Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia

Background Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. Methods We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6–10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. Results Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6–10 weeks were lower among infants who were HEU vs HU [β = − 0.29 (95% CI: − 0.46, − 0.12) and [β = − 0.42 (95% CI: − 0.68, − 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = − 0.28 CI: − 0.50, − 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6–10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = − 0.30 CI: − 0.59, − 0.01)] at 6 months, without other anthropometric differences at either site. Conclusion Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.

Multi-year Use of the Standard Gauge Railway Underpasses by Mammals in Tsavo, Kenya: Influence of Underpass Dimensions, Infrastructure and Ecology

Rail and road infrastructure is essential for economic growth and development but can cause a gradual loss in biodiversity and degradation of ecosystem function and services. We assessed influence of underpass dimensions, fencing, proximity to water and roads, Normalized Difference Vegetation Index (NDVI), presence of other species and livestock on underpass use by large and medium-sized mammals. Results revealed hyenas and leopards used the underpasses more than expected whereas giraffes and antelopes used the underpasses less than expected. Generalized linear mixed effects models (GLMMs) revealed that underpass height influenced their use by wildlife, with several species preferring to use taller underpasses. Electric fencing increased underpass use by funneling species towards underpasses, except for elephants and black-backed jackal for which it reduced underpass passage. GLMMs also revealed that the use of underpasses by livestock reduced the probability of their use by nearly 50% of wildlife species. Carnivore species were more likely to cross underpasses used by their prey. Buffalo, livestock, and hyenas used underpasses with higher NDVI and near water sources while baboons, dik-diks and antelope avoided underpasses with high NDVI. The findings suggest a need for diverse, and comprehensive approach for mitigating the negative impacts of rail on African wildlife.

Evaluating sources of variability in inflorescence number, flower number and the progression of flowering in Sauvignon blanc using a Bayesian modelling framework

The time of flowering is key to understanding the development of grapevines. Flowering coincides with inflorescence initiation and fruit set, important determinants of yield. This research aimed to determine between and within-vine variability in 4-cane-pruned Sauvignon blanc inflorescence number per shoot, number of flowers per inflorescence and flowering progression using an objective method of assessing flowering via image capture and statistical analysis using a Bayesian modelling framework. The inflorescence number and number of flowers per inflorescence were measured by taking images over the flowering period. Flowering progression was assessed by counting open and closed flowers for each image over two seasons. An ordinal multinomial generalised linear mixed-effects model (GLMM) was fitted for inflorescence number, a Poisson GLMM for flower counts and a binomial GLMM for flowering progression. All the models were fitted and interpreted within a Bayesian modelling framework. Shoots arising from cane node one had lower numbers of inflorescences compared to those at nodes 3, 5 and 7, which were similar. The number of flowers per inflorescence was greater for basal inflorescences on a shoot than apical ones. Flowering was earlier, by two weeks, and faster in 2017/18 when compared to 2018/19 reflecting seasonal temperature differences. The time and duration of flowering varied at each inflorescence position along the cane. While basal inflorescences flowered later and apical earlier at lower insertion points on the shoot, the variability in flowering at each position on the vine dominated the date and duration of flowering.This is the first study using a Bayesian modelling framework to assess variability inflorescence presence and flower number, as well as flowering progression via objective quantification of open and closed flower counts rather than the more subjective method of visual estimation in the field or via cuttings. Although flower number differed for apical and basal bunches, little difference in timing and progression of flowering by these categories was observed. The node insertion point along a shoot was more important. Overall, the results indicate individual inflorescence variation and season are the key factors driving flowering variability and are most likely to impact fruit set and yield.

Trends, Variation, and Factors Influencing Antibiotic Prescribing: A Longitudinal Study in Primary Care Using a Multilevel Modelling Approach

Antimicrobial resistance has become one of the greatest threats to global health. Over 80% of antibiotics are prescribed in primary care, with many prescriptions considered to be issued inappropriately. The aim of this study was to examine the association between prescribing rates and demographic, practice, geographic, and socioeconomic characteristics using a multilevel modelling approach. Antibiotic prescribing data by 320 GP surgeries in Northern Ireland were obtained from Business Services Organisation for the years 2014–2020. A linear mixed-effects model was used to identify factors influencing antibiotic prescribing rates. Overall, the number of antibacterial prescriptions decreased by 26.2%, from 1,564,707 items in 2014 to 1,155,323 items in 2020. Lower levels of antibiotic prescribing were associated with urban practices (p < 0.001) and practices in less deprived areas (p = 0.005). The overall decrease in antibacterial drug prescriptions over time was larger in less deprived areas (p = 0.03). Higher prescribing rates were linked to GP practices located in areas with a higher percentage of the population aged ≥65 (p < 0.001) and <15 years (p < 0.001). There were also significant regional differences in antibiotic prescribing. We advocate that any future antibiotic prescribing targets should account for local factors.

Step Number and Aerobic Minute Exercise Prescription and Progression in Stroke: A Roadmap

Background While higher therapeutic intensity improves motor recovery after stroke, translating findings from successful studies is challenging without clear exercise intensity targets. We show in the DOSE trial 1 more than double the steps and aerobic minutes within a session can be achieved compared with usual care and translates to improved long-term walking outcomes. Objective We modeled data from this successful higher intensity multi-site RCT to develop targets for prescribing and progressing exercise for varying levels of walking impairment after stroke. Methods In twenty-five individuals in inpatient rehabilitation, twenty sessions were monitored for a total of 500 one-hour physical therapy sessions. For the 500 sessions, step number and aerobic minute progression were modeled using linear mixed effects regression. Using formulas from the linear mixed effects regression, targets were calculated. Results The model for step number included session number and baseline walking speed, and for aerobic minutes, session number and age. For steps, there was an increase of 73 steps per session. With baseline walking speed, for every 0.1 m/s increase, a corresponding increase of 302 steps was predicted. For aerobic minutes, there was an increase of .56 minutes of aerobic activity (ie, 34 seconds) per session. For every year increase in age, a decrease of .39 minutes (ie, 23 seconds) was predicted. Conclusions Using data associated with better walking outcomes, we provide step number and aerobic minute targets that future studies can cross-validate. As walking speed and age are collected at admission, these models allow for uptake of routine measurement of therapeutic intensity. Registration: www.clinicaltrials.gov ; NCT01915368.

An investigation of behavioural and electrophysiological markers of integration in learning of novel names for novel concepts

The Complementary Learning Systems model of word learning proposes that newly learned words that have been integrated into semantic memory can interact with familiar words during lexical selection. The study reported here is the first to examine how behavioural markers of integration map onto electrophysiological markers of integration in a version of the semantic priming paradigm that is assumed to rely primarily on automatic semantic processing. 71 young healthy adults learned novel names for two sets of novel concepts, one set on each of two consecutive days. Learning was followed by a continuous primed lexical decision task with EEG measures.The behavioural data was analysed with Bayesian Linear Mixed Effects models, while, for the electrophysiological data, two types of analyses were conducted: Bayesian Distributional Regression models were used to analyse mean amplitude in two pre-defined spatiotemporal windows (N400 and LPC), whereas the Mass Univariate analysis was run to explore other time points and regions. We found evidence against priming effects in either spatiotemporal window or in the behavioural data. Nonetheless, there was evidence for differential processing of the novel names depending on the length of the consolidation period (0-day vs 1-day). We take these findings to indicate that neither the 0-day nor the 1-day consolidation period was sufficient for integration in our study and that, 24 hours after exposure to novel words, the system still relies on episodic memory to distinguish between these novel words (learned 24h ago), those learned more recently and those that haven’t been seen before.

Association of CSF Aβ38 Levels With Risk of Alzheimer Disease–Related Decline

Objective:Experimental studies suggest that the balance between short and long Aβ species might modulate the toxic effects of Aβ in Alzheimer’s disease (AD) but clinical evidence is lacking. We studied whether Aβ38 levels in cerebrospinal fluid (CSF) relate to risk of AD dementia and cognitive decline.Methods:CSF Aβ38 levels were measured in 656 individuals across two clinical cohorts – the Swedish BioFINDER study and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cox regression models were used to evaluate the association between baseline Aβ38 levels and risk of AD dementia in AD-biomarker positive individuals (AD+; determined by CSF P-tau/Aβ42 ratio) with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Linear mixed effects models were used to evaluate the association between baseline Aβ38 levels and cognitive decline as measured by the Mini-Mental State Examination (MMSE) in AD+ participants with SCD, MCI or AD dementia.Results:In the BioFINDER cohort, high Aβ38 levels were associated with slower decline in MMSE (β = 0.30 points / sd., P = 0.001) and with lower risk of conversion to AD dementia (HR = 0.83 per sd., P = 0.03). In the ADNI cohort, higher Aβ38 levels were associated with less decline in MMSE (β = 0.27, P = 0.01), but not risk of conversion to AD dementia (P = 0.66). Aβ38 levels in both cohorts were significantly associated with both cognitive and clinical outcomes when further adjusted for CSF P-tau or CSF Aβ42 levels.Interpretation:Higher CSF Aβ38 levels are associated with lower risk of AD-related changes in two independent clinical cohorts. These findings suggest that γ-secretase modulators could be effective as disease-altering therapy.