type and ionic strength, structural changes can be induced by disruption of intrinsically bound ion pairs within the multilayer network via electrostatic screening. Notably, high salt concentrations have been used for the purposes of salt-annealing and self-healing of LbL assemblies with KBr, in particular, yielding a remarkably rapid response. However, to date, the structural and swelling effects of various monovalent ion species on the behavior of LbL assemblies remain unclear, including a quantitative view of ion content in the LbL assembly and thickness changes over a wide concentration window. Here, we investigate the effects of various concentrations of KBr (0 to 1.6 M) on the swelling and de-swelling of LbL assemblies formed from poly(diallyldimethylammonium) polycation (PDADMA) and poly(styrene sulfonate) polyanion (PSS) in 0.5 M NaCl using quartz-crystal microbalance with dissipation (QCM-D) monitoring as compared to KCl, NaBr, and NaCl. The ion content after salt exchange is quantified using neutron activation analysis (NAA). Our results demonstrate that Br- ions have a much greater effect on the structure of as-prepared thin films than Cl- at ionic strengths above assembly conditions, which is possibly caused by the more chaotropic nature of Br-. It is also found that the anion in general dominates the swelling response as compared to the cation because of the excess PDADMA in the multilayer. Four response regimes are identified that delineate swelling due to electrostatic repulsion, slight contraction, swelling due to doping, and film destruction as ionic strength increases. This understanding is critical if such materials are to be used in applications requiring submersion in chemically dynamic environments such as sensors, coatings on biomedical implants, and filtration membranes.

Comparison of KBr and NaCl effects on the glass transition temperature of hydrated layer-by-layer assemblies.

The influence of assembly and post-assembly conditions on the glass transition temperature of free-standing poly(diallyldimethyl ammonium) (PDADMA)/poly(4-styrene sulfonate) (PSS) layer-by-layer (LbL) films assembled in 0.5M NaCl and 0.5M KBr are explored using modulated differential scanning calorimetry. Upon completion, PDADMA/PSS LbL assemblies are hydrated using solutions containing various concentrations of KBr. The data indicate that water provides the primary driving force for changes in the glass transition temperature of completed films rather than the post-assembly salt type. However, upon changing the assembly salt conditions from NaCl to KBr, the glass transition temperature shows a decrease of nearly 20 °C. Additionally, the composition of the films upon analysis with 1H NMR spectroscopy and neutron activation analysis indicates an elevated number of extrinsic binding sites within the film structure when KBr is the assembly salt. This shows a clear link between the assembly conditions and the internal structure and, therefore, the thermal properties of PDADMA/PSS LbL assemblies.

Revitalizing condom-centered HIV prevention strategies.

HIV infection rates remain steady in the USA despite the numerous prevention programs and tools available. Condoms play a central role in HIV prevention because they are highly effective, readily available, and affordable. Unfortunately, condom promotion efforts often incite fear as a motive force, while also taking the common "one-size-fits-all" approach. Reframing condom promotion through a sexual health framework, focusing on pleasure and highlighting condom fit issues, improves intervention efficacy. Condom distribution policies may further perpetuate condom users' difficulty, by withholding particular condom styles, brands, and information highlighting the nuances in shape, size, and material. Condom education and distribution practices focused on pleasure, proper fit, and condom access issues might increase condom utilization among high-risk populations.

High-intensity compared to moderate-intensity training for exercise initiation, enjoyment, adherence, and intentions: an intervention study.

BACKGROUND: Understanding exercise participation for overweight and obese adults is critical for preventing comorbid conditions. Group-based high-intensity functional training (HIFT) provides time-efficient aerobic and resistance exercise at self-selected intensity levels which can increase adherence; behavioral responses to HIFT are unknown. This study examined effects of HIFT as compared to moderate-intensity aerobic and resistance training (ART) on exercise initiation, enjoyment, adherence, and intentions. METHODS: A stratified, randomized two-group pre-test posttest intervention was conducted for eight weeks in 2012 with analysis in 2013. Participants (n = 23) were stratified by median age (< or ≥ 28) and body mass index (BMI; < or ≥ 30.5). Participants were physically inactive with an average BMI of 31.1 ± 3.5 kg/m2, body fat percentage of 42.0 ± 7.4%, weight of 89.5 ± 14.2 kg, and ages 26.8 ± 5.9 years. Most participants were white, college educated, female, and married/engaged. Both groups completed 3 training sessions per week. The ART group completed 50 minutes of moderate aerobic exercise each session and full-body resistance training on two sessions per week. The HIFT group completed 60-minute sessions of CrossFit™ with actual workouts ranging from 5-30 minutes. Participants completed baseline and posttest questionnaires indicating reasons for exercise initiation (baseline), exercise enjoyment, and exercise intentions (posttest). Adherence was defined as completing 90% of exercise sessions. Daily workout times were recorded. RESULTS: Participants provided mostly intrinsic reasons for exercise initiation. Eighteen participants adhered (ART = 9, 81.8%; HIFT = 9, 75%). HIFT dropouts (p = .012) and ART participants (p = .009) reported lower baseline exercise enjoyment than HIFT participants, although ART participants improved enjoyment at posttest (p = .005). More HIFT participants planned to continue the same exercise than ART participants (p = .002). No significant changes in BMI or body composition were found. Workouts were shorter for HIFT than ART (p < .001). CONCLUSIONS: HIFT participants spent significantly less time exercising per week, yet were able to maintain exercise enjoyment and were more likely to intend to continue. High-intensity exercise options should be included in public health interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: http://NCT02185872. Registered 9 July 2014.

A collection of 157 individual neuromelanin-sensitive images accompanied by non-linear neuromelanin-sensitive atlas and a probabilistic locus coeruleus atlas.

The current dataset aims to support and enhance the research reliability of neuromelanin regions in the brainstem, such as locus coeruleus (LC), by offering raw neuromelanin-sensitive images. The dataset includes raw neuromelanin-sensitive images from 157 healthy individuals (8-64 years old). In addition, leveraging individual neuromelanin-sensitive images, a non-linear neuromelanin-sensitive atlas, generated through an iterative warping process, is included to tackle the common challenge of a limited field of view in neuromelanin-sensitive images. Finally, the dataset encompasses a probabilistic LC atlas generated through a majority voting approach with pre-existing multiple atlas-based segmentations. This process entails warping pre-existing atlases onto individual spaces and identifying voxels with a majority consensus of over 50 % across the atlases. This LC probabilistic atlas can minimize uncertainty variance associated with choosing a specific single atlas.

Hybrid healthcare unit recommendation system using computational techniques with lung cancer segmentation.

Introduction: Our research addresses the critical need for accurate segmentation in medical healthcare applications, particularly in lung nodule detection using Computed Tomography (CT). Our investigation focuses on determining the particle composition of lung nodules, a vital aspect of diagnosis and treatment planning. Methods: Our model was trained and evaluated using several deep learning classifiers on the LUNA-16 dataset, achieving superior performance in terms of the Probabilistic Rand Index (PRI), Variation of Information (VOI), Region of Interest (ROI), Dice Coecient, and Global Consistency Error (GCE). Results: The evaluation demonstrated a high accuracy of 91.76% for parameter estimation, confirming the effectiveness of the proposed approach. Discussion: Our investigation focuses on determining the particle composition of lung nodules, a vital aspect of diagnosis and treatment planning. We proposed a novel segmentation model to identify lung disease from CT scans to achieve this. We proposed a learning architecture that combines U-Net with a Two-parameter logistic distribution for accurate image segmentation; this hybrid model is called U-Net++, leveraging Contrast Limited Adaptive Histogram Equalization (CLAHE) on a 5,000 set of CT scan images.

Excessive Functional Coupling With Less Variability Between Salience and Default Mode Networks in Autism Spectrum Disorder.

BACKGROUND: Atypical activity in the salience network (SN) and default mode network (DMN) has been previously reported in individuals with autism spectrum disorder (ASD). However, no study to date has investigated the nature and dynamics of the interaction between these two networks in ASD. METHODS: Here, we aimed to characterize the functional connectivity between the SN and the DMN by using resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange and comparing individuals with ASD (n = 325) to a typically developing group (n = 356). We examined static and dynamic levels of functional connectivity using the medial prefrontal cortex (mPFC) seed as a core region of the DMN. RESULTS: We found that individuals with ASD have higher mPFC connectivity with the insula, a core region of the SN, when compared with the typical development group. Moreover, the mPFC-insula coupling showed less variability in ASD compared with the typical development group. A novel semblance-based network dynamic analysis further confirmed that the strong mPFC-insula coupling in the ASD group reduced spontaneous attentional shift for possible external elements of the environment. Indeed, we found that excessive mPFC-insula coupling was significantly associated with a tendency for reduced social responsiveness. CONCLUSIONS: These findings suggest that the internally oriented cognition in individuals with ASD may be due to excessive coupling between the DMN and the SN.

Age-Related Intrinsic Functional Connectivity Changes of Locus Coeruleus from Childhood to Older Adults.

The locus coeruleus is critical for selective information processing by modulating the brain's connectivity configuration. Increasingly, studies have suggested that LC controls sensory inputs at the sensory gating stage. Furthermore, accumulating evidence has shown that young children and older adults are more prone to distraction and filter out irrelevant information less efficiently, possibly due to the unoptimized LC connectivity. However, the LC connectivity pattern across the life span is not fully examined yet, hampering our ability to understand the relationship between LC development and the distractibility. In this study, we examined the intrinsic network connectivity of the LC using a public fMRI dataset with wide-range age samples. Based on LC-seed functional connectivity maps, we examined the age-related variation in the LC connectivity with a quadratic model. The analyses revealed two connectivity patterns explicitly. The sensory-related brain regions showed a positive quadratic age effect (u-shape), and the frontal regions for the cognitive control showed a negative quadratic age effect (inverted u-shape). Our results imply that such age-related distractibility is possibly due to the impaired sensory gating by the LC and the insufficient top-down controls by the frontal regions. We discuss the underlying neural mechanisms and limitations of our study.

3D CNN with Visual Insights for Early Detection of Lung Cancer Using Gradient-Weighted Class Activation.

The 3D convolutional neural network is able to make use of the full nonlinear 3D context information of lung nodule detection from the DICOM (Digital Imaging and Communications in Medicine) images, and the Gradient Class Activation has shown to be useful for tailoring classification tasks and localization interpretation for fine-grained features and visual explanation for the internal working. Gradient-weighted class activation plays a crucial role for clinicians and radiologists in terms of trusting and adopting the model. Practitioners not only rely on a model that can provide high precision but also really want to gain the respect of radiologists. So, in this paper, we explored the lung nodule classification using the improvised 3D AlexNet with lightweight architecture. Our network employed the full nature of the multiview network strategy. We have conducted the binary classification (benign and malignant) on computed tomography (CT) images from the LUNA 16 database conglomerate and database image resource initiative. The results obtained are through the 10-fold cross-validation. Experimental results have shown that the proposed lightweight architecture achieved a superior classification accuracy of 97.17% on LUNA 16 dataset when compared with existing classification algorithms and low-dose CT scan images as well.

Molecular Origin of the Glass Transition in Polyelectrolyte Assemblies.

Water plays a central role in the assembly and the dynamics of charged systems such as proteins, enzymes, DNA, and surfactants. Yet it remains a challenge to resolve how water affects relaxation at a molecular level, particularly for assemblies of oppositely charged macromolecules. Here, the molecular origin of water's influence on the glass transition is quantified for several charged macromolecular systems. It is revealed that the glass transition temperature (Tg) is controlled by the number of water molecules surrounding an oppositely charged polyelectrolyte-polyelectrolyte intrinsic ion pair as 1/Tg ∼ ln(nH2O/nintrinsic ion pair). This relationship is found to be "general", as it holds for two completely different types of charged systems (pH- and salt-sensitive) and for both polyelectrolyte complexes and polyelectrolyte multilayers, which are made by different paths. This suggests that water facilitates the relaxation of charged assemblies by reducing attractions between oppositely charged intrinsic ion pairs. This finding impacts current interpretations of relaxation dynamics in charged assemblies and points to water's important contribution at the molecular level.

No Time to Delay! Fiebig Stages and Referral in Acute HIV infection: Seattle Primary Infection Program Experience.

There has been increasing recognition of the importance of diagnosing individuals during the earliest stages of human immunodeficiency virus (HIV) infection. Sera from individuals referred to a primary HIV infection research program were screened using the IgG-sensitive Vironostika HIV-1 Microelisa System, IgG/IgM-sensitive GS HIV-1/HIV-2 Plus O antibody enzyme immunoassay (EIA), or Abbott ARCHITECT HIV antigen (Ag)/antibody (Ab) Combo assay and confirmed by the Bio-Rad Multispot and Western blot. A subset of participants was co-enrolled in a study designed to compare the ability of point-of-care tests to detect early infection. We calculated time within primary infection laboratory stages using actual observed transitions and with an expectation-maximization algorithm. Three hundred and sixty participants contributed data to this analysis. Of 123 persons referred with EIA-negative/RNA-positive test results (Fiebig stage I-II) or for concern for symptoms, 24 (20%) were still in stages I-II, and 99 (80%) were in stages III or later at their screening visit. Participants were estimated to spend a median of 13.5 days in stages I and II, 2.3 days in stage III, and 7.8 days in stage IV. OraQuick performed on oral fluids detected 53% of 17 participants in stage V. The durations of stages we observed are consistent with previous publications. Most persons referred for research no longer had acute infection at their first visit. Programs wishing to identify persons in the very earliest stages of infection need to expedite referrals or develop targeted screening programs.

Hydrogen-bonded polymer nanocomposites containing discrete layers of gold nanoparticles.

The ability to finely control the spatial location and relative concentration of a nanofiller within a polymer nanocomposite is desirable, especially when faced with fillers that are susceptible to aggregation. In the case of gold nanoparticles (AuNPs), spatial organization is of interest as it offers a means to harness optical and electrical properties, but well-defined placement of AuNPs within a polymer matrix is generally challenging because of phase separation. Here, we demonstrate for the first time the spray-assisted layer-by-layer assembly (LbL) of hydrogen-bonding polymer nanocomposites of poly(ethylene oxide) (PEO) and poly(methacrylic acid) (PMAA) containing discrete regions of AuNPs vertically positioned throughout the film structure. Analysis of the internal structure using cross-sectional transmission electron microscopy (TEM) imaging shows that the AuNP regions are clearly separated by "empty" regions of polymer with no drift or aggregation of the Au NPs during or after fabrication. A UV-vis spectroscopy study of the stimuli-responsive properties of the spray-assisted LbL nanocomposites shows the release of AuNPs as induced by elevating the environmental pH above the critical pH at which the PEO and PMAA hydrogen bonds are disrupted. We anticipate that this work enables the spatial organization of other nanofillers in stimuli-responsive hydrogen-bonding nanocomposites by spray-assisted LbL assembly.

Xylosandrus germanus (Coleoptera: Curculionidae: Scolytinae) Occurrence, Fungal Associations, and Management Trials in New York Apple Orchards.

Xylosandrus germanus (Blandford) has caused increasing damage in high-density New York apple orchards since 2013, resulting in tree decline and death. We documented their occurrence and timing in > 50 orchards using ethanol-baited traps from 2014 to 2016. First captures ranged from 48 to 83 degree days (base 10 °C) from 1 January. Captures were numerically higher at the orchard-woods interface than within the orchard interior, but differences were not significant in locations with lower populations. Control using insecticide trunk sprays was tested in potted, waterlogged apple trees placed in orchards and nurseries, and inside wooded areas adjacent to orchards. A verbenone repellent was used in combination with trunk sprays to improve control. Overall, insecticide sprays were inconsistent and marginal in preventing new infestations. Chlorpyrifos significantly reduced infestations versus lambda-cyhalothrin and untreated trees at one location in the 2015 orchard trials, and versus untreated trees at one location in the 2016 nursery trials, but otherwise performed no better than other treatments. The addition of verbenone to either the check or permethrin treatments resulted in significantly fewer attack sites containing brood at one orchard site in 2016. Chlorpyrifos, lambda-cyhalothrin, and permethrin significantly reduced the number of attack sites containing adults compared with untreated trees at one nursery trial location in 2016, but were otherwise ineffective in reducing numbers of trees in other locations and infestation categories. We found several fungal and bacterial species associated with X. germanus and its infestation of apples. These microbes likely play a minimal role in apple decline.

Performance of Determine Combo and other point-of-care HIV tests among Seattle MSM.

BACKGROUND AND OBJECTIVE: The rapid test study was a real-time comparison of point-of-care (POC) HIV tests to determine their abilities to detect early HIV infection. STUDY DESIGN: Men and transgender persons reporting sex with men in the prior year were recruited at the Public Health-Seattle & King County STD Clinic, Gay City Health Project, and University of Washington Primary Infection Clinic. Study tests included the OraQuick ADVANCE Rapid HIV-1/2 Antibody Test performed on oral fluids and tests performed on fingerstick whole blood specimens including OraQuick, Uni-Gold Recombigen HIV test, Determine HIV-1/2 Ag/Ab Combo, and INSTI HIV-1 Rapid Antibody Test. Specimens from subjects with negative results were sent for EIA and nucleic acid amplification testing. McNemar's exact tests compared the numbers of HIV-infected subjects detected. RESULTS: Between February 2010 and August 2014, there were 3438 study visits. Twenty-four subjects had discordant POC results with at least one reactive and one non-reactive test, including one subject with a reactive Determine p24 antigen. OraQuick performed on oral fluids identified fewer persons compared to all fingerstick tests. OraQuick performed on fingerstick whole blood detected fewer persons compared to the Determine Combo antibody component (p=.008) and Combo overall (p=.004), and there was a trend when compared to INSTI (p=.06). The Determine Combo specificity was 98.99%. CONCLUSIONS: As reported by others, Determine Combo underperforms compared to laboratory-based testing, but it did detect one acute infection. If these results are validated, the specificity of Determine Combo may limit its usefulness in populations with lower HIV incidence.

Relative accuracy of serum, whole blood, and oral fluid HIV tests among Seattle men who have sex with men.

BACKGROUND: Point-of-care (POC) rapid HIV tests have sensitivity during the "window period" comparable only to earliest generation EIAs. To date, it is unclear whether any POC test performs significantly better than others. OBJECTIVE: Compare abilities of POC tests to detect early infection in real time. STUDY DESIGN: Men who have sex with men (MSM) were recruited into a prospective, cross-sectional study at two HIV testing sites and a research clinic. Procedures compared four POC tests: one performed on oral fluids and three on fingerstick whole blood specimens. Specimens from participants with negative POC results were tested by EIA and pooled nucleic acid amplification testing (NAAT). McNemar's exact tests compared numbers of HIV-infected participants detected. RESULTS: Between February 2010 and May 2013, 104 men tested HIV-positive during 2479 visits. Eighty-two participants had concordant reactive POC results, 3 participants had concordant non-reactive POC tests but reactive EIAs, and 8 participants had acute infection. Of 12 participants with discordant POC results, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test performed on oral fluids identified fewer infections than OraQuick performed on fingerstick (p = .005), Uni-Gold Recombigen HIV test (p = .01), and determine HIV-1/2 Ag/Ab combo (p = .005). CONCLUSIONS: These data confirm that oral fluid POC testing detects fewer infections than other methods and is best reserved for circumstances precluding fingerstick or venipuncture. Regardless of specimen type, POC tests failed to identify many HIV-infected MSM in Seattle. In populations with high HIV incidence, the currently approved POC antibody tests are inadequate unless supplemented with p24 antigen tests or NAAT.