Orientation anisotropies in macaque visual areas.

In mammals, a larger number of neurons in V1 are devoted to cardinal (horizontal and vertical) orientations than to oblique orientations. However, electrophysiological results from the macaque monkey visual cortex are controversial. Both isotropic and anisotropic orientation distributions have been reported. It is also unclear whether different visual areas along the visual hierarchy have different orientation anisotropies. We analyzed orientation maps in a large set of intrinsic signal optical imaging data and found that both V1 and V4 exhibited significant orientation anisotropies. However, their overrepresented orientations were very different: in V1, both cardinal and radial orientations were overrepresented, while in V4, only cardinal bias was presented. These findings suggest that different cortical areas have evolved to emphasize different features that are suitable for their functional purposes, a factor that needs to be considered when efforts are made to explain the relationships between the visual environment and the cortical representation and between the cortical representation and visual perception.

Selection Bias Requires Selection: The Case of Collider Stratification Bias.

In epidemiology, collider stratification bias, the bias resulting from conditioning on a common effect of two causes, is oftentimes considered a type of selection bias, regardless of the conditioning methods employed. In this commentary, we distinguish between two types of collider stratification bias: collider restriction bias due to restricting to one level of a collider (or a descendant of a collider) and collider adjustment bias through inclusion of a collider (or a descendant of a collider) in a regression model. We argue that categorizing collider adjustment bias as a form of selection bias may lead to semantic confusion, as adjustment for a collider in a regression model does not involve selecting a sample for analysis. Instead, we propose that collider adjustment bias can be better viewed as a type of overadjustment bias. We further provide two distinct causal diagram structures to distinguish collider restriction bias and collider adjustment bias. We hope that such a terminological distinction can facilitate easier and clearer communication.

The Evolution of Selection Bias in the Recent Epidemiologic Literature-A Selective Overview.

Selection bias has long been central in methodological discussions across epidemiology and other fields. In epidemiology, the concept of selection bias has been continually evolving over time. In this issue of the Journal, Mathur and Shpitser (Am J Epidemiol. XXXX;XXX(XX):XXXX-XXXX) present simple graphical rules for using a Single World Intervention Graph (SWIG) to assess the presence of selection bias when estimating treatment effects in both the general population and a selected sample. Notably, the authors examine the setting in which the treatment affects selection, an issue not well-addressed in the existing literature on selection bias. To place the work by Mathur and Shpitser in context, we review the evolution of the concept of selection bias in epidemiology, with a primary focus on the developments in the last 20-30 years since the introduction of causal directed acyclic graphs (DAGs) to epidemiologic research.

Synergistic interaction between pay-it-forward incentives and recreational drug use on hepatitis B virus and hepatitis C virus testing among men who have sex with men in China.

OBJECTIVES: Pay-it-forward incentives effectively promote hepatitis B virus (HBV) and hepatitis C virus (HCV) testing among men who have sex with men (MSM) by offering free testing and donation opportunities. This study aims to explore the interaction between pay-it-forward incentives and recreational drug use on HBV and HCV testing uptake among Chinese MSM. METHODS: We pooled data from two pay-it-forward studies that aimed to promote dual HBV and HCV testing among MSM in Jiangsu, China. We explored factors associated with hepatitis testing uptake in the two study groups and examined the interaction between pay-it-forward incentives and recreational drug use on hepatitis testing uptake. RESULTS: Overall, 511 MSM participated in these two studies, with 265 participants in the pay-it-forward incentives group and 246 participants in the standard-of-care group. Among these participants, 59.3% in the pay-it-forward incentive group and 24.8% in the standard-of-care group received dual HBV and HCV testing, respectively. In the pay-it-forward incentives group, participants who used recreational drugs in the past 12 months (adjusted OR (AOR)=1.83, 95% CI 1.09 to 3.06) were more likely to receive dual HBV and HCV testing, compared with those who never used recreational drugs, whereas in the standard-of-care group, those who used recreational drugs were less likely to receive dual HBC and HCV testing (AOR=0.38, 95% CI 0.18 to 0.78). MSM with higher community connectedness (AOR=1.10, 95% CI 1.00 to 1.21) were also more likely to receive hepatitis testing with pay-it-forward incentives. There was a synergistic interaction on both the multiplicative (ratio of ORs=4.83, 95% CI 1.98 to 11.7) and additive scales (the relative excess risk of interaction=2.97, 95% CI 0.56 to 5.38) of pay-it-forward incentives and recreational drug use behaviours on dual HBV and HCV testing uptake among MSM. CONCLUSION: Pay-it-forward incentives may be particularly useful in promoting hepatitis testing among MSM who use recreational drugs.

Reconstruction and analysis of transient evolution images of laser-produced plasma plumes.

We introduce a method for the analysis and simulation of transient images of laser-produced plasma (LPP) plumes. This method comprises three steps: (i) calculating the two-dimensional distribution of plasma parameters using a radiation hydrodynamics model, (ii) constructing radiation paths through ray tracing, and (iii) solving the radiation transport equation along these paths. In our simulations, we have meticulously considered factors that could influence the imaging results, including the quantum efficiency to different radiation wavelengths, the imaging lens' transmittance, the target surface's reflectivity, and the absorption, emission, and scattering quantum effect of the detector processes occurring in the plasma. We applied this method to analyze and simulate the transient images of aluminum plasma plumes in a background air environment at a pressure of 2000 Pa. The results demonstrate that our method not only produces simulated images that align with experimental results but also provides a reliable distribution of plasma state parameters and clearly identifies the ion species radiating in different bands. Given its capability in transient image reconstruction and its adaptability as a tool for spectral simulation and analysis of LPPs, we believe this method holds significant potential for spectral diagnostics in fields such as laser-induced breakdown spectroscopy, extreme ultraviolet lithography sources, and high-energy-density physics, among others.

Mesoscale functional connectivity in macaque visual areas.

Studies of resting-state functional connectivity (rsFC) have provided rich insights into the structures and functions of the human brain. However, most rsFC studies have focused on large-scale brain connectivity. To explore rsFC at a finer scale, we used intrinsic signal optical imaging to image the ongoing activity of the anesthetized macaque visual cortex. Differential signals from functional domains were used to quantify network-specific fluctuations. In 30-60 min resting-state imaging, a series of coherent activation patterns were observed in all three visual areas we examined (V1, V2, and V4). These patterns matched the known functional maps (ocular dominance, orientation, color) obtained in visual stimulation conditions. These functional connectivity (FC) networks fluctuated independently over time and exhibited similar temporal characteristics. Coherent fluctuations, however, were observed from orientation FC networks in different areas and even across two hemispheres. Thus, FC in the macaque visual cortex was fully mapped both on a fine scale and over a long range. Hemodynamic signals can be used to explore mesoscale rsFC in a submillimeter resolution.

Optimizing Treatment for Human Immunodeficiency Virus to Improve Clinical Outcomes Using Precision Medicine.

In first-line antiretroviral therapy (ART) for human immunodeficiency virus (HIV) treatment, some subgroups of patients may respond better to an efavirenz-based regimen than an integrase strand transfer inhibitor (InSTI)-based regimen, or vice versa, due to patient characteristics modifying treatment effects. Using data based on nearly 16,000 patients from the North American AIDS Cohort Collaboration on Research and Design from 2009-2016, statistical methods for precision medicine were employed to estimate an optimal treatment rule that minimizes the 5-year risk of the composite outcome of acquired immune deficiency syndrome (AIDS)-defining illnesses, serious non-AIDS events, and all-cause mortality. The treatment rules considered were functions that recommend either an efavirenz- or InSTI-based regimen conditional on baseline patient characteristics such as demographic information, laboratory results, and health history. The estimated 5-year risk under the estimated optimal treatment rule was 10.0% (95% confidence interval (CI): 8.6, 11.3), corresponding to an absolute risk reduction of 2.3% (95% CI: 0.9, 3.8) when compared with recommending an efavirenz-based regimen for all patients and 2.6% (95% CI: 1.0, 4.2) when compared with recommending an InSTI-based regimen for all. Tailoring ART to individual patient characteristics may reduce 5-year risk of the composite outcome compared with assigning all patients the same drug regimen.

Real optical imaging simulation of laser-produced aluminum plasmas.

We developed a post-processing optical imaging model based on two-dimensional axisymmetric radiation hydrodynamics. Simulation and program benchmarks were performed using laser-produced Al plasma optical images obtained via transient imaging. The emission profiles of a laser-produced Al plasma plume in air at atmospheric pressure were reproduced, and the influence of plasma state parameters on radiation characteristics were clarified. In this model, the radiation transport equation is solved on the real optical path, which is mainly used to study the radiation of luminescent particles during plasma expansion. The model outputs consist of the electron temperature, particle density, charge distribution, absorption coefficient, and corresponding spatio-temporal evolution of the optical radiation profile. The model helps with understanding element detection and quantitative analysis of laser-induced breakdown spectroscopy.

Mechanical Stress Modulation of Resistance in MoS2 Junctions.

Strain engineering is a powerful strategy to control the physical properties of material-enabling devices with enhanced functionality and improved performance. Here, we investigate a modulation of the transport behavior of the two-dimensional MoS2 junctions under the mechanical stress induced by a tip of an atomic force microscope (AFM). We show that the junction resistance can be reversibly tuned by up to 4 orders of magnitude by altering a tip-induced force. Analysis of the stress-induced evolution of the I-V characteristics indicates a combined effect of the tip-induced strain and strain gradient on the energy barrier height and profile. In addition, we show that the tip-generated flexoelectric effect leads to significant enhancement of the photovoltaic effect in the MoS2 junctions. A combination of the optical and mechanical stimuli facilitates reversible photomechanical tuning of resistance of the narrow-band 2D semiconductors and development of devices with an enhanced photovoltaic response.

Toward a Clearer Definition of Selection Bias When Estimating Causal Effects.

Selection bias remains a subject of controversy. Existing definitions of selection bias are ambiguous. To improve communication and the conduct of epidemiologic research focused on estimating causal effects, we propose to unify the various existing definitions of selection bias in the literature by considering any bias away from the true causal effect in the referent population (the population before the selection process), due to selecting the sample from the referent population, as selection bias. Given this unified definition, selection bias can be further categorized into two broad types: type 1 selection bias owing to restricting to one or more level(s) of a collider (or a descendant of a collider) and type 2 selection bias owing to restricting to one or more level(s) of an effect measure modifier. To aid in explaining these two types-which can co-occur-we start by reviewing the concepts of the target population, the study sample, and the analytic sample. Then, we illustrate both types of selection bias using causal diagrams. In addition, we explore the differences between these two types of selection bias, and describe methods to minimize selection bias. Finally, we use an example of "M-bias" to demonstrate the advantage of classifying selection bias into these two types.

Clinical Effectiveness of Integrase Strand Transfer Inhibitor-Based Antiretroviral Regimens Among Adults With Human Immunodeficiency Virus: A Collaboration of Cohort Studies in the United States and Canada.

BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes. METHODS: We included participants from clinical cohorts in the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen, containing either InSTI (ie, raltegravir, dolutegravir, and elvitegravir-cobicistat) or efavirenz (EFV) as an active comparator, between 2009 and 2016. We estimated observational analogs of 6-year intention-to-treat and per-protocol risks, risk differences (RDs), and hazard ratios (HRs) for the composite outcome of AIDS, acute myocardial infarction, stroke, end-stage renal disease, end-stage liver disease, or death. RESULTS: Of 15 993 participants, 5824 (36%) initiated an InSTI-based and 10 169 (64%) initiated an EFV-based regimen. During the 6-year follow-up, 440 in the InSTI group and 1097 in the EFV group incurred the composite outcome. The estimated 6-year intention-to-treat risks were 14.6% and 14.3% for the InSTI and EFV groups, respectively, corresponding to a RD of 0.3% (95% confidence interval, -2.7% to 3.3%) and a HR of 1.08 (.97-1.19); the estimated 6-year per-protocol risks were 12.2% for the InSTI group and 11.9% for the EFV group, corresponding to a RD of 0.3% (-3.0% to 3.7%) and a HR of 1.09 (.96-1.25). CONCLUSIONS: InSTI- and EFV-based initial ART regimens had similar 6-year composite clinical outcomes. The risk of adverse clinical outcomes remains substantial even when initiating modern ART.

Ferroelectric Domain Wall Memristor.

A domain wall-enabled memristor is created, in thin film lithium niobate capacitors, which shows up to twelve orders of magnitude variation in resistance. Such dramatic changes are caused by the injection of strongly inclined conducting ferroelectric domain walls, which provide conduits for current flow between electrodes. Varying the magnitude of the applied electric-field pulse, used to induce switching, alters the extent to which polarization reversal occurs; this systematically changes the density of the injected conducting domain walls in the ferroelectric layer and hence the resistivity of the capacitor structure as a whole. Hundreds of distinct conductance states can be produced, with current maxima achieved around the coercive voltage, where domain wall density is greatest, and minima associated with the almost fully switched ferroelectric (few domain walls). Significantly, this "domain wall memristor" demonstrates a plasticity effect: when a succession of voltage pulses of constant magnitude is applied, the resistance changes. Resistance plasticity opens the way for the domain wall memristor to be considered for artificial synapse applications in neuromorphic circuits.

An Orientation Map for Disparity-Defined Edges in Area V4.

Binocular disparity information is an important source of 3D perception. Neurons sensitive to binocular disparity are found in almost all major visual areas in nonhuman primates. In area V4, disparity processes are suggested for the purposes of 3D-shape representation and fine disparity perception. However, whether neurons in V4 are sensitive to disparity-defined edges used in shape representation is not clear. Additionally, a functional organization for disparity edges has not been demonstrated so far. With intrinsic signal optical imaging, we studied functional organization for disparity edges in the monkey visual areas V1, V2, and V4. We found that there is an orientation map in V4 activated by edges purely defined by binocular disparity. This map is consistent with the orientation map obtained with regular luminance-defined edges, indicating a cue-invariant edge representation in this area. In contrast, such a map is much weaker in V2 and totally absent in V1. These findings reveal a hierarchical processing of 3D shape along the ventral pathway and the important role that V4 plays in shape-from-disparity detection.

Factors influencing caspofungin plasma concentrations in kidney transplant patients with high incidence of invasive fungal infections.

WHAT IS KNOWN AND OBJECTIVE: Caspofungin is commonly used in kidney transplant patients for prophylaxis or treatment of invasive fungal infections (IFIs) caused by Candida spp. and Aspergillus spp. Factors such as concomitant medications, co-morbidity and rejection often cause caspofungin pharmacokinetic parameters alterations in kidney transplant patients. Here, we aimed to investigate factors influencing caspofungin plasma concentrations and evaluate its prophylaxis and treatment efficiency for IFIs in kidney transplant patients. METHODS: The prophylaxis and treatment efficiency of caspofungin for IFIs were assessed in 164 kidney transplant patients in the study. Six hundred and fifty-two caspofungin trough concentrations (Cmin ) from the 164 patients were monitored by the liquid chromatography-tandem mass spectrometry method. Basic demographic variables, baseline disease, surgery, rejection, indwelling catheter, coinfection, concomitant medication and other caspofungin-related factors were collected. Univariate and multivariate analyses were used to assess factors influencing caspofungin plasma concentrations. RESULTS AND DISCUSSION: The success rates were 94.96% (132/139) for caspofungin prevention and 80% (20/25) for caspofungin for IFIs. Caspofungin Cmin in the kidney recipients varied largely compared with healthy volunteers (0.10-12.25 mg/L vs. 1.12-1.78 mg/L). Caspofungin Cmin significantly increased in patients with continuous renal replacement therapy before transplantation (P = .001), concomitant medication of cyclosporine A (CsA, P = .009), ALB concentration of > 30 g/L (P = .019). WHAT IS NEW AND CONCLUSION: This is an uncontrolled observational study of caspofungin as prophylaxis or treatment for IFIs in kidney transplant patients. Caspofungin could be an effective and well-tolerated option for antifungal prophylaxis and treatment in kidney transplant patients, and a number of factors could influence caspofungin Cmin in these patients.

Solving visual correspondence between the two eyes via domain-based population encoding in nonhuman primates.

Stereoscopic vision depends on correct matching of corresponding features between the two eyes. It is unclear where the brain solves this binocular correspondence problem. Although our visual system is able to make correct global matches, there are many possible false matches between any two images. Here, we use optical imaging data of binocular disparity response in the visual cortex of awake and anesthetized monkeys to demonstrate that the second visual cortical area (V2) is the first cortical stage that correctly discards false matches and robustly encodes correct matches. Our findings indicate that a key transformation for achieving depth perception lies in early stages of extrastriate visual cortex and is achieved by population coding.

Inflammation and Risk of Depression in HIV: Prospective Findings From the Multicenter AIDS Cohort Study.

Studies suggest that inflammation might be involved in the pathogenesis of depression. Individuals with human immunodeficiency virus (HIV) have a higher risk of depression and elevated inflammatory profiles. Despite this, research on the link between inflammation and depression among this high-risk population is limited. We examined a sample of men who have sex with men from the Multicenter AIDS Cohort Study in prospective analyses of the association between inflammation and clinically relevant depression symptoms, defined as scores >20 on Center for Epidemiological Studies Depression Scale. We included 1,727 participants who contributed 9,287 person-visits from 1984 to 2010 (8,218 with HIV (HIV+) and 1,069 without (HIV-)). Exploratory factor analysis (EFA) was used to characterize underlying inflammatory processes from 19 immune markers. Logistic regression with generalized estimating equations was used to evaluate associations between inflammatory processes and depressive symptoms stratified by HIV serostatus. Three EFA-identified inflammatory processes (EIPs) were identified. EIP-1 scores-described by soluble tumor necrosis factor receptor 2 (sTNF-R2), soluble interleukin-2 receptor α (sIL-2Rα), sCD27, B-cell activating factor, interferon γ-induced protein 10 (IP-10), soluble interleukin-6 receptor (sIL-6R), sCD14, and sGP130-were significantly associated with 9% higher odds of depressive symptoms in HIV+ participants (odds ratio = 1.09; 95% confidence interval: 1.03, 1.16) and 33% higher odds in HIV- participants (odds ratio = 1.33; 95% confidence interval: 1.09, 1.61). Findings suggest that immune activation might be involved in depression risk among both HIV+ and HIV- men who have sex with men.

Recalling, Sharing and Participating in a Social Media Intervention Promoting HIV Testing: A Longitudinal Analysis of HIV Testing Among MSM in China.

Social media interventions may enhance HIV services among key populations, including men who have sex with men (MSM). This longitudinal analysis examined the effect of recalling, sharing, and participating in different components of a social media intervention on HIV testing among MSM. The social media intervention included six images/texts and information about an online local community contest to promote testing. Of the 1033 men, they recalled a mean of 2.7 out of six images and shared an average of one image online. 34.5% of men recalled information on the online local community contest and engaged in a mean of 1.3 contest. Recalling images/texts (aOR = 1.13, 95% CI 1.02-1.25) and recalling a local contest (aOR = 1.59, 95% CI 1.13-1.24) were associated with facility-based HIV testing. This study has implications for the development and evaluation of social media interventions to promote HIV testing.

What happens after HIV self-testing? Results from a longitudinal cohort of Chinese men who have sex with men.

BACKGROUND: HIV self-testing (HIVST) is a promising approach to expand HIV testing. HIVST is a process in which a person performs an HIV test and interprets the result. Negative HIVST results may encourage men who have sex with men (MSM) to use HIV prevention services. The objective of this study was to examine behaviors (e.g., facility-based HIV testing, condom use) after a negative HIVST test result among Chinese MSM. METHODS: We collected data from MSM in eight Chinese cities over a 12-month period. This is a secondary analysis of longitudinal cohort data collected as part of an intervention trial to increase HIV testing. Men completed a survey that described sociodemographic information, sexual behaviors, HIV self-testing, and facility-based HIV testing. Men who completed at least one follow-up survey were included in this analysis. Generalized linear mixed models were used to evaluate whether HIVST increased subsequent facility-based HIV testing and consistent condom use. RESULTS: We included 1219 men. Most men (78.7%) were under 30 years old and had never been married (87.0%). 755 (61.9%) men tested for HIV and 593 (49.3%) men self-tested during the study period. At baseline, among men who had never been tested for HIV, 44.9% (314/699) initiated HIVST during the study period. HIVST was associated with subsequent facility-based testing (aOR of 1.87, 95% CI: 1.47-2.37). HIVST was also associated with subsequent consistent condom use (aOR = 1.53, 95% CI: 1.13-2.06). CONCLUSION: HIVST was associated with subsequent facility-based HIV testing and consistent condom use. HIVST may enhance uptake of related HIV prevention services at facilities, suggesting the need for more implementation research.

Generalizing the per-protocol treatment effect: The case of ACTG A5095.

BACKGROUND: Intention-to-treat comparisons of randomized trials provide asymptotically consistent estimators of the effect of treatment assignment, without regard to compliance. However, decision makers often wish to know the effect of a per-protocol comparison. Moreover, decision makers may also wish to know the effect of treatment assignment or treatment protocol in a user-specified target population other than the sample in which the trial was fielded. Here, we aimed to generalize results from the ACTG A5095 trial to the US recently HIV-diagnosed target population. METHODS: We first replicated the published conventional intention-to-treat estimate (2-year risk difference and hazard ratio) comparing a four-drug antiretroviral regimen to a three-drug regimen in the A5095 trial. We then estimated the intention-to-treat effect that accounted for informative dropout and the per-protocol effect that additionally accounted for protocol deviations by constructing inverse probability weights. Furthermore, we employed inverse odds of sampling weights to generalize both intention-to-treat and per-protocol effects to a target population comprising US individuals with HIV diagnosed during 2008-2014. RESULTS: Of 761 subjects in the analysis, 82 dropouts (36 in the three-drug arm and 46 in the four-drug arm) and 59 protocol deviations (25 in the three-drug arm and 34 in the four-drug arm) occurred during the first 2 years of follow-up. A total of 169 subjects incurred virologic failure or death. The 2-year risks were similar both in the trial and in the US HIV-diagnosed target population for estimates from the conventional intention-to-treat, dropout-weighted intention-to-treat, and per-protocol analyses. In the US target population, the 2-year conventional intention-to-treat risk difference (unit: %) for virologic failure or death comparing the four-drug arm to the three-drug arm was -0.4 (95% confidence interval: -6.2, 5.1), while the hazard ratio was 0.97 (95% confidence interval: 0.70, 1.34); the 2-year risk difference was -0.9 (95% confidence interval: -6.9, 5.3) for the dropout-weighted intention-to-treat comparison (hazard ratio = 0.95, 95% confidence interval: 0.68, 1.32) and -0.7 (95% confidence interval: -6.7, 5.5) for the per-protocol comparison (hazard ratio = 0.96, 95% confidence interval: 0.69, 1.34). CONCLUSION: No benefit of four-drug antiretroviral regimen over three-drug regimen was found from the conventional intention-to-treat, dropout-weighted intention-to-treat or per-protocol estimates in the trial sample or target population.

Spatial structure of neuronal receptive field in awake monkey secondary visual cortex (V2).

Visual processing depends critically on the receptive field (RF) properties of visual neurons. However, comprehensive characterization of RFs beyond the primary visual cortex (V1) remains a challenge. Here we report fine RF structures in secondary visual cortex (V2) of awake macaque monkeys, identified through a projection pursuit regression analysis of neuronal responses to natural images. We found that V2 RFs could be broadly classified as V1-like (typical Gabor-shaped subunits), ultralong (subunits with high aspect ratios), or complex-shaped (subunits with multiple oriented components). Furthermore, single-unit recordings from functional domains identified by intrinsic optical imaging showed that neurons with ultralong RFs were primarily localized within pale stripes, whereas neurons with complex-shaped RFs were more concentrated in thin stripes. Thus, by combining single-unit recording with optical imaging and a computational approach, we identified RF subunits underlying spatial feature selectivity of V2 neurons and demonstrated the functional organization of these RF properties.