Latching dynamics as a basis for short-term recall

We discuss simple models for the transient storage in short-term memory of cortical patterns of activity, all based on the notion that their recall exploits the natural tendency of the cortex to hop from state to state—latching dynamics. We show that in one such model, and in simple spatial memory tasks we have given to human subjects, short-term memory can be limited to similar low capacity by interference effects, in tasks terminated by errors, and can exhibit similar sublinear scaling, when errors are overlooked. The same mechanism can drive serial recall if combined with weak order-encoding plasticity. Finally, even when storing randomly correlated patterns of activity the network demonstrates correlation-driven latching waves, which are reflected at the outer extremes of pattern space

Correction to: Clinical management of ageing people living with HIV in Europe: the view of the care providers.

info:eu-repo/semantics/publishedVersio

Parous women perform less moderate to vigorous physical activity than their nulliparous peers: a population-based study in Denmark

Objectives The World Health Organization (WHO) highlights parous women as a key population for monitoring trends of physical activity (PA). We aimed to estimate the proportion of Danish women non-adhering to WHO PA guidelines in parous women compared with nulliparous women and to describe leisure-time PA intensity in each of these groups. Study design Cross-sectional study. Methods This population-based study builds on a sample of 27,668 women aged 16–40 years from the Danish National Health Survey 2021. These data were linked with childbirth data from the Danish National Birth Registry. The primary outcome was self-reported weekly hours of moderate to vigorous leisure-time PA (MVPA) dichotomized into: (i) adhering to WHO guidelines for MVPA or (ii) not adhering to WHO guidelines for MVPA. Binomial regression analysis was used to calculate prevalence proportions (PP) and prevalence proportion ratios (PPR). Results Of the 27,668 women, a total of 20,022 were included; 9338 (46.6%) parous women and 10,684 (53.4%) nulliparous women. The PP of women non-adhering to WHO PA guidelines was 63.8% (95% CI 62.9–64.8) for parous and 51.3% (95% CI 50.4–52.3) for nulliparous women, corresponding to a PPR of 1.24 (95% CI 1.21; 1.27). Conclusions The proportion of parous women who did not adhere to WHO PA guidelines for MVPA was 24% higher than that of nulliparous women. This highlights parous women as a subgroup of the adult population at increased risk of non-adherence to WHO PA guidelines. These findings call for future research to inform new strategies aiming to promote PA in parous women

Effect of Changes in Body Mass Index on the Risk of Cardiovascular Disease and Diabetes Mellitus in HIV-Positive Individuals: Results From the D:A:D Study

BACKGROUND: Weight gain is common among people with HIV once antiretroviral treatment (ART) is commenced. We assess the effect of changes in body mass index (BMI), from different baseline BMI levels, on the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). METHODS: D:A:D participants receiving ART were followed from their first BMI measurement to the first of either CVD or DM event, or earliest of 1/2/2016 or 6 months after last follow-up. Participants were stratified according to their baseline BMI, and changes from baseline BMI were calculated for each participant. Poisson regression models were used to assess the effects of changes on BMI on CVD or DM events. RESULTS: There were 2,104 CVD and 1,583 DM events over 365,287 and 354,898 person years (rate: CVD 5.8/1000 (95% CI 5.5-6.0); DM 4.5/1000 (95% CI 4.2 - 4.7)). Participants were largely male (74%), baseline mean age of 40 years and median BMI of 23.0 (IQR: 21.0-25.3). Risk of CVD by change in BMI from baseline, stratified by baseline BMI strata showed little evidence of an increased risk of CVD with an increased BMI in any baseline BMI strata. An increase in BMI was associated with an increased risk of DM across all baseline BMI strata. CONCLUSIONS: While increases in BMI across all levels of baseline BMI were not associated with an increased risk of CVD, such changes were consistently associated with increased risk of DM. There was also some evidence of an increased risk of CVD with a decrease in BMI

Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting

Background: Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. Methods: Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. Results: Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36-51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9-7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3-7.1). The commonest cancers were non-Hodgkin lymphoma (n=113), lung cancer (112), Kaposi's sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89-1.49], >6-12 months; 0.97 [95% CI, 0.71-1.32], >12-24 months; 0.84 [95% CI, 0.64-1.11], >24-36 months; 1.10 [95% CI, 0.82-1.47], >36 months; 0.90 [95% CI, 0.65-1.26] [P=.60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P<.0001). Conclusions: Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding

Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium

Objectives: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. Methods: Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL. Results: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67–0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97–1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71–0.91], p<0.001) and PI/b (0.87 [CI 0.76–0.99], p = 0.04). Conclusion: In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes

The football is medicine plaform-scientific evidence, large-scale implementation of evidence-based concepts and future perspectives

The idea that football can be used as therapy and as a high-intensity and literally breath-taking training regime goes back centuries. To take one prominent example, the French philosopher Voltaire describes in the Book of Fate (1747), how a patient is cured by playing with a sacred football: “… full-blown and carefully covered with the softest Leather. You must kick this Bladder, Sir, once a Day about your Hall for a whole Hour together, with all the Vigour and Activity you possibly can”, “Ogul, upon making the first Experiment, was ready to expire for want of Breath”, “In short, our Doctor in about 8 days Time, performed an absolute Cure. His Patient was as brisk, active and gay, as One in the Bloom of his Youth.”1 Today, Voltaire and his main character, philosopher Zadig, have been proved right: Football is indeed a breath-taking activity and it can be used as therapy. Albeit today's recommendations suggest a lower training frequency, longer training periods and encourage group-based training, and say that any football can be applied

Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium

BACKGROUND: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. METHODS: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. RESULTS: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively). INTERPRETATION: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences

Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: From treatment to prevention

The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being