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Abstract Normal pressure hydrocephalus (NPH) is associated with a reduction in cerebral blood flow and an ischemic metabolic state. Ischemia should exhaust the available autoregulation in an attempt to correct the metabolic imbalance. There is evidence of some retained autoregulation reserve in NPH. The aim of this study is to model the cerebral autoregulation in NPH to discover a solution to this apparent paradox. A lumped parameter model was developed utilizing the known limits of autoregulation in man. The model was tested by predicting the cerebral blood volume changes which would be brought about by changes in resistance. NPH and the post shunt state were then modeled using the known constraints provided from the literature. The model successfully predicted the cerebral blood volume changes brought about by altering the cerebral perfusion pressure to the limit of autoregulation. The model suggests that NPH is associated with a balanced increase in resistance within the arterial and venous outflow segments. The arterial resistance decreased after modelling shunt insertion. The model suggests that the cerebral blood flow is actively limited in NPH by arteriolar constriction. This may occur to minimize the rise in ICP by reducing the apparent CSF formation rate.

AbstractThe entrepreneurship field is increasingly interlaced with diverse disciplines, tackling complex societal issues from sustainability to digitalization and family business dynamics. Recognizing the necessity to steer future research, the editorial team of Cogent Business and Management’s Entrepreneurship and Innovation section present ten research domains identified through collective expertise. These areas, ranging from corporate innovation to entrepreneurship education and transitional entrepreneurship, are critical for academic investigation and hold potential for significant societal impact. These domains are not intended to constitute a ‘top 10’ list, nor are they exhaustive; rather, they are intended to help guide scholars toward research domains we believe are ripe for exploration and with the potential to be highly impactful. These domains embody the field’s ever-evolving nature, encapsulating the entrepreneurial spirit as a quilt of interconnected patches rather than isolated pieces. They encourage an interdisciplinary approach, highlighting the need for a comprehensive understanding of entrepreneurial activity. As the entrepreneurship literature grows, its adaptability will be crucial for theoretical advancement and practical applications. The proposed research roadmap aims to ignite cross-disciplinary dialogue, driving the impact of entrepreneurship research beyond academic circles and into the realms of policy and practice.

Abstract Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. Previously, the current authors have discussed the similarities and differences between SANS and idiopathic intracranial hypertension to try to elucidate a possible pathophysiology. Recently, a theory has been advanced that SANS may occur secondary to failure of the glymphatic system caused by venous dilatation within the brain and optic nerves. There is recent evidence to suggest glymphatic obstruction occurs in childhood hydrocephalus, multiple sclerosis and syringomyelia due to venous outflow dilatation similar to that proposed in SANS. The purpose of the current paper is to discuss the similarities and differences between the known CSF and venous pathophysiology in SANS with these other terrestrial diseases, to see if they can shed any further light on the underlying cause of this microgravity-induced disease.

Abstract Senecavirus A (SVA) causes vesicular disease in swine and has been responsible for a rampant increase in the yearly number of foreign animal disease investigations conducted in the United States. Diagnostic investigations for SVA are typically performed by sampling animals individually, which is labor-intensive and stressful. Developing an alternative aggregate sampling method would facilitate the detection of this virus at the population level. In a preliminary study, SVA was detected in processing fluids (PF) collected in a breeding herd before and after outbreak detection. The objective of this study was to estimate the average number of weeks PF remain SVA-positive after an SVA outbreak. Ten farrow-to-wean breeding herds volunteered to participate in this studyby longitudinally collecting PF samples after an SVA outbreak was detected and submitting samples for RT-rtPCR testing. The PF samples from the 10 farms were SVA-positive for an average of 11.8 weeks after the outbreak. Here, we show that testing of PF may be a cost-effective method to detect SVA and help halt its spread in SVA-endemic regions.

A comprehensive aircraft survey of onshore oil and gas infrastructure in British Columbia finds that methane emissions may be 1.7 times higher than the official inventory and introduces a framework for compiling measurement-led regional greenhouse gas emissions data.

Abstract The cross-sectional area of the superior sagittal sinus (SSS) is larger in multiple sclerosis than normal and correlates with disease severity and progression. The sinus could be enlarged due to a decrease in the pressure difference between the lumen and the subarachnoid space, an increase in wall thickness or increased wall stiffness. The cross-sectional area of the SSS and straight sinus (ST) were measured in 103 patients with multiple sclerosis and compared to 50 controls. The cross-sectional area of the SSS and ST were increased by 20% and 13% compared to the controls (p = 0.005 and 0.02 respectively). The deflection of the wall of the sinus was estimated. The change in pressure gradient, wall thickness or elastic modulus between groups was calculated by modelling the walls as simply supported beams. To account for these findings, the modelling suggests either a 70% reduction in transmural venous pressure or a 2.4 fold increase in SSS wall stiffness plus an 11% increase in wall thickness or a combination of changes. An increase in sinus pressure, although the most straight forward possibility to account for the change in sinus size may exist in only a minority of patients. An increase in sinus wall stiffness and thickness may need further investigation.

Abstract Spaceflight associated neuro-ocular syndrome (SANS) alters the vision of astronauts during long-duration spaceflights. There is controversy regarding SANS being similar to patients with idiopathic intracranial hypertension (IIH). IIH has been shown to be due to an elevation in venous sinus pressure. The literature suggests an increase in jugular vein pressure secondary to a headward shift of fluid occurs in SANS but this may not be enough to significantly alter the intracranial pressure (ICP). The literature regarding cardiac output and cerebral blood flow (CBF) in long-duration spaceflight is contradictory, however, more recent data suggests increased flow. Recent modelling has shown that an increase in CBF can significantly increase sinus pressure. The purpose of the present paper is to review the SANS vascular dynamics literature and through mathematical modelling suggest the possible underlying cause of SANS as an elevation in venous sinus pressure, secondary to the redistribution of fluids towards the head, together with a significant increase in pressure drop across the venous system related to the CBF.

COVID-19 has led to an unprecedented disruption in tourism spending. This has propagated through the whole economy, however the scale of these system-wide consequences can be hard to quantify. We calculate direct reductions in spending across domestic and inbound tourism categories and then use a computable general equilibrium model to quantify their economic impacts. The results – illustrated using a model for Scotland and focusing on 2021 - demonstrate the scale of the losses in the tourism industry and the economy as a whole that are attributable to changes in both domestic and inbound tourism demand. We find that the extent to which domestic tourism demand can mitigate the losses in inbound spending depends on the composition of demand.

Abstract As well as their role in contributing towards emissions reductions targets, it is increasingly relevant for policymakers to understand the contribution that renewable energy technologies make to the economy. Various methods have been used to quantify impacts, such as job counts, surveys and measures based on economic statistics. Economic modelling approaches on the other hand appear to offer an ability to both provide metrics of interest to policymakers and crucially an understanding of the activities which support that contribution. In this paper, we implement a new method for estimating the activity supported by renewable energy activities; applying a ‘hypothetical extraction’ of offshore wind—to identify the contribution that such activities make to U.K. economic activity, job quality and national emissions. By undertaking the partial extraction of offshore wind from an aggregated input–output (IO) table and then subsequently from one in which we have separated out the offshore wind electricity sector, we highlight the value of more disaggregation and technology‐specific detail in economic accounts. The results from our fullest extraction suggest that in 2010, offshore wind in the United Kingdom supported 10 240 jobs, with 9 in 10 of these jobs either medium or high skill, and contributed £780 million to gross domestic product (GDP). In addition, a significant portion of activity supported by offshore wind is attributable to expansions in capacity rather than operational activities.

Abstract Background It has been shown that idiopathic intracranial hypertension (IIH) in children is associated with cerebral hyperemia, which induces an increase in cerebral venous pressure. The current literature suggests venous pressure scales with blood flow in a linear fashion, however, a linear relationship would not raise the pressure high enough to induce IIH. There is, however, some evidence to suggest that this relationship could be quadratic in nature. The purpose of this paper is to characterize the relationship between cerebral blood flow and the pressure drop across the cerebral venous system. Methods 10 CT venogram data sets were collected for this study, with 5 useable geometries created. Computational fluid dynamics (CFD) models were generated using these geometries, with 10 simulations conducted per patient. The flow rates tested ranged from 200 mL/min to 2000 mL/min. 3D pressure and velocity streamline distributions were created and analyzed for each CFD model, with pressure drops across the cerebral venous system determined. The effective and hydraulic diameters were determined at the superior sagittal sinus, transverse sinus and both proximal and distal sigmoid sinuses. Results A quadratic relationship between blood flow and sinus pressure was found, with correlations of 0.99 or above in all five patients. The presence of vortical blood flow was found to explain this trend, with fluid curl and pressure drop correlations being above 0.97. This suggests that the presence of high blood flow should be considered in the diagnostic workup of IIH. Conclusions The cerebral venous sinus blood flow and pressure response relationship are quadratic in nature, with the major cause of this being the degree of rotation induced in the flow. The elevated blood flow found in children with IIH can explain the increased ICP that is found, secondary to the increase in venous pressure that develops.

The female perspective of implementing failure learning orientation is explored through the analysis of interviews with Canadian female executives of technology firms. The results of this study established several strategies for executives to use for creating an organizational culture that learns from failure. The strategies include, reimagine failure to mitigate negative emotions, focus on the root of the issue, openly discuss strategies and failures, be proactive, encourage risk-taking in experimentation, and finally, provide a calming presence.

Abstract Background Children referred to a tertiary hospital for the indication, “rule out idiopathic intracranial hypertension (IIH)” may have an increased risk of raised venous sinus pressure. An increase in sinus pressure could be due to obesity, venous outflow stenosis or cerebral hyperemia. The purpose of this paper is to define the incidence of each of these variables in these children. Methods Following a data base review, 42 children between the ages of 3 and 15 years were found to have been referred over a 10 year period. The body mass index was assessed. The cross sectional areas and circumferences of the venous sinuses were measured at 4 levels to calculate the hydraulic and effective diameters. The arterial inflow, sagittal and straight sinus outflows were measured. Automatic cerebral volumetry allowed the brain volume and cerebral blood flow (CBF) to be calculated. The optic nerve sheath diameter was used as a surrogate marker of raised intracranial pressure (ICP). The sagittal sinus percentage venous return was used as a surrogate marker of elevated venous pressure. Age and sex matched control groups were used for comparison. Results Compared to controls, the obesity rates were not significantly different in this cohort. Compared to controls, those at risk for IIH had a 17% reduction in transverse sinus and 14% reduction in sigmoid sinus effective cross sectional area (p = 0.005 and 0.0009). Compared to controls, the patients at risk for IIH had an arterial inflow increased by 34% (p

Abstract Background Symptomatic or active hydrocephalus in children is linked to an elevation in intracranial pressure (ICP), which is likely to be multifactorial in origin. The CSF outflow resistance, venous sinus resistance and total cerebral blood flow are likely factors in the ICP elevation. The purpose of this paper is to define the incidence, site and significance of venous sinus stenosis and/or cerebral hyperemia in a cohort of children diagnosed with hydrocephalus at a tertiary referral hospital. Methods The imaging database was reviewed over a 10 year period and the index MRI of all children between the ages of 4 months and 15 years, who were diagnosed with treatment naive hydrocephalus of any type (excluding secondary to tumor) and had magnetic resonance venography (MRV) and flow quantification were selected. Patients were compared with children undergoing an MRI with MRV and flow quantification who were subsequently shown to have no abnormality. The cross-sectional area and circumference of the sinuses were measured at 4 levels. The hydraulic and effective diameters were calculated. An area stenosis of 65% or greater was deemed significant. A total cerebral blood flow greater than two standard deviations above the mean for controls was taken to be abnormal. Results There were a total of 55 children with hydrocephalus compared to 118 age matched control MRV’s and 35 control flow quantification studies. A high grade stenosis occurred in 56% of patients but in none of the controls (p

Bioaerosols often contain human pathogens and allergens affecting public health. However, relatively little attention has been given to bioaerosols compared with non-biological aerosols. In this study, we aimed to identify bioaerosol compositions in Manchester, UK by applying high throughput sequencing methods and to find potential sources. Samples were collected at Manchester Air Quality Super Site at the Firs Environmental Research Station in November 2019 and in February 2020. Total DNA has been extracted and sequenced targeting the 16S rRNA gene of prokaryotes, ITS region of fungal DNA and 18S rRNA gene of eukaryotes. We found marine environment-associated bacteria and archaea were relatively more abundant in the February 2020 samples compared with the November 2019 samples, consistent with the North West marine origin based on wind back-trajectory analysis. In contrast, an OTU belonging to Methylobacterium, which includes many species resistant to heavy metals, was relatively more abundant in November 2019 when there were higher metal concentrations. Fungal taxa that fruit all year were relatively more abundant in the February 2020 samples while autumn fruiting species generally had higher relative abundance in the November 2019 samples. There were higher relative abundances of land plants and algae in the February 2020 samples based on 18S rRNA gene sequencing. One of the OTUs belonging to the coniferous yew genus Taxus was more abundant in the February 2020 samples agreeing with the usual pollen season of yews in the UK which is from mid-January until late April. The result from this study suggests a potential application of bioaerosol profiling for tracing the source of atmospheric particles.

Resistive switching is of the key phenomena for applications such as nonvolatile memories or neuromorphic computing. V_{3}O_{5}, a compound of the vanadium oxide Magnéli series, is one of the rare materials to exhibit an insulator-metal transition above room temperature (T_{c}∼415 K). The switching mechanisms in this material are still not clear. Here, we demonstrate both static dc volatile resistive switching and fast oscillatory spiking regimes in V_{3}O_{5} devices at room temperature (120 K below the phase transition temperature) by applying an electric field. We couple electrical measurements, operando optical imaging, and infrared measurements to track the reflectivity change and the temperature of a device during the resistive switching. We find that the resistive switching starts via thermal runaway deep in the insulating state and triggers the phase transition with the formation of a filament of the high-temperature phase. Furthermore, we capture optically and thermally the spiking oscillations that we link to the negative differential resistance regime and find the filament forms and dissolves via a periodic spatiotemporal instability that we describe by numerical simulations. Our studies play an important role in understanding the volatile resistive switching mechanisms and demonstrate that V_{3}O_{5} can be a key vanadium oxide for neuromorphic computing.

There is an expectation that many cities in Australia may experience higher temperatures and reduced rainfall in the future. Hence, to support water policy analysis there is a need for predicting water demand and how it changes in response to climate change. This paper describes a methodology to develop a model that explains month-to-month variability in water demand due to climate and weather, on the basis of using statistical methods. To achieve this, we use time series data of historical water use volumes and climate data from relevant weather stations. Applying this model together with hypothetical climate change scenarios, but without community adaptation scenarios, the results indicate that water demand will change moderately and, as may be expected, it is most sensitive to evaporation and temperature, followed by rainfall. With such scenarios, demand is shown to increase by as much as 10-20%, but more realistic climate sequences are required to provide reliable estimates. Given availability of data, this statistical method can be used to support policy analyses in other cities. [ABSTRACT FROM AUTHOR]

Abstract Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer’s disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice. Recently, we have designed a small peptoid library derived from the Aβ12-28 P sequence to screen for new apoE/Aβ binding inhibitors with higher efficacy and safety. Peptoids are better drug candidates than peptides due to their inherently more favorable pharmacokinetic properties. One of the lead peptoid compounds, CPO_Aβ17–21 P, diminished the apoE/Aβ interaction and attenuated the apoE4 pro-fibrillogenic effects on Aβ aggregation in vitro as well as apoE4 potentiation of Aβ cytotoxicity. CPO_Aβ17–21 P reduced Aβ-related pathology coupled with cognitive improvements in an AD APP/PS1 transgenic mouse model. Our study suggests the non-toxic, non-fibrillogenic peptoid CPO_Aβ17–21 P has significant promise as a new AD therapeutic agent which targets the Aβ related apoE pathway, with improved efficacy and pharmacokinetic properties.

Astroviruses (AstVs) cause disease in a wide variety of species. Porcine AstVs are highly genetically diverse and conventionally assigned to five genetic lineages (PoAstV1-5). Due to the increasing evidence that porcine astrovirus type 3 (PoAstV3) is a cause of encephalomyelitis in swine and to elucidate important ecologic characteristics, the infection dynamics and environmental distribution of PoAstV3 were investigated in a herd with PoAstV3-associated neurologic disease. Over a 22 week period, the frequency of PoAstV3 fecal shedding varied by pig and age. The peak detection by RT-qPCR of PoAstV3 on fecal swabs (95%; 61 of 64) occurred at 3 weeks of age. The lowest frequency of detection was at 21 weeks of age (4%; 2 of 47); however, the frequency increased to 41% (19 of 46) at the final sampling time point (25 weeks of age). Viremia was rare (0.9%: 4 of 433). Detection in oral fluid was consistent with 75% to 100% of samples positive at each time point. Pens and feeders also had a high rate of detection with a majority of samples positive at a majority of sampling time points. Based on the data presented, PoAstV3 can be consistently detected in the environment with a majority of pigs being infected and a subset intermittently shedding the virus in feces out to 25 weeks of age. These findings suggest the importance of as-yet unidentified risk factors associated with the development of PoAstV3-associated polioencephalomyelitis.

Primary biological aerosols often include allergenic and pathogenic microorganisms posing potential risks to human health. Moreover, there are airborne plant and animal pathogens that may have ecological and economic impact. In this study, we used high-throughput sequencing techniques (Illumina, MiSeq) targeting the 16S rRNA genes of bacteria and the 18S rRNA genes of eukaryotes, to characterize airborne primary biological aerosols. We used a filtration system on the UK Facility for Airborne Atmospheric Measurements (FAAM) research aircraft to sample a range of primary biological aerosols across southern England overflying surface measurement sites from Chilbolton to Weybourne. We identified 30 to 60 bacterial operational taxonomic units (OTUs) and 108 to 224 eukaryotic OTUs per sample. Moreover, 16S rRNA gene sequencing identified significant numbers of genera that have not been found in atmospheric samples previously or only been described in limited number of atmospheric field studies, which are rather old or published in local journals. This includes the genera Gordonia, Lautropia, and Psychroglaciecola. Some of the bacterial genera found in this study include potential human pathogens, for example, Gordonia, Sphingomonas, Chryseobacterium, Morganella, Fusobacterium, and Streptococcus. 18S rRNA gene sequencing showed Cladosporium to be the major genus in all of the samples, which is a well-known allergen and often found in the atmosphere. There were also genetic signatures of potentially allergenic taxa; for example, Pleosporales, Phoma, and Brassicales. Although there was no significant clustering of bacterial and eukaryotic communities depending on the sampling location, we found meteorological factors explaining significant variations in the community composition. The findings in this study support the application of DNA-based sequencing technologies for atmospheric science studies in combination with complementary spectroscopic and microscopic techniques for improved identification of primary biological aerosols.

Astroviruses cause disease in a variety of species. Yet, little is known about the epidemiology of a majority of astroviruses including porcine astrovirus type 3 (PoAstV3), which is a putative cause of polioencephalomyelitis in swine. Accordingly, a cross-sectional study was conducted on sow farms with or without reported PoAstV3-associated neurologic disease in growing pigs weaned from those farms. Additionally, a conveniently selected subset of piglets from one farm was selected for gross and histologic evaluation. The distribution of PoAstV3 in the enteric system was evaluated through in situ hybridization. PoAstV3, as detected by RT-qPCR on fecal samples, was frequently detected across sows and piglets (66−90%) on all farms (65−85%). PoAstV3 was detected subsequently at a similar detection frequency (77% vs 85%) on one farm after three months. Viral shedding, as determined by the cycle quantification value, suggests that piglets shed higher quantities of virus than adult swine. No link between gastrointestinal disease and PoAstV3 was found. However, PoAstV3 was detected by in situ in myenteric plexus neurons of piglets elucidating a possible route of spread of the virus from the gastrointestinal tract to the central nervous system. These data suggest PoAstV3 has endemic potential, is shed in the feces at greater quantities by suckling piglets when compared to sows, and infection is widespread on farms in which it is detected.

Point-source methane emission flux quantification is required to help constrain the global methane budget. Facility-scale fluxes can be derived using in situ methane mole fraction sampling, near-to-source, which may be acquired from an unmanned aerial vehicle (UAV) platform. We test a new non-dispersive infrared methane sensor by mounting it onto a small UAV, which flew downwind of a controlled methane release. Nine UAV flight surveys were conducted on a downwind vertical sampling plane, perpendicular to mean wind direction. The sensor was first packaged in an enclosure prior to sampling which contained a pump and a recording computer, with a total mass of 1.0 kg. The packaged sensor was then characterised to derive a gain factor of 0.92 ± 0.07, independent of water mole fraction, and an Allan deviation precision (at 1 Hz) of ±1.16 ppm. This poor instrumental precision and possible short-term drifts made it non-trivial to define a background mole fraction during UAV surveys, which may be important where any measured signal is small compared to sources of instrumental uncertainty and drift. This rendered the sensor incapable of deriving a meaningful flux from UAV sampling for emissions of the order of 1 g s−1. Nevertheless, the sensor may indeed be useful when sampling mole fraction enhancements of the order of at least 10 ppm (an order of magnitude above the 1 Hz Allan deviation), either from stationary ground-based sampling (in baseline studies) or from mobile sampling downwind of sources with greater source flux than those observed in this study. While many methods utilising low-cost sensors to determine methane flux are being developed, this study highlights the importance of adequately characterising and testing all new sensors before they are used in scientific research.

The accurate quantification of methane emissions from point sources is required to better quantify emissions for sector-specific reporting and inventory validation. An unmanned aerial vehicle (UAV) serves as a platform to sample plumes near to source. This paper describes a near-field Gaussian plume inversion (NGI) flux technique, adapted for downwind sampling of turbulent plumes, by fitting a plume model to measured flux density in three spatial dimensions. The method was refined and tested using sample data acquired from eight UAV flights, which measured a controlled release of methane gas. Sampling was conducted to a maximum height of 31 m (i.e. above the maximum height of the emission plumes). The method applies a flux inversion to plumes sampled near point sources. To test the method, a series of random walk sampling simulations were used to derive an NGI upper uncertainty bound by quantifying systematic flux bias due to a limited spatial sampling extent typical for short-duration small UAV flights (less than 30 min). The development of the NGI method enables its future use to quantify methane emissions for point sources, facilitating future assessments of emissions from specific source-types and source areas. This allows for atmospheric measurement-based fluxes to be derived using downwind UAV sampling for relatively rapid flux analysis, without the need for access to difficult-to-reach areas.

Computation is a central aspect of 21st century physics practice; it is used to model complicated systems, to simulate impossible experiments, and to analyze mountains of data. Physics departments and their faculty are increasingly recognizing the importance of teaching computation to their students. We recently completed a national survey of faculty in physics departments to understand the state of computational instruction and the factors that underlie that instruction. The data collected from the faculty responding to the survey included a variety of scales, binary questions, and numerical responses. We then used random forest, a supervised learning technique, to explore the factors that are most predictive of whether a faculty member decides to include computation in their physics courses. We find that experience using computation with students in their research, or lack thereof and various personal beliefs to be most predictive of a faculty member having experience teaching computation. Interestingly, we find demographic and departmental factors to be less useful factors in our model. The results of this study inform future efforts to promote greater integration of computation into the physics curriculum as well as comment on the current state of computational instruction across the United States.

Energy efficiency improvements and rebound effects: some lessons from the Scottish case.

About 30 million people in Africa are estimated to be living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), yet data about the natural history of infection on the continent are sparse. We reviewed the literature on the natural history of HIV-1 and HIV-2 infections among African adults. Only one study, conducted in rural Uganda, has reported on survival from the time of HIV-1 seroconversion: the median was 9.8 years, which is similar to that reported in developed countries in the early stages of the epidemic and consistent with the findings from the follow-up of individuals identified by serological testing during community-based prevalence studies from Africa. Progression to symptomatic disease was faster in Uganda than in developed countries, due largely to the high background level of morbidity. Various studies suggest that people infected with HIV-2 survive longer and the course of the disease is possibly more variable than in people infected with HIV-1. However no studies have investigated survival from time of seroconversion among people infected with HIV-2. The majority of patients in hospital in Africa with either HIV-1 or HIV-2 have the clinical features of AIDS just before they die, and many are severely immunosuppressed. This is similar to the situation in developed countries before the introduction of highly active antiretroviral therapy (HAART). Potentially preventable infections are the leading causes of death among individuals infected with HIV-1. Prophylactic regimens and better treatments could have some effect on survival, but major improvements in life expectancy will require HAART.

This study presents the first gaseous formic acid (HC(O)OH) concentration measurements collected over the Fenno-Scandinavian wetlands (67.9–68.0° N, 22.1–27.8° E) as part of the MAMM (Methane and other greenhouse gases in the Arctic-Measurements, process studies and Modelling) aircraft campaigns conducted in August and September 2013. A boundary layer box model approach has been used to calculate a regionally representative (~240 km2) surface flux for HC(O)OH of 0.0098 (±0.0057) mg[HCOOH]·m−2·h−1. A surface-type classification map was used to estimate proportional source contributions to the observed HC(O)OH flux over the measurement region. The removal of expected source contributions (using available literature parameterisations) from the calculated surface flux identified that 75% remained unaccounted for. This may suggest that HC(O)OH emission from wetland within the Fenno-Scandinavian region could contribute up to 29 times higher per unit area than previous theoretical HC(O)OH globally-averaged wetland estimates, highlighting a need for further constrained wetland studies of HC(O)OH emission to better understand its potentially significant impact on the Arctic HC(O)OH budget and consequent impacts on oxidative capacity.

Abstract The impact of increased national wealth, as measured by Gross Domestic Product (GDP), on public health is widely understood, however an equally important but less well-acclaimed relationship exists between improvements in health and the growth of an economy. Communicable diseases such as HIV, TB, Malaria and the Neglected Tropical Diseases (NTDs) are impacting many of the world's poorest and most vulnerable populations, and depressing economic development. Sickness and disease has decreased the size and capabilities of the workforce through impeding access to education and suppressing foreign direct investment (FDI). There is clear evidence that by investing in health improvements a significant increase in GDP per capita can be attained in four ways: Firstly, healthier populations are more economically productive; secondly, proactive healthcare leads to decrease in many of the additive healthcare costs associated with lack of care (treating opportunistic infections in the case of HIV for example); thirdly, improved health represents a real economic and developmental outcome in-and-of itself and finally, healthcare spending capitalises on the Keynesian 'economic multiplier' effect. Continued under-investment in health and health systems represent an important threat to our future global prosperity. This editorial calls for a recognition of health as a major engine of economic growth and for commensurate investment in public health, particularly in poor countries.

Abstract Background Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence. Methods Treatment-naïve patients starting ART were enrolled from a community and a workplace ART programme. Potential baseline predictors associated with poor treatment outcomes (defined as viral load > 400 copies/ml or having discontinued treatment by six months) were assessed using logistic regression. Exposure variables were organised for regression analysis using a hierarchical framework. Results 38/227 (17%) of participants in the community had poor treatment outcomes compared to 47/117 (40%) in the workplace. In the community, predictors of worse outcomes included: drinking more than 20 units of alcohol per week, having no prior experience of chronic medications, and consulting a traditional healer in the past year (adjusted odds ratio [aOR] 15.36, 95% CI 3.22-73.27; aOR 2.30, 95%CI 1.00-5.30; aOR 2.27, 95% CI 1.00-5.19 respectively). Being male and knowing someone on ART were associated with better outcomes (aOR 0.25, 95%CI 0.09-0.74; aOR 0.44, 95%CI 0.19-1.01 respectively). In the workplace, predictors of poor treatment outcomes included being uncertain about the health effects of ART and a traditional healer's ability to treat HIV (aOR 7.53, 95%CI 2.02-27.98; aOR 4.40, 95%CI 1.41-13.75 respectively). Longer pre-ART waiting time (2-12 weeks compared to Conclusion Baseline predictors of poor treatment outcomes were largely unique to each programme, likely reflecting different populations and pathways to HIV care. In the workplace, active promotion of HIV testing may have extended ART to individuals who, without provider initiation, would not have spontaneously sought care. As provider-initiated testing makes ART available to individuals less motivated to seek care, patients may need additional adherence support, especially addressing uncertainty about the health benefits of ART.

Abstract Background Antiretroviral therapy (ART) has dramatically reduced morbidity and mortality among people with HIV infection; however, mortality after the start of ART is high in resource-limited settings. We investigated risk factors for mortality among adults starting ART in a multi-clinic community programme in South Africa. Methods Cohort of adults starting ART at 27 clinics between February 2005 and June 2006, followed to 31st March 2007. Kaplan-Meier survival estimates were used to describe overall mortality. Shared frailty Cox regression was used to identify baseline risk factors for early mortality. Results Among 1350 participants (median age 35.5 years, 60% female, median CD4 count 83/μL [interquartile range (27 - 147)], median follow-up 13.4 months), there were 185 deaths, overall mortality rate 13/100 pyrs; for 0-3, 3-9 and >9 months from ART start mortality rates were 24, 13 and 6/100 pyrs respectively. 43% of the deaths were in the first 3 months of treatment. Risk factors for mortality in univariable analysis were baseline CD4 count, viral load, haemoglobin and body mass index, in multivariable analysis adjusting for age and gender, only CD4 count and haemoglobin remained independently associated with proportional hazards not being satisfied for haemoglobin. Adjusted hazard ratios (aHR) for participants with haemoglobin 11.9(f)/12.9 (m) g/mL were 4.99, 3.05 and 0.12 respectively comparing to 10-11.9 (f)/12.9 (m)g/mL in the first 3 months of ART. aHRs for CD4 counts were 0.40, 0.38 and 0.34 for 50-99, 100-200 and >200/μL comparing to Conclusions The high mortality rate in the first 3 months underlines the need for earlier HIV diagnosis so that ART can be initiated earlier. Low haemoglobin and low CD4 count are both strong predictors of mortality, and could be used to identify individuals at high risk who might benefit from intensive case management.

Abstract Background Reasons for the variation in reported treatment outcomes from antiretroviral therapy (ART) programmes in developing countries are not clearly defined. Methods Among ART-naïve individuals in a workplace ART programme in South Africa we determined virological outcomes at 12 months, and risk factors for suboptimal virological outcome, defined as plasma HIV-1 viral load >= 400 copies/ml. Results Among 1760 individuals starting ART before July 2004, 1172 were in follow-up at 12 months of whom 953 (81%) had a viral load measurement (median age 41 yrs, 96% male, median baseline CD4 count 156 × 106/l). 71% (681/953) had viral load < 400 copies/ml at 12 months. In a multivariable analysis, independent predictors of suboptimal virological outcome at 12 months were 100,000 compared to = 1 log decrease in viral load. Conclusion Virological response at six weeks after ART start was the strongest predictor of suboptimal virological outcome at 12 months, and may identify individuals who need interventions such as additional adherence support. Self reported adherence was less strongly associated but identified different patients compared with viral load at 6 weeks. Site of delivery had an important influence on virological outcomes; factors at the health system level which influence outcome need further investigation to guide development of effective ART programmes.

Abstract Background As ART programmes in African settings expand beyond the pilot stages, adherence to treatment may become an increasing challenge. This qualitative study examines potential barriers to, and facilitators of, adherence to ART in a workplace programme in South Africa. Methods We conducted key informant interviews with 12 participants: six ART patients, five health service providers (HSPs) and one human resources manager. Results The main reported barriers were denial of existence of HIV or of one's own positive status, use of traditional medicines, speaking a different language from the HSP, alcohol use, being away from home, perceived severity of side-effects, feeling better on treatment and long waiting times at the clinic. The key facilitators were social support, belief in the value of treatment, belief in the importance of one's own life to the survival of one's family, and the ability to fit ART into daily life schedules. Conclusion Given the reported uncertainty about the existence of HIV disease and the use of traditional medicines while on ART, despite a programme emphasising ART counselling, there is a need to find effective ways to support adherence to ART even if the individual does not accept biomedical concepts of HIV disease or decides to use traditional medicines. Additionally, providers should identify ways to minimize barriers in communication with patients with whom they have no common language. Finally, dissatisfaction with clinical services, due to long waiting times, should be addressed.

Information theoretic properties of flat fading channels with multiple antennas are investigated. Perfect channel knowledge at the receiver is assumed. Expressions for maximum information rates and outage probabilities are derived. The advantages of transmitter channel knowledge are determined and a critical threshold is found beyond which such channel knowledge gains very little. Asymptotic expressions for the error exponent are found. For the case of transmit diversity closed form expressions for the error exponent and cutoff rate are given. The use of orthogonal modulating signals is shown to be asymptotically optimal in terms of information rate.