Low-Level Anorectal HIV Shedding despite Effective Antiretroviral Therapy Is Not Driven by Mucosal Inflammation.

Although antiretroviral treatment (ART) suppresses HIV RNA in blood and prevents transmission, low-level anorectal HIV RNA shedding persists in some ART-treated men who have sex with men. We collected anorectal biopsies and swabs from 55 men who have sex with men on effective ART, hypothesizing that anorectal shedding would be linked to microbiota-driven mucosal T cell activation. Lymphocytes were assessed by flow cytometry, soluble immune factors by multiplex immunoassay, neutrophils and epithelial integrity by immunofluorescence microscopy, and the anorectal microbiome by quantitative PCR and 16S rRNA gene sequencing. Unexpectedly, we found no evidence that anorectal HIV shedding was associated with the parameters of mucosal inflammation, including T cell activation, inflammatory cytokines, the density of neutrophils, or epithelial integrity. Moreover, the anorectal bacterial load was actually lower in the shedding group, with no major differences in bacterial composition. Instead, the strongest mucosal immune correlates of HIV shedding were an increase in central memory cell frequency and Ki67 expression as well as higher concentrations of the cytokine IL-7 in anorectal secretions. Anorectal HIV RNA shedding during effective ART was not driven by local inflammation; the associations seen with local homeostatic T cell proliferation will require further confirmation.

Anal dysplasia and HIV shedding in ART-treated men.

OBJECTIVES: Anal human papillomavirus (HPV) infection is highly prevalent among men who have sex with men (MSM). HPV-associated anal dysplasia has been linked with anal HIV RNA shedding despite antiretroviral therapy (ART). Since mucosal HIV levels are a key determinant of sexual transmission of the virus, this would have important public health implications. Therefore, we assessed the association between anal dysplasia and HIV shedding in ART-treated MSM from Toronto, Canada. METHODS: In 54 HIV-infected men on effective ART, we assessed anal HIV RNA shedding by PCR, HPV infection by microsphere-based genotyping and anal dysplasia by high-resolution anoscopy. All participants were enrolled between May 2017 and October 2018. RESULTS: The median duration of ART at the time of study enrolment was 18 years, with most participants being on an integrase inhibitor-based ART regimen. Low-level anal HIV RNA shedding was present in 15/54 (27.8%) participants. Neither the detection of shedding nor the level of HIV RNA was associated with anal dysplasia, HPV infection or antiretroviral regimen. CONCLUSIONS: HPV-associated anal dysplasia was not associated with anal HIV RNA shedding in this relatively small cohort of men on effective ART. While anal HIV RNA was detected more often than anticipated, shedding was low level and unlikely to cause HIV transmission. However, the immunological drivers of anal HIV RNA shedding in ART-treated individuals may merit further study.

Holographic microinformation hiding.

We propose a holographic microinformation hiding scheme in which the embedding information to be embedded is small and imperceptible to the human eyes. This scheme converts the embedding information into a complex amplitude via scaled diffraction. The complex amplitude of the reduced embedding information is added to the complex amplitude of the host image, followed by conversion to a hologram. The reduced embedded information is inconspicuous from the hologram during the reconstruction process; however, the reduction leads to the degradation of the embedded image quality. Therefore, to improve the quality of the embedded image quality, we employ iterative optimization and the time averaging effect of multiple holograms.

Convolutional neural network-based data page classification for holographic memory.

We propose a deep-learning-based classification of data pages used in holographic memory. We numerically investigated the classification performance of a conventional multilayer perceptron (MLP) and a deep neural network, under the condition that reconstructed page data are contaminated by some noise and are randomly laterally shifted. When data pages are randomly laterally shifted, the MLP was found to have a classification accuracy of 93.02%, whereas the deep neural network was able to classify data pages at an accuracy of 99.98%. The accuracy of the deep neural network is 2 orders of magnitude better than the MLP.

Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

BACKGROUND: High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. OBJECTIVES: The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at an outpatient clinic at a tertiary care center in Toronto. PATIENTS: Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. INTERVENTION: All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. MAIN OUTCOME MEASURES: We measured the incidence of anal cancer per 100 person-years of follow-up. RESULTS: Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. LIMITATIONS: There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. CONCLUSIONS: HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

Color computer-generated hologram generation using the random phase-free method and color space conversion.

We propose two calculation methods of generating color computer-generated holograms (CGHs) with the random phase-free method and color space conversion in order to improve the image quality and accelerate the calculation. The random phase-free method improves the image quality in monochrome CGH, but it is not performed in color CGH. We first aimed to improve the image quality of color CGH using the random phase-free method and then to accelerate the color CGH generation with a combination of the random phase-free method and color space conversion method, which accelerates the color CGH calculation due to down-sampling of the color components converted by color space conversion. To overcome the problem of image quality degradation that occurs due to the down-sampling of random phases, the combination of the random phase-free method and color space conversion method improves the quality of reconstructed images and accelerates the color CGH calculation. We demonstrated the effectiveness of the proposed method in simulation, and in this paper discuss its application to lensless zoomable holographic projection.

Random phase-free kinoform for large objects.

We propose a random phase-free kinoform for large objects. When not using the random phase in kinoform calculation, the reconstructed images from the kinoform are heavy degraded, like edge-only preserved images. In addition, the kinoform cannot record an entire object that exceeds the kinoform size because the object light does not widely spread. In order to avoid this degradation and to widely spread the object light, the random phase is applied to the kinoform calculation; however, the reconstructed image is contaminated by speckle noise. In this paper, we overcome this problem by using our random phase-free method and error diffusion method.

The psychological impact of being screened for anal cancer in HIV-infected men who have sex with men.

BACKGROUND: Anal cancer screening may be considered in HIV-infected men who have sex with men because they are at increased risk. Cancer screening can provoke anxiety, which may lead to poorer screening compliance. OBJECTIVE: This study aimed to measure the psychological consequences of anal cancer screening in HIV-infected men who have sex with men. DESIGN: This investigation is a prospective cohort study. SETTING: This study was conducted in primary and tertiary care HIV clinics in Toronto, Canada. PATIENTS: One hundred four HIV-infected men who have sex with men were studied. MAIN OUTCOME MEASURES: : Psychological impact was measured at 4 time points (before screening, after screening, after receiving results, and before follow-up) using the Impact of Events Scale, the Illness Intrusiveness Ratings Scale, and the Psychological Consequences Questionnaire. RESULTS: Median age was 44, 77% were receiving antiretroviral therapy, and 11% had high-grade anal dysplasia (anal intraepithelial neoplasia 2/3). Fifteen to 32% of the patients reported high levels of negative psychological consequences across the 4 time points; the highest levels occurred at time 2. Higher HIV symptom count and baseline level of negative impact were significantly associated with higher Impact of Events scores, whereas younger age and a higher baseline level of negative impact were significantly associated with higher scores with use of the Illness Intrusiveness Ratings Scale. CONCLUSIONS: Anal cancer screening is not associated with greater adverse psychological impact in most HIV-infected men who have sex with men. Younger patients, those with more HIV-related symptoms and greater baseline psychological distress, are at risk for increased psychological distress during screening.

Travel patterns and risk behaviour of HIV-positive people travelling internationally.

BACKGROUND: International travel is associated with an increased risk of enteric, vector-borne, sexually transmitted and blood-borne infections. These risks are even higher among immunocompromised people, such as those with HIV infection. We conducted a study to determine HIV-positive people's travel patterns and risk behaviours while abroad. METHODS: We conducted an anonymous survey of HIV-positive people attending an HIV clinic in a tertiary care hospital in Toronto about their travel activities and pretravel precautions as well as their burden of illness and risk exposure during travel. We compared the characteristics of respondents who had travelled outside Canada and the United States (international travellers) with those of respondents who had not travelled internationally. RESULTS: Of 290 HIV-positive people who participated in the study, 133 (45.9%) indicated that they had travelled internationally in the 5 years before the survey. These people were predominantly men (93.2%) and well educated (60.0% had a university level education), and they had travelled mostly for personal reasons (89.5%) on trips that lasted 3.6 weeks on average. Only 58 (43.6%) sought health advice before travelling, and only 17 (12.8%) sought advice from a travel clinic. Five (3.8%) had received live vaccines before travel, and 9 (6.8%) had taken malaria chemoprophylaxis. Of the 119 international travellers who were taking antiretroviral therapy; 35 (29.4%) reported either discontinuing their medications or being poorly compliant with the therapy while travelling. Thirty-one (23.3%) of the 133 international travellers reported having had casual sexual activity with new partners while travelling, and only 18 (58.1%) of them reported always using a condom. Twenty-one (15.8%) of the 133 reported having had risky exposure to sharps. Twenty-four (18.0%) said they had become ill enough while travelling to require medical attention. INTERPRETATION: Only one-fifth of HIV-positive people surveyed who travelled internationally sought advice from a health professional before their trip. Their travel was associated with poor adherence to antiretroviral therapy, risky sexual practices and risky exposure to sharps.

A new wavelet in the multifocal electroretinogram, probably originating from ganglion cells.

PURPOSE: To report the properties of a newly detected positive wavelet on the descending limb of P1 of the first-order kernel of the human multifocal electroretinogram (mfERG). METHODS: Twenty eyes of 20 normal individuals, ages 21 to 29 years (mean, 25.6) and nine eyes of 6 patients with optic neuritis ages 5 to 38 years (mean, 17.3) were studied. mfERGs were recorded with a visual evoked response imaging system with the number of stimulus elements set at 37. The stimulus frequency was changed from 75 to 37, 18, 9.4, 4.7, and 2.3 Hz, and the contrast of the stimuli was lowered to 50%. RESULTS: In normal eyes, a positive wavelet appeared on the descending limb of P1 of the first-order kernel of the mfERG when the stimulus frequency was reduced from 75 to 18 Hz. The wavelet had a mean amplitude of 4.2 nV/deg(2) and a mean implicit time of 34 ms at 18 Hz. When the stimulus frequency was reduced further to 2.3 Hz, the amplitude of the wavelet increased significantly (P < 0.05) compared with that at 18 Hz. The amplitudes of the wavelet elicited from the nasal side of the retina were significantly larger (P < 0.05) than those from the temporal side and decreased significantly (P < 0.05) with increasing distance from the optic disc. The wavelet was not present in any of the patients with newly diagnosed optic neuritis, but reappeared with recovery from the disease. The recovery of the wavelet correlated significantly with the recovery of visual acuity and of central critical fusion frequency. CONCLUSIONS: The amplitude of the wavelet on the descending limb of P1 of the first-order kernel of the mfERG was dependent on the stimulus frequency and the retinal locus. The wavelet was not present in the mfERGs recorded in patients with optic neuritis, but returned with recovery from the disease. These findings suggest that the neural activity of the ganglion cells give rise to this wavelet.

Decrease of blue cone sensitivity in acute idiopathic blind spot enlargement syndrome.

PURPOSE: To determine the sensitivity of the blue cone system by static perimetry in patients with unilateral acute idiopathic blind spot enlargement (AIBSE) syndrome. DESIGN: Observational case series. METHODS: Four patients with AIBSE syndrome, aged 16 to 30 years, were studied. Diagnosis of the AIBSE syndrome was based on clinical findings including an enlarged blind spot without corresponding ophthalmoscopic changes of the ocular fundus and with depressed multifocal electoretinograms. The visual sensitivity and mean deviations (MD) were measured by white-on-white (W/W) and blue-on-yellow (B/Y) automated perimetry. RESULTS: The average difference in the MD between the affected and unaffected eyes was 4.87 +/- 1.51 dB and 13.65 +/- 4.19 dB for W/W and B/Y perimetries, respectively. The difference between the two groups of eyes was significantly greater for B/Y perimetry than that for W/W perimetry (P =.01). CONCLUSIONS: Our results suggest that the decrease of blue cone sensitivity is diffusely present over the retina in eyes with AIBSE syndrome. We recommend B/Y perimetry as a sensitive measure to detect retinal dysfunction that is not detected by W/W perimetry.

Travel patterns and risk behavior in solid organ transplant recipients.

BACKGROUND: International travel is associated with an increased risk of enteric, vector-borne and bloodborne infections. The risk of acquiring travel-related illness is higher in those who are immunocompromised. However, little is known about travel practices and risk behaviors in transplant recipients who travel. We herein profile transplant recipients who travel, and characterize their pre-travel precautions, travel activities, burden of illness, and exposure history. METHODS: With the use of a standardized and validated questionnaire, patients attending a transplant clinic were surveyed regarding recent travel and risk behaviors. RESULTS: Of 267 transplant recipients who participated, 95 (36%) indicated that they had recently traveled outside Canada and the USA. Their mean age was 49.9 years, 54% were male, and 54% were born outside Canada. Eighty-six percent of travelers were receiving at least two immunosuppressive drugs at the time of their trip. Sixty-six percent of travelers sought pre-travel advice, primarily from their transplant physician. Sixty-three percent traveled to areas where hepatitis A is endemic, but only 5% had received hepatitis A immunization. Fifty percent traveled to dengue- and malaria-endemic areas, but,25% adhered to mosquito prevention measures. Ten percent reported behaviors that exposed them to blood or body fluids, including injections, body piercing, and casual sexual activity. CONCLUSIONS: Solid organ transplant recipients represent a unique group of compromised travelers; however, few were adequately protected against travel-associated enteric, vector-borne and bloodborne pathogens.

Effects of aging on the first and second-order kernels of multifocal electroretinogram.

PURPOSE: To determine the effects of aging on the first and second-order kernels of the multifocal electroretinogram (ERG). METHODS: Multifocal ERGs were recorded from 52 healthy subjects (52 eyes) (0 >or= refractive error >or= -3.0 diopter). The ages of the subjects ranged from 12-76 years with a mean (+/-SD) of 44.0 +/- 20.2 years. The Visual Evoked Response Imaging System was used. The effects of aging on the response densities and on the implicit times of the first positive wave (P1) of the first-order kernel, and of the second and third positive waves (P2 and P3) of the second-order kernel were analyzed for the different age groups. RESULTS: The response densities of the first-order kernel P1 and second-order kernel P2 waves decreased significantly, and the implicit times of the second-order kernel P2, and P3 were significantly prolonged (P <.05) in subjects over 50 years of age. CONCLUSION: The results suggest that the age of the subject should be considered when evaluating retinal function using multifocal ERGs in basic and clinical studies.

Changes in the s-wave of multifocal electroretinograms in eyes with primary open-angle glaucoma.

PURPOSE: To determine whether the s-wave is present in the multifocal electroretinogram (mfERG) and whether it is altered in eyes with primary open-angle glaucoma (POAG). METHODS: A Visual Evoked Response Imaging System was used to record mfERGs from 15 eyes of 15 normal adults, as control eyes, and from 15 eyes of 15 patients with POAG. The stimulus consisted of 37 hexagonal stimulating elements with luminances of 200 cd/m(2) (white), 66.6 cd/m(2) (gray), and 4 cd/m(2) (black). The white or black element was presented at five different base periods (bpds) from 13.3 to 213.3 ms according to a binary m-sequence. In the intervals between the white and black (or white) elements, gray elements were inserted at 75 Hz. The changes in the amplitude and implicit time of the s-wave of the all-trace waveform of the first-order kernel of the mfERG were compared with the mean deviation (MD) of retinal sensitivity in the whole visual field measured with a Humphrey Field Analyzer. RESULTS: The s-wave was present as a positive wavelet on the descending limb of the first-order kernel response of the mfERGs of all eyes with POAG. The s-wave amplitude increased with prolongation of the bpd, as occurs in normal eyes. The mean amplitudes of the s-waves at bpds of 53.3 and 106.7 ms were significantly smaller in the eyes with POAG than in the control eyes. The correlation between the s-wave amplitude and the severity of disturbance in the entire visual field indicated by the MD was not significant in eyes with POAG. CONCLUSIONS: The characteristics of the s-wave in glaucomatous eyes were the same as those in the control eyes, but the amplitude of the s-waves in POAG eyes was significantly lower than that in the control eyes. This suggests that ganglion cells may be involved in the development of the s-wave. When comparing the s-wave with static perimetry, more local responses of the s-wave and more local retinal sensitivity in the static perimetry will be appropriate.

Cost-effectiveness of screening for anal precancers in HIV-positive men.

OBJECTIVE: To assess the cost-effectiveness of high-resolution anoscopy (HRA), anal cytology, and anal human papillomavirus (HPV) detection in screening for histologic high-grade anal intraepithelial neoplasia (AIN 2/3) in HIV-positive MSM. DESIGN: Participants were 401 HIV-positive MSM who were screened for anal cancer in a tertiary care HIV clinic. METHODS: A decision analytical model was used to determine the cost-effectiveness of three anal cancer screening strategies: the direct use of HRA; HRA only if anal cytology was abnormal; and HRA only if oncogenic HPV was present. The model included the use of different thresholds for abnormal cytology and also combined cytology and HPV testing. The outcome was the number of AIN 2/3 cases detected. Costs were estimated from institutional data and sensitivity/specificity of cytology and HPV tests were obtained from the screening study. RESULTS: The costs ($ US) per procedure for HRA, cytology, and HPV testing were $193, $90, and $95, respectively. The direct use of HRA was the most cost-effective strategy. It detected 98 individuals with AIN 2/3 and had a cost-effectiveness of $809 per AIN 2/3 case detected. Using probabilistic sensitivity analysis, three other strategies had similar costs per case detected and might be as cost-effective as HRA. CONCLUSION: In HIV-infected MSM, the direct use of HRA is the most cost-effective strategy for detecting AIN 2/3. The higher cost per use for HRA was offset by the high sensitivity and low specificity of HPV and cytology testing.

The role of cytology (Pap tests) and human papillomavirus testing in anal cancer screening.

OBJECTIVE: To assess anal oncogenic human papillomavirus (HPV) and anal cytology as screening tests for detecting high-grade anal intraepithelial neoplasia (AIN 2+), as this is an immediate anal cancer precursor. DESIGN: Cross-sectional study of 401 HIV-positive men who have sex with men (MSM). The endpoint was histologically confirmed AIN 2+ obtained by high-resolution anoscopy. Cytology and biopsy specimens were assigned random numbers and independently assessed by two pathologists. METHODS: We did concomitant anal cytology, anal HPV testing and HRA with directed biopsies without knowing the results of each intervention. The main outcome measures were the sensitivity, specificity, negative predictive value and positive predictive value of anal cytology and oncogenic HPV for the detection of AIN 2+. RESULTS: Cytology was abnormal in 67% of patients: high-grade squamous intraepithelial lesion, 12%; low-grade squamous intraepithelial lesion, 43% and atypical squamous cells of undetermined significance, 12%. Biopsies were abnormal in 68% of patients: AIN 2+, 25% and AIN 1, 43%. HPV was detected in 93% with multiple HPV types in 92% and oncogenic HPV types in 88%. Test performance characteristics for the detection of AIN 2+ using any abnormality on anal cytology were: sensitivity 84%, specificity 39%, negative predictive value 88% and positive predictive value 31%; using oncogenic HPV: sensitivity 100%, specificity 16%, negative predictive value 100% and positive predictive value 28%. CONCLUSION: Anal cytology and HPV detection have high sensitivity but low specificity for detecting AIN 2+. HIV-positive men who have sex with men have a high prevalence of AIN 2+ and require high-resolution anoscopy for optimal detection of high-grade anal dysplasia.

Screening for HIV-associated anal cancer: correlation of HPV genotypes, p16, and E6 transcripts with anal pathology.

BACKGROUND: HIV-positive men with a history of anal-receptive intercourse are at risk for anal cancer. We determined whether human papilloma virus (HPV) biomarkers were correlated with anal pathology in these men. METHODS: HPV genotype was determined by PCR/line blot assay. Real-time PCR assays were done for viral load, E6 transcripts for HPV genotypes 16, 18, and 31, and p16 transcripts. RESULTS: The most common oncogenic HPV types were HPV 16 (38%), 18 (19%), 45 (22%), and 52 (19%). HPV types 16, 18, 31, 52, 59, and 68 were associated with high-grade histology. The number of HPV genotypes per anal swab was higher for anal intraepithelial neoplasia (AIN) 2/3 than for normal or AIN 1 histology [median, 5 types (interquartile range) (IQR), 3-7 versus 3.5 (IQR), 2-6; P = 0.0005]. HPV 16 viral load was also associated with AIN 2/3 histology. There was no difference in p16 or E6 transcripts between histologic grades. In the multivariable logistic regression model, HPV genotypes 16 [odds ratio, 2.58; 95% confidence interval (95% CI), 1.31-5.08; P = 0.006] and 31 (odds ratio, 4.74; 95% CI, 2.00-11.22; P = 0.0004), baseline CD4 count < 400 cells/mm(3) (odds ratio, 2.96; 95% CI, 1.46-5.99; P = 0.0025), and Acquired Immunodeficiency Syndrome (AIDS)-defining illness (odds ratio, 2.42; 95% CI, 1.22-4.82; P = 0.01) were associated with high-grade histology after adjusting for age. CONCLUSIONS: The presence of high-grade anal pathology (AIN 2/3) in HIV-positive men was associated with multiple HPV genotypes, HPV genotypes 16 and 31, and HPV 16 viral load.

Interobserver agreement in the interpretation of anal intraepithelial neoplasia.

BACKGROUND: Anal carcinoma incidence is increasing, and is highest among men with human immunodeficiency virus (HIV) infection who have sex with men. Anal carcinoma and anal intraepithelial neoplasia (AIN) are ascertained on tissue histology, but requires invasive procedures. Screening for AIN using anal cytology was suggested. The authors evaluated agreement on cytologic and biopsy specimens from HIV-positive men undergoing anal carcinoma screening. METHODS: One hundred twenty-nine HIV-positive men with a history of anal-receptive intercourse underwent anal cytology, anoscopy, and biopsy. Four pathologists independently assessed cytology and biopsy specimens and reached consensus for discordant cases. RESULTS: Each pathologist evaluated 120 cytology and 155 biopsy specimens. The weighted kappa value for overall agreement was 0.54 (95% confidence interval [CI], 0.49-0.59) for cytology specimens and 0.59 (95%CI, 0.55-0.63) for biopsy specimens. The median kappa values for pairwise agreement among pathologists and for agreement with consensus were, respectively, 0.69 and 0.77 for cytology and 0.66 and 0.75 for biopsy. At least 3 pathologists were in agreement for 92 (76.7%) cytology and 134 (86.5%) biopsy specimens. Reliability for the Bethesda classification system was at least moderate, except for the cytologic category of atypical squamous cells of undetermined significance (kappa = 0.12). Fourteen of 29 (48.3%) cytology specimens and 36 of 47 (76.6%) biopsy specimens with consensus interpretation of high-grade squamous intraepithelial lesions (HSIL) were interpreted originally as HSIL by > or = 3 pathologists. The kappa value for agreement with consensus distinguishing HSIL from non-HSIL ranged from 0.55 to 0.88 for cytology specimens and from 0.76 to 0.94 for biopsy specimens. CONCLUSIONS: Agreement for cytologic and biopsy interpretations was generally at least moderate. Nevertheless, these results supported the need for disease indicators with greater reliability.