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Introduction Early systemic and central nervous system viral replication and inflammation may impact brain integrity in people with HIV (PWH), leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART. Methods HIV-infected MSM and transgender women (average age: 27 and education: 13 years) enrolled within 100 days from estimated date of detectable infection [EDDI]. A cognitive performance (NP) protocol was administered at enrollment (before ART initiation) and every 24 weeks until week 192. An overall index of cognitive performance (NPZ) was created using local normative data. Blood (n=87) and cerebrospinal fluid (CSF; n=29) biomarkers of inflammation and neuronal injury were examined before ART initiation. Regression analyses assessed relationships between time since EDDI, pre-ART biomarkers, and NPZ. Results Adjusting for multiple comparisons, shorter time since EDDI was associated with higher pre-ART VL and multiple biomarkers in plasma and CSF. NPZ scores were within the normative range at baseline (NPZ=.52) and at each follow-up visit, with a modest increase through week 192. Plasma or CSF biomarkers were not correlated with NP scores at baseline or after ART. Conclusions Biomarkers of CNS inflammation, immune activation and neuronal injury peak early and then decline during acute HIV infection, confirming and extending results of other studies. Neither plasma nor CSF biomarkers during acute infection corresponded to NP scores before or after sustained ART in this cohort with few psychosocial risk factors for cognitive impairment.

Background Introduction: The impact of Covid-19 pandemic on the health services across the world is well documented. Aim We wished to determine the impact of the pandemic on the provision of endoscopy services and its effect on oesophageal and gastric cancers in our health board. Methods A retrospective analysis of data collected from the major cancer network pathway (MCN) database for patients diagnosed with Oesophageal and Gastric cancers for the NHS Ayrshire and Arran Health board in Scotland was performed. Data was collected for the year 2019 (pre-pandemic) and the year 2020 (pandemic) between 1st of January and 31st December for the respective years. Number of UGI endoscopy procedures performed, mode of presentation, stage at presentation and treatment intent were primary outcome measures. Data was analysed using stata17 software Results Data was recorded in 99 and 91 patients with OG cancers for the year 2019 and 2020 respectively. A total of 4176 and 1763 procedures were carried out during the 2 periods respectively. An increase in emergency presentations from 22 to 46% (p Conclusions The COVID-19 pandemic has had a significant impact on the endoscopy services and management of oesophageal and gastric cancers with an increase in non-Covid harm due to the pandemic.

The trial of a turbine powered Motorized Reaming Shoe (MRS) was conducted on two fields offshore Abu Dhabi involving the running of 9-5/8″ casing to planned depths in long intermediate sections. The trials involved running casing in the longest12-1/4″ sections to date on each field. This paper will elaborate on detailed parameters, Motorized Reaming Shoe features and operating practices recorded while reaming through multiple restrictions with a cumulative length of more than 200 ft, across various formations, successfully running casing to the planned depth. It will also elaborate on casing cementing and shoe-track drilling operations where MRS were deployed. Referring to the average NPT duration of similar incidents, this initiative has saved 6 to 7 days of operation (eliminating requirement to pull the casing, perform a wiper trip, and re-run back the casing). This is estimated at an average of approximately 1M$ cost savings per NPT event. The failure to run casing to section TD with the MRS in one of the trial jobs is also analyzed including detailed operational learnings and design changes that could positively impact running long casing strings in complex wells. This paper details the technical features and potential benefits of Turbine Powered Reaming Systems, how the trials were conducted and their impact on de-risking casing deployments, with specific reference to application in long intermediate casing sections offshore Abu Dhabi.

Blood flow autoregulation in cerebral white matter was measured before and after acute nicardipine-induced changes in mean arterial pressure of 10-21% in 21 treatment naïve HIV-positive adults and 32 controls. The autoregulatory index (-% cerebral blood flow change/% mean arterial pressure change) was not different at baseline ( P = 0.71) or after 1 year of treatment ( n = 11, P = 0.17). We found no autoregulatory defect to explain the increased stroke risk or the development of cerebral white damage in people with HIV.

Fire is an integral component of ecosystems globally and a tool that humans have harnessed for millennia. Altered fire regimes are a fundamental cause and consequence of global change, impacting people and the biophysical systems on which they depend. As part of the newly emerging Anthropocene, marked by human-caused climate change and radical changes to ecosystems, fire danger is increasing, and fires are having increasingly devastating impacts on human health, infrastructure, and ecosystem services. Increasing fire danger is a vexing problem that requires deep transdisciplinary, trans-sector, and inclusive partnerships to address. Here, we outline barriers and opportunities in the next generation of fire science and provide guidance for investment in future research. We synthesize insights needed to better address the long-standing challenges of innovation across disciplines to (i) promote coordinated research efforts; (ii) embrace different ways of knowing and knowledge generation; (iii) promote exploration of fundamental science; (iv) capitalize on the “firehose” of data for societal benefit; and (v) integrate human and natural systems into models across multiple scales. Fire science is thus at a critical transitional moment. We need to shift from observation and modeled representations of varying components of climate, people, vegetation, and fire to more integrative and predictive approaches that support pathways toward mitigating and adapting to our increasingly flammable world, including the utilization of fire for human safety and benefit. Only through overcoming institutional silos and accessing knowledge across diverse communities can we effectively undertake research that improves outcomes in our more fiery future.

There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

Esophagogastroduodenoscopy can be uncomfortable and distressing with many patients opting for conscious sedation over topical local anesthetic spray. Transnasal endoscopy is an alternative and we sought to assess how easily it could be introduced to a district general hospital and how acceptable patients found it. Selected patients requiring diagnostic endoscopy were offered transnasal endoscopy with topical nasal anesthetic by clinicians new to transnasal endoscopy but competent at esophagogastroduodenoscopy. Postal feedback questionnaires were used to assess comfort, distress, recollection of periprocedural consultation, and overall experience (visual analog scale 1-10). A total of 213 transnasal endoscopy procedures were undertaken with 207 completed successfully (97.2%). Two patients (0.9%) had self-limiting epistaxis and no patient required admission. One hundred (47%) questionnaires were returned including 98 from those with completed transnasal endoscopy. Thirty-three (33%) had previous esophagogastroduodenoscopy and 28 (85%) reported a preference for transnasal endoscopy. Fifty-eight patients (59%) found transnasal endoscopy comfortable (visual analog scale6) with 17 reporting discomfort (visual analog scale5). Seventeen patients found the procedure distressing (visual analog scale6) but 70 (73%) did not (visual analog scale5). Eighty-four patients (85.7%) had clear recollection of their procedure (visual analog scale6) and overall satisfaction was reported as good (visual analog scale6) by 94.7%. Transnasal endoscopy can be adopted by clinicians competent with conventional esophagogastroduodenoscopy with expectation of high procedure completion rate and low complication rate. Our patients reported high levels of satisfaction with few reporting distress. Perhaps as a consequence, most patients had a clear recollection of their procedure.

OBJECTIVES The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI). DESIGN Single-arm, open-label pilot study of participants with AHI initiating ritonavir-boosted darunavir 800 mg once daily and etravirine 400 mg once daily or 200 mg twice daily within 30 days of AHI diagnosis. METHODS Efficacy was defined as HIV RNA less than 200 copies/ml by week 24. Optional sub-studies included pharmacokinetics analysis from genital fluids (weeks 0-4, 12, 48), cerebrospinal fluid (CSF) (weeks 2-4, 24 and 48) and endoscopic biopsies (weeks 4-12 and 36-48). Neuropsychological performance was assessed at weeks 0, 24 and 48. RESULTS Fifteen AHI participants were enrolled. Twelve (80%) participants achieved HIV RNA less than 200 copies/ml by week 24. Among 12 participants retained through week 48, nine (75%) remained suppressed to less than 50 copies/ml. The median time from ART initiation to suppression less than 200 and less than 50 copies/ml was 59 and 86 days, respectively. The penetration ratios for etravirine and darunavir in gut associated lymphoid tissue were 19.2 and 3.05, respectively. Most AHI participants achieving viral suppression experienced neurocognitive improvement. Of the three participants without overall improvement in neurocognitive functioning as measured by impairment ratings (more than two tests below 1 SD), two had virologic failure. CONCLUSION NRTI-sparing ART started during AHI resulted in rapid viral suppression similar to NRTI-based regimens. More novel and compact two-drug treatments for AHI should be considered. Early institution of ART during AHI appears to improve overall neurocognitive function and may reduce the risk of subsequent neurocognitive impairment. CLINICALTRIALS.GOV:: NCT00855413.

HIV-1 compartmentalization in the central nervous system (CNS) and its contribution to neurological disease have been well documented. Previous studies were conducted among people infected with subtypes B or C where CNS compartmentalization has been observed when comparing viral sequences in the blood to virus in cerebrospinal fluid (CSF). However, little is known about CNS compartmentalization in other HIV-1 subtypes. Using a deep sequencing approach with Primer ID, we conducted a cross-sectional study among Nigerian and Malawian HIV-1 cohorts with or without fungal Cryptococcus infection diagnosed as cryptococcal meningitis (CM) to determine the extent of CSF/CNS compartmentalization with CM. Paired plasma and CSF samples from 45 participants were also analyzed for cytokine/chemokine levels. Viral populations comparing virus in the blood and the CSF ranged from compartmentalized to equilibrated, including minor or partial compartmentalization or clonal amplification of a single viral sequence. The frequency of compartmentalized viral populations in the blood and CSF was similar between the CM− and CM+ participants. We confirmed the potential to see compartmentalization with subtype C infection and have also documented CNS compartmentalization of an HIV-1 subtype G infection. Cytokine profiles indicated a proinflammatory environment, especially within the CSF/CNS. However, sCD163 was suppressed in the CSF in the presence of CM, perhaps due to elevated levels of IL-4, which were also a feature of the cytokine profile, showing a distinct cytokine profile with CM.

Background We assessed the utility of the International HIV Dementia Scale (IHDS) in detecting HIV-associated neurocognitive disorder (HAND) in Uganda in antiretroviral (ART)-naive and ART-experienced adults. Setting A longitudinal observational cohort study in Rakai, Uganda. Methods Three hundred ninety-nine HIV+ ART-naive adults underwent neurological, functional status, and neuropsychological assessments including the IHDS. Three hundred twelve participants who initiated ART were re-evaluated after 2 years. HAND stages [asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia (HAD)] were determined based on Frascati criteria using local normative data. Sensitivity, specificity, and area under the ROC curve were determined for various IHDS thresholds (≤9, ≤ 9.5, and ≤10). Results At baseline, the participants' mean age was 35 years (SD ± 8), 53% were men, and 84% had less than a high school education. At baseline, sensitivity for detecting any HAND stage, symptomatic HAND [mild neurocognitive disorder, HAD], and HAD alone were maximized at IHDS ≤10 (81%, 83%, 92%, respectively). Among 312 individuals who returned for the 2-year follow-up and had initiated ART, a score of ≤10 provided a lower or equal sensitivity for detecting different stages of HAND (all HAND: 70%; symptomatic HAND: 75%; HAD: 94%). The area under the ROC curve was higher for ART-experienced versus ART-naive individuals. Conclusions The IHDS is a potentially useful screening tool for neurocognitive impairment in rural Uganda for both ART-naive and ART-experienced adults. A cutoff ≤10 demonstrates higher sensitivity for more severe HAND stages compared with less severe HAND. Future studies should focus on potential modifications to the IHDS to improve its specificity.

Decreased cognitive function is related to undesirable psychological outcomes such as greater emotional distress and lower quality of life, particularly among women living with HIV who experience cognitive impairment (WLWH-CI). Yet, few studies have examined the psychosocial resources that may attenuate these negative emotional outcomes. The current study sought to identify the interrelated contributions of social relationships and psychological resources in 399 WLWH-CI by applying Socio-Emotional Adaptation (SEA) theory using data from the Women's Interagency HIV Study (WIHS). Cognitive impairment (CI) was defined as impairment on two or more cognitive domains. Logistic regression models were used to estimate the odds of experiencing specific emotions due to a combination of four psychosocial resources. Emotions (i.e., depression, apathy, fear, anger, and acceptance) were related to a combination of binary (positive/negative) psychosocial resources including relationship with an informal support partner, relationship with a formal caregiver, coping, and perceived control. Understanding the conditions that may influence emotions in WLWH-CI is important for identifying and appropriately addressing the needs of this population. As CI increases, these individuals experience increasing challenges with articulating their care needs and having their needs met. As such, it becomes increasingly important to identify possible triggers for emotional responses to best address these underlying challenges.

Digital offshore operations and analysis rely on the deployment of downhole completion technologies that can produce significant quantities of data. Historically, downhole monitoring technologies, such as fiber optics and permanent downhole gauges, have been a good source of wellbore data for modeling and analysis. Permanent downhole monitoring technologies have benefitted from the advancement of high temperature electronics, reducing overall power consumption, and directly affecting sensor and electronics reliability and longevity. Through the utilization of telemetry schemes for addressability, permanent downhole monitoring technologies have also helped to develop electro-hydraulic and all-electric downhole flow control technologies, by enabling increased wellbore compartmentalization and fast control of multiple wellbore intervals. Advanced reservoir control systems have the ability to integrate to smart and data driven systems. They can be subdivided into extrinsic and intrinsic systems. Intrinsic systems benefit from having integrated monitoring technologies that can be addressed through telemetry schemes, which are also used to control multiple wellbore intervals. Examples of intrinsic systems include intrinsic electro-hydraulic systems and all-electric systems. To date, plenty of testing has been done with these types of intrinsic systems, but this paper highlights the evaluation of an intrinsic electro-hydraulic system. Ultimately, the authors believe that a stepwise approach through the implementation of hybrid-electric digital systems is key to the overall acceptance of all-electric systems. The success and reliability of electro-hydraulic systems will play a significant role in mass acceptance of all-electric systems in the oilfield. Electro-hydraulic systems are a good segway into all electric systems and give operators the chance to utilize some of the existing infrastructure while benefiting from some of the optimizations brought on by the Digital Oilfield.

OBJECTIVES HIV-associated neurocognitive disorders (HAND) remain prevalent in people living with HIV (PLWH) despite widespread use of combined antiretroviral therapy (ART). Vascular disease contributes to the pathogenesis of HAND, but traditional vascular risk factors do not fully explain the relation between vascular disease and HAND. A more direct measure of vascular dysfunction is needed. This cross-sectional study tested whether the cardio-ankle vascular index (CAVI), a novel method to assess arterial stiffness, is associated with HAND among PLWH. METHODS Participants included 75 non-diabetic adults with well-controlled HIV from an outpatient HIV clinic. We assessed the relation between CAVI and neurocognitive impairment (NCI). The latter was primarily characterized by the Frascati criteria and secondarily (post hoc) using the Global Deficit Score (GDS). Logistic regression models tested whether high CAVI (≥ 8) was independently associated with NCI when controlling for potential confounders. RESULTS Participants (Mage = 45.6 ± 8.3 years; 30.1% male) had few traditional cardiovascular disease (CVD) risk factors (hypertension, n = 7; dyslipidaemia, n = 34; body mass index ≥ 25 kg/m2 , n = 12; smoking history, n = 13; 2.2% mean 10-year risk of CVD or stroke). Twelve (16%) participants had high CAVI, which was independently associated with meeting Frascati criteria for NCI [n = 39, odds ratio (OR) = 7.6, p = 0.04], accounting for age, education, gender, income, CD4 nadir, recent CD4 and traditional CVD risk factors. High CAVI was also associated with NCI as reflected by higher GDS (OR = 17.4, p = 0.02). CONCLUSIONS Cardio-ankle vascular index is a promising measure of vascular dysfunction that may be independently associated with NCI in relatively healthy PLWH. Larger studies should test the utility of CAVI in predicting NCI/decline in PLWH.

The AIDS Clinical Trials Group (ACTG) study A5303 investigated the associations between neuropsychological performance (NP) and inflammatory biomarkers in HIV-infected participants. Fifteen NP tests were administered at baseline and week 48 to 233 ART naïve participants randomized to maraviroc- or tenofovir-containing ART. Neurocognition correlated modestly with markers of lymphocyte activation and inflammation pre-ART (percent CD38+/HLA-DR+(CD4+) (r = − 0.22, p = 0.02) and percent CD38+/HLA-DR+(CD8+) (r = − 0.25, p = 0.02)), and with some monocyte subsets during ART (r = 0.25, p = 0.02). Higher interleukin-6 and percent CD38+/HLA-DR+(CD8+) were independently associated with worse severity of HIV-associated neurocognitive disorders (HAND) (p = 0.04 and 0.01, respectively). More studies to identify HAND biomarkers are needed.

Background Distal sensory peripheral neuropathy (DSPN) is a complication of human immunodeficiency virus (HIV). We estimate DSPN prevalence in 7 resource-limited settings (RLSs) for combination antiretroviral therapy (cART)–naive people living with HIV (PLWH) compared with matched participants not living with HIV and in PLWH virally suppressed on 1 of 3 cART regimens. Methods PLWH with a CD4+ count Associations between covariates with DSPN at entry were assessed using the χ2 test, and virally suppressed PLWH were assessed using generalized estimating equations. Results Before initiating cART, 21.3% of PLWH had DSPN compared with 8.5% of people not living with HIV (n = 2400; χ2(df = 1) = 96.5; P < .00001). PLWH with DSPN were more likely to report inability to work [χ2(df = 1) = 10.6; P = .001] and depression [χ2(df = 1) = 8.9; P = .003] than PLWH without DSPN. Overall prevalence of DSPN among those virally suppressed on cART decreased: 20.3%, week 48; 15.3%, week 144; and 10.3%, week 192. Incident DSPN was seen in 127 PLWH. Longitudinally, DSPN was more likely in older individuals (P < .001) and PLWH with less education (P = .03). There was no significant association between cART regimen and DSPN. Conclusions Although the prevalence of DSPN decreased following cART initiation in PLWH, further research could identify strategies to prevent or ameliorate residual DSPN after initiating cART in RLSs.

Objective To examine associations between plasma cystatin C and neurocognitive impairment (NCI) and its performance as a diagnostic marker before and during initial antiretroviral therapy (ART). Methods Multivariable logistic regression and generalized estimating equations examined associations with NCI, determined by neuropsychological measurements, in participants of a 48-week randomized clinical trial of initial ART. Receiver operator characteristic curves examined diagnostic models of NCI. Results Cystatin C was associated with NCI before ART [odds ratio (OR) 3.4 (95% CI: 1.2 to 9.4) for each 2-fold increase in baseline levels] and during 48 weeks of ART, in models that excluded baseline measurements [OR 3.0 (1.2 to 7.8) for each 2-fold increase in time-updated levels]. The strength of association increased with more severe impairment using HIV-associated neurocognitive disorder criteria [OR 2.2 (0.8 to 6.0) with asymptomatic NCI and OR 4.0 (1.5 to 11.0) with mild neurocognitive disorder or HIV-associated dementia vs. no impairment, for each 2-fold increase in time-updated levels] or by global development score [OR 2.6 (1.1 to 6.3) with mild impairment and OR 4.6 (1.1 to 18.9) with moderate or severe impairment vs. no impairment]. Cystatin C performed poorly as a diagnostic marker for NCI, however, with an area under the receiver operator characteristic curve of 0.58 at baseline and 0.54 at week 48. Conclusions Higher plasma cystatin C levels were significantly associated with NCI, but these levels did not seem to be useful as a diagnostic marker for this condition.

Headache is common, but its prevalence and impact in sub-Saharan Africa and especially in HIV+ individuals is relatively unknown. We sought to determine the prevalence and functional impact of headache among HIV-infected (HIV+) adults in a cross-sectional observational cohort study in rural Rakai District, Uganda. Participants completed a sociodemographic survey, depression screen, functional status assessments, and answered the headache screening question, "Do you have headaches?" Participants responding affirmatively were assessed with the ID Migraine tool for diagnosis of migraine and Headache Impact Test-6 to determine functional impact of headache. Characteristics of participants with and without headaches and with and without functional impairment were compared using t tests for continuous variables, chi-square tests for categorical variables, and multivariate logistic regression. Of 333 participants, 51% were males, mean age was 37 (SD 9) years, 94% were on antiretroviral therapy (ART) and mean CD4 count was 403 (SD 198) cells/μL. Headache prevalence was 28%. Among those reporting headache, 19% met criteria for migraine, 55% reported functional impairment, and 37% reported substantial or severe impact of headache. In multivariate analyses, female sex (odds ratio (OR) 2.58) and depression (OR 2.49) were associated with increased odds and ART (OR 0.33) with decreased odds of headache. Participants with substantial/severe functional impact were more likely to meet criteria for depression (32% vs 9%). In conclusion, headache prevalence in HIV+ rural Ugandans was lower than global averages but still affected more than one quarter of participants and was associated with significant functional impairment.

Objective: Efavirenz (EFV) use is associated with neuropsychiatric side effects, which may include poor neurocognitive performance. We evaluated single nucleotide polymorphisms in genes that contribute to EFV pharmacokinetics and examined them in association with EFV concentrations in plasma and hair, as well as neurocognitive performance. Design: Cross-sectional study in which adults with HIV receiving 600-mg EFV for at least 2 months were recruited and paired hair and dried blood spots (DBS) samples collected. Methods: Participants (N = 93, 70.3% female) were genotyped for seven single nucleotide polymorphisms in CYP2B6, NRII3 and ABCB1 using DBS. EFV was quantified in DBS and hair using validated liquid-chromatography–tandem-mass-spectrometry methods, with plasma EFV concentrations derived from DBS levels. Participants were also administered a neurocognitive battery of 10 tests (seven domains) that assessed total neurocognitive functioning. Results: Strong correlation (r = 0.66, P T, (P C (P = 0.001) were each associated with hair EFV concentrations. Similarly, 516G>T (P C (P = 0.009) were significantly associated with plasma EFV concentration. No other genetic associations were observed. Contrary to other studies, total neurocognitive performance was significantly associated with plasma EFV concentrations (r = 0.23, P = 0.043) and 983T>C genotype (r = 0.38, P

There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

Biological and ecological important areas and species are in increasing focus now. Earlier protected areas have mostly excluded productive forest areas in Norway. The added focus on these areas combined with an increased interest in biodiversity has led to the production of this study. It was therefore examined to see if it was possible to categorize these degrees of naturalness and to see if it was possible to remotely sense these areas. The remote sensing technique if successful will decrease time and costs used identifying these areas in the field. In this study Airborne Laser Scanning data was used in conjunction with data collected in the field to see if it was possible to determine old natural forests and to see if it was possible to distinguish between the naturalness categories using ALS. It was decided to use Random Forest decision tree model to predict the factors from the ALS that were the most important in the predication of naturalness. Height variables were the variables that were deemed the most decisive according to the Random Forest Analysis. The aim of this thesis is to evaluate methods to map ONFs using ALS. More specifically the objective was to include methods to maps the ONFs gradient of definitions to six categories. Untouched (virgin), ancient, semi-natural, old-selective, old managed, and managed. M-SF

Background Individuals with previous syphilis may experience cognitive impairment. The goal of this study was to determine if those at high risk for laboratory-defined neurosyphilis are cognitively impaired, and whether treatment based on cerebrospinal fluid (CSF) findings results in better outcomes. Methods Participants had a new syphilis diagnosis, serum RPR titer ≥ 1:32 or peripheral blood CD4+ T cells ≤ 350/ul (in persons living with HIV) and did not endorse neurological symptoms. They underwent computerized cognitive assessment with the CogState. Thirty-two were randomized to either undergo lumbar puncture (LP) or to not undergo LP and 14 underwent LP; 64 were not randomized and 48 opted to undergo LP. Results Demographics, cognitive complaints and cognitive impairment did not differ between randomized and nonrandomized participants. Two-thirds were cognitively impaired, and impairment was not more common in those with cognitive complaints. The adjusted odds of increased severity of impairment were 3.8 times greater in those with CSF pleocytosis compared to those without. Time to cognitive normalization, improvement or decline did not differ between those who did not undergo LP and those who underwent LP and whose treatment was based on CSF analysis. Taking into account pre-treatment cognitive impairment, the risk of cognitive decline was lower in those with CSF pleocytosis treated for neurosyphilis compared to those without CSF pleocytosis not treated for neurosyphilis, (HR 0.24 (95% CI 0.07–0.88], p = 0.03). Conclusion In individuals at high risk for laboratory-defined neurosyphilis, cognitive complaints are not a good indicator of cognitive impairment. Severity of cognitive impairment was greater in those with CSF pleocytosis. Identification and treatment of those with neurosyphilis may mitigate subsequent cognitive decline.

BackgroundCardiovascular disease (CVD) and associated comorbidities increase the risk of cognitive impairment in persons living with human immunodeficiency virus (PLWH). Given the potential composite effect of multiple cardiovascular risk factors on cognition, we examined the ability of the Atherosclerotic Cardiovascular Disease (ASCVD) risk score and the Framingham Heart Study Global CVD risk score (FRS) to predict future cognitive function in older PLWH.MethodsWe constructed linear regression models evaluating the association between baseline 10-year cardiovascular risk scores and cognitive function (measured by a summary z-score, the NPZ-4) at a year 4 follow-up visit.ResultsAmong 988 participants (mean age, 52 years; 20% women), mean 10-year ASCVD risk score at entry into the cohort was 6.8% (standard deviation [SD], 7.1%) and FRS was 13.1% (SD, 10.7%). In models adjusted only for cognitive function at entry, the ASCVD risk score significantly predicted year 4 NPZ-4 in the entire cohort and after stratification by sex (for every 1% higher ASCVD risk, year 4 NPZ-4 was lower by 0.84 [SD, 0.28] overall, P = .003; lower by 2.17 [SD, 0.67] in women, P = .001; lower by 0.78 [SD, 0.32] in men, P = .016). A similar relationship was observed between FRS and year 4 NPZ-4. In multivariable models, higher 10-year ASCVD risk and FRS predicted lower NPZ-4 in women.ConclusionsBaseline 10-year ASCVD risk and FRS predicted future cognitive function in older PLWH with well-controlled infection. Cardiovascular risk scores may help to identify PLWH, especially women, who are at risk for worse cognition over time.

We investigated the prevalence and risk factors for frailty among people with HIV (PWH) in rural Uganda (n = 55, 47% male, mean age 44 years). Frailty was defined according to the Fried criteria with self-reported physical activity level replacing the Minnesota Leisure Time Activity Questionnaire. Alternate classifications for physical activity utilized were the sub-Saharan Africa Activity Questionnaire and the International Physical Activity Questionnaire. Eleven participants (19%) were frail. Frail participants were older (p

Objectives Few studies have assessed cognitive impairment among healthy people living with HIV (PLWH) who are stable on antiretroviral treatment (ART) in sub-Saharan Africa. Methods We conducted a cross-sectional study among a random sample of stable adult PLWH from rural Tanzania on ART for more than 1 year and without immunological failure or pre-existing neurological disease. We evaluated the prevalence and risk factors for neurocognitive impairment (NCI), assessed through neuropsychological tests, functional and depression questionnaires and defined as a mean Z-score ≤ -1 in two or more cognitive domains. Results Among 243 participants [median age = 44.3 years (interquartile range: 36-52] and 71% female] we found a rate of NCI of 19.3% (95% confidence interval: 14.8-24.8%). Memory and psychomotor domains demonstrated the highest impairment. Independent predictors of NCI were age and self-reported alcohol use. Other classical risk factors were not associated with HIV-associated NCI. Conclusion Despite effective ART roll-out, NCI remained a prevalent condition in this healthy rural Tanzanian population of PLWH on ART. Age and alcohol use were key risk factors.

BACKGROUND HIV-associated neurocognitive disorders remain prevalent despite effective antiretroviral therapy (ART), but there are limited longitudinal data on people living with HIV (PLWH) in sub-Saharan Africa. We examined neuropsychological (NP) performance in PLWH in a longitudinal study in Uganda. METHODS Participants enrolled through the Rakai Community Cohort Study (400 ART-naive PLWH and 400 matched HIV-negative persons) were administered NP assessments. In 2017, PLWH who had initiated ART underwent a 2-year follow-up assessment. Demographically adjusted Z-scores for each NP test were established using data from the HIV- controls. Multivariable linear and logistic regressions were conducted to examine group differences in NP performance. Mixed-effects regressions were conducted to examine ART-related changes in NP outcomes. RESULTS Of 333 PLWH who returned for their 2-year follow-up visit, 312 (94%) had initiated ART. Those on ART had a mean age of 35.6 years (SD ± 8.5 years) and mean education of 5.4 years (SD ± 3.3 years); 49% were women. ART-associated NP improvements occurred in verbal learning and memory (P's < 0.05), motor (P's < 0.01), and some measures of processing speed (P = 0.002), whereas there were declines in attention/working memory (P's < 0.001) and semantic fluency (P < 0.001). Pre-ART CD4 count and efavirenz use were associated with a more impaired change in NP performance. CONCLUSIONS PLWH in this resource-limited setting showed improved neurocognitive performance on most NP tests after ART initiation. However, the declines in attention/working memory and fluency performance, as well as relationship to efavirenz, warrant further study.

Background Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs. Methods We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points. Results For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity. Conclusions Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.

ObjectiveTo identify the neural markers of attention dysfunction in patients with HIV-associated neurocognitive disorder (HAND).MethodsSixty participants, including 40 HIV-infected adults (half with HAND) and 20 demographically matched controls performed a visual selective attention task while undergoing high-density magnetoencephalography. Neuronal activity related to selective attention processing was quantified and compared across the 3 groups, and correlated with neuropsychological measures of attention and executive function. Spontaneous neural activity was also extracted from these attention-related cortical areas and examined with respect to HAND status.ResultsHIV-infected participants with and without HAND exhibited behavioral selective attention deficits on the magnetoencephalography task, as indicated by an increased flanker effect. Neuronal measures of flanker interference activity in the alpha and theta range revealed differential dynamics in attention-related brain areas across the 3 groups, especially in those with HAND. In addition, theta range flanker interference activity in the left inferior frontal and dorsolateral prefrontal cortex was associated with executive function and attention composite scores, respectively. Progressively stronger spontaneous alpha and theta activity was also found in unimpaired HIV-infected and HAND participants relative to controls across brain regions implicated in different components of attention processing.ConclusionsBehavioral and neuronal metrics of selective attention performance distinguish participants with HAND from controls and unimpaired HIV-infected participants. These metrics, along with measures of local spontaneous neural activity, may hold promise as early markers of cognitive decline in participants with HIV infection and be useful prognostic indicators for HAND.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders can persist in many patients despite achieving viral suppression while on antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated using a Cogstate test battery assessing psychomotor function, attention, learning, and working memory in 293 HIV-1-infected, ART-experienced, and virologically suppressed adults. The ASSURE study randomized participants 1:2 to remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Neurocognitive z-scores were computed using demographically adjusted normative data and were classified as “impaired” (defined as either a z-score ≤ − 2 or having 2 or more standardized individual test z-scores ≤ − 1); while higher scores (equaling better performance) were classified as “normal”. By z-scores, 54.7% of participants had impaired neurocognition at baseline and 50.2% at week 48. There were no significant differences (p

BACKGROUND: AIDS Clinical Trial Group 5199 compared neurological and neuropsychological test performance of human immunodeficiency virus type 1 (HIV-1)–infected participants in resource-limited settings treated with 3 World Health Organization–recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes. METHODS: Standardized neurological and neuropsychological examinations were administered every 24 weeks. Generalized estimating equation models assessed the association between TB and neurological/neuropsychological performance. RESULTS: Characteristics of the 860 participants at baseline were as follows: 53% female, 49% African; median age, 34 years; CD4 count, 173 cells/μL; and plasma HIV-1 RNA, 5.0 log copies/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary, and 1 case of central nervous system (CNS) TB. Over the 192 weeks of follow-up, there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB coinfection had significantly poorer performance on grooved pegboard (P < .001) and fingertapping nondominant hand (P < .01). TB was associated with diffuse CNS disease (P < .05). Furthermore, those with TB had 9.27 times (P < .001) higher odds of reporting decreased quality of life, and had 8.02 times (P = .0005) higher odds of loss of productivity. CONCLUSIONS: TB coinfection was associated with poorer neuropsychological functioning, particularly the fine motor skills, and had a substantial impact on functional ability and quality of life. CLINICAL TRIALS REGISTRATION: NCT00096824.

While the arrival of combination antiretroviral therapy significantly decreased the prevalence of HIV-associated dementia, between 35 and 70% of all infected adults continue to develop some form of cognitive impairment. These deficits appears to affect multiple neural subsystems, but the mechanisms and extent of damage are not fully understood. In the current study, we utilized magnetoencephalography (MEG), advanced oscillatory analysis methods, and a paired-pulse somatosensory stimulation paradigm to interrogate pre-attentive inhibitory processing in 43 HIV-infected adults and 28 demographically-matched uninfected controls. MEG responses were imaged using a beamformer, and time series data were extracted from the peak voxel in grand-averaged functional brain images to quantify the dynamics of sensory gating, oscillatory power, spontaneous power, and other neural indices. We found a significantly weakened response to the second stimulation compared to the first across groups, indicating significant sensory gating irrespective of HIV-infection. Interestingly, HIV-infected participants exhibited reduced neural responses in the 20–75 Hz gamma range to each somatosensory stimulation compared to uninfected controls, and exhibited significant alterations in peak gamma frequency in response to the second stimulation. Finally, HIV-infected participants also had significantly stronger spontaneous activity in the gamma range (i.e., 20–75 Hz) during the baseline period before stimulation onset. In conclusion, while HIV-infected participants had the capacity to efficiently gate somatosensory input, their overall oscillatory responses were weaker, spontaneous baseline activity was stronger, and their response to the second stimulation had an altered peak gamma frequency. We propose that this pattern of deficits suggests dysfunction in the somatosensory cortices, which is potentially secondary to accelerated aging., Highlights • Around half of all HIV-infected patients will develop cognitive impairments during their life. • The underlying mechanisms are unknown, but inhibitory deficits are thought to be critical. • We examined oscillatory activity using MEG in 71 HIV-infected and uninfected adults. • Gamma oscillatory dynamics were significantly disturbed in HIV-infected adults.

We assessed the value of screening for cognitive abnormalities in a chronically infected HIV population (N = 388) and investigated the association with clinical correlates. The mean age was 48 years (±11), the majority of the patients were male (89%), the median duration of infection was 6 years [interquartile range (IQR) = 2–12], the median CD count was 600 (IQR = 450–780), and 326 (84%) had a viral load below 200 copies/mL. Screening for cognitive complaints was applied using the three Simioni questions and the international HIV dementia scale (iHDS). Neuropsychological assessment (NPA) included 13 well-validated tests assessing motor speed, concentration, and memory. A total of 69 patients completed the NPA. CD4 (nadir), viral load, combination antiretroviral therapy (cART) duration, and the presence of comorbidities were evaluated for associations with NPA result. A total of 127 (33%) reported cognitive complaints during screening. The sensitivity and specificity of the Simioni questions were 82% and 24%, respectively. Adding the iHDS resulted in a sensitivity of 50% and a specificity of 73%. A CD4 nadir count

ObjectivesHIV rapid antibody tests are widely used in Africa, but dual testing sometimes produces discordant results. It is not clear if discordant rapid HIV tests should always heighten suspicion by frontline health workers that early HIV infection is present. Some studies have reported that discordant rapid tests have value for identifying early HIV infection in high HIV prevalence populations. It is not known if rapid test performance influenced this conclusion, or if this observation will hold true for low HIV prevalence populations. We therefore explored the occurrence of discordant rapid HIV tests in a low-resource community.MethodsA cross-sectional sample of HIV status-unaware adults with recent exposure to unsafe sex was assessed using a validated risk-based tool (University of North Carolina (UNC)-Malawi Risk Screening Score) for acute HIV infection. Participants received rapid testing with Determine HIV 1/2 and Uni-Gold HIV assays, plus plasma HIV-1 antigen testing with the COBAS((R)) Ampliprep/COBAS((R)) Taqman((R)) HIV-1 assay, followed by western blot in those with detected HIV-1 antigen.ResultsOf 408 participants, 1.0% were confirmed to have established HIV infection. The discordance between rapid tests at initial screening was 2.45 and 2.94% when the two assays were used sequentially and simultaneously, respectively. Discordant rapid tests were strongly associated with risk scores > 2 [odds ratio (OR) 10.88; 95% confidence interval (CI) 2.35-50.43], and with detected HIV-1 RNA (OR 26.06; 95% CI 3.91-173.60).ConclusionsWhen the sample occurrence of discordance between the first and second tests is below 5%, discordant rapid tests in an adult with sexual risk behaviour should trigger strong suspicion of early HIV infection in low HIV prevalence populations.

Background Although statins, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are generally well tolerated, the impact of these therapies individually or in combination on the change in neurocognitive function in persons with human immunodeficiency virus infection is unknown. Methods The study included participants in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort participants not receiving a statin or ACEI/ARB within 30 days of first neurologic assessment (baseline), with assessments by NPZ-3 (z score of averaged Trailmaking A and B tests and digit symbol test [DST]) from ≥2 measurements. Marginal structural models estimated the causal effect of statin or ACEI/ARB initiation on neurocognitive function; initial constant slope was assumed during the first year of treatment and a second constant slope thereafter. Results Of 3949 eligible participants, 16% started therapy with a statin, 11% with an ACEI/ARB, and 5% with both. Statin therapy had no significant effect on the composite NPZ-3 (primary outcome), Trailmaking B test, or DST. A small, nonsignificant positive effect on the Trailmaking A test was seen during year 1 (estimate, 0.088; 95% confidence interval, -.010 to .187; P = .08) and a small but significant negative effect (-0.033; -.058 to -.009; P = .007) in each subsequent year. ACEI/ARB therapy had a significant negative effect on the DST (-0.117; 95% confidence interval, -.217 to .016; P = .02) during year 1 but minimal effect in subsequent years or on other neurocognitive domains. Conclusions In summary, although modest declines in neurocognitive performance were seen in single domains with statin or ACEI/ARB therapy, we did not find consistent evidence that statins or ACEI/ARB have an effect on global neurocognitive function. Future studies should focus on long-term neurocognitive effects.