Dual and triple therapy to prevent mother-to-child transmission of HIV in a resource-limited setting – lessons from a South African programme

Objective. To determine outcomes of pregnant women and their infants at McCord Hospital in Durban, South Africa, where dual and triple therapy to reduce HIV vertical transmission have been used since 2004 despite national guidelines recommending simpler regimens. Method. We retrospectively examined records of all pregnant women attending McCord Hospital for their first antenatal visit between 1 March 2004 and 28 February 2007. Uptake of HIV testing and HIV prevalence were determined, and clinical, immunological and virological outcomes of HIV-positive women and their infants, followed through to 6 months after delivery, were described. Results. The antenatal clinic was attended by 5 303 women; 4 891 (92%) had an HIV test, and 703 (14%) were HIV positive. The HIV-positive women were subsequently followed up: 653 (93%) received antiretroviral therapy or prophylaxis, including 424 (60%) who received triple therapy. Of the 699 live babies delivered, 661 (94%) received prophylaxis. At 6 weeks 571 babies (82%) were brought back for HIV testing; 16 (2.8%) were HIV positive. After 6 months, only 150 women (21%) were receiving follow-up care at the adult HIV clinic. Conclusion. Where a tailored approach to prevention of motherto-child transmission (PMTCT) is used, which attempts to maximise available technology and resources, good short-term transmission outcomes can be achieved. However, longer-term follow-up of mothers’ and babies’ health presents a challenge. Successful strategies to link women to ongoing care are crucial to sustain the gains of PMTCT programmes

Decision intelligence in street lighting management

The European Union has been making efforts to increase energy efficiency within its member states, in line with most of the industrialized countries. In these efforts, the energy consumed by public lighting networks is a key target as it represents approximately 50% of the electricity consumption of European cities. In this paper we propose an approach for the autonomous management of public lighting networks in which each luminary is managed individually and that takes into account both their individual characteristics as well as ambient data. The approach is compared against a traditional management scheme, leading to a reduction in energy consumption of 28%.This work is co-funded by Fundos Europeus Estruturais e de Investimento (FEEI) through Programa Operacional Regional Norte, in the scope of project NORTE01-0145-FEDER-023577 and by national funds through FCT – Fundação para a Ciência e Tecnologia through projects UID/CEC/00319/2019 and UIDB/04728/2020

The Imprint of Galaxy Formation on X-ray Clusters

It is widely believed that structure in the Universe evolves hierarchically, as primordial density fluctuations, amplified by gravity, collapse and merge to form progressively larger systems. The structure and evolution of X-ray clusters, however, seems at odds with this hierarchical scenario for structure formation. Poor clusters and groups, as well as most distant clusters detected to date, are substantially fainter than expected from the tight relations between luminosity, temperature and redshift predicted by these models. Here we show that these discrepancies arise because, near the centre, the entropy of the hot, diffuse intracluster medium (ICM) is higher tha$achievable through gravitational collapse, indicating substantial non-gravitational heating of the ICM. We estimate this excess entropy for the first time, and argue that it represents a relic of the energetic winds through which forming galaxies polluted the ICM with metals. Energetically, this is onl$ possible if the ICM is heated at modest redshift (z \ltsim 2) but prior to cluster collapse, indicating that the formation of galaxies precedes that of clusters and that most clusters have been assembled very recently.Comment: 5 pages, plus 2 postscript figures (one in colour), accepted for publication in Natur

Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways

Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context

Device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients

BACKGROUND: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection. OBJECTIVE: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population. METHODS: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (7/2016-12/2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a p≤0.25 for inclusion in a multivariable model and a backwards, stepwise elimination process with p≤0.1 to remain in the model. A time-to-event analysis was also conducted. RESULTS: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post-implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus. CONCLUSION: The rate of de novo TV-ICD infection was 1.9% and identified risk factors associated with infection may be useful in device selection

Impact of foot-and-mouth disease on mastitis and culling on a large-scale dairy farm in Kenya

Foot and mouth disease (FMD) is a highly transmissible viral infection of cloven hooved animals associated with severe economic losses when introduced into FMD-free countries. Information on the impact of the disease in FMDV-endemic countries is poorly characterised yet essential for the prioritisation of scarce resources for disease control programmes. A FMD (virus serotype SAT2) outbreak on a large-scale dairy farm in Nakuru County, Kenya provided an opportunity to evaluate the impact of FMD on clinical mastitis and culling rate. A cohort approach followed animals over a 12-month period after the commencement of the outbreak. For culling, all animals were included; for mastitis, those over 18 months of age. FMD was recorded in 400/644 cattle over a 29-day period. During the follow-up period 76 animals were culled or died whilst in the over 18 month old cohort 63 developed clinical mastitis. Hazard ratios (HR) were generated using Cox regression accounting for non-proportional hazards by inclusion of time-varying effects. Univariable analysis showed FMD cases were culled sooner but there was no effect on clinical mastitis. After adjusting for possible confounders and inclusion of time-varying effects there was weak evidence to support an effect of FMD on culling (HR = 1.7, 95% confidence intervals [CI] 0.88-3.1, P = 0.12). For mastitis, there was stronger evidence of an increased rate in the first month after the onset of the outbreak (HR = 2.9, 95%CI 0.97-8.9, P = 0.057)

Aerosols implicated as a prime driver of twentieth-century North Atlantic climate variability

Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean1. These links are extensive, influencing a range of climate processes such as hurricane activity2 and African Sahel3, 4, 5 and Amazonian5 droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations6, 7, 8, 9, 10. A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures11, 12, but climate models have so far failed to reproduce these interactions6, 9 and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860–2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910–1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol–cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol–cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; &lt;4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Silver hake tracks changes in Northwest Atlantic circulation

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Communications 2 (2011): 412, doi:10.1038/ncomms1420.Recent studies documenting shifts in spatial distribution of many organisms in response to a warming climate highlight the need to understand the mechanisms underlying species distribution at large spatial scales. Here we present one noteworthy example of remote oceanographic processes governing the spatial distribution of adult silver hake, Merluccius bilinearis, a commercially important fish in the Northeast US shelf region. Changes in spatial distribution of silver hake over the last 40 years are highly correlated with the position of the Gulf Stream (GS). These changes in distribution are in direct response to local changes in bottom temperature on the continental shelf that are responding to the same large scale circulation change affecting the GS path, namely changes in the Atlantic Meridional Overturning Circulation (AMOC). If AMOC weakens as is suggested by global climate models, silver hake distribution will remain in a poleward position, the extent to which could be forecast at both decadal and multidecadal scales.J.A.N. was supported by the NOAA Fisheries and the Environment program (FATE). T.M.J. and Y.O.K. were supported by the WHOI Ocean Climate Change Institute and Ocean Life Institute