A comprehensive guide to MEGA-PRESS for GABA measurement.

The aim of this guideline is to provide a series of evidence-based recommendations that allow those new to using MEGA-PRESS to produce high-quality data for the measurement of GABA levels using edited magnetic resonance spectroscopy with the MEGA-PRESS sequence at 3T. GABA is the main inhibitory neurotransmitter of the central nervous system and has been increasingly studied due to its relevance in many clinical disorders of the central nervous system. MEGA-PRESS is the most widely used method for quantification of GABA at 3T, but is technically challenging and operates at a low signal-to-noise ratio. Therefore, the acquisition of high-quality MRS data relies on avoiding numerous pitfalls and observing important caveats. The guideline was developed by a working party that consisted of experts in MRS and experts in guideline development and implementation, together with key stakeholders. Strictly following a translational framework, we first identified evidence using a systematically conducted scoping literature review, then synthesized and graded the quality of evidence that formed recommendations. These recommendations were then sent to a panel of 21 world leaders in MRS for feedback and approval using a modified-Delphi process across two rounds. The final guideline consists of 23 recommendations across six domains essential for GABA MRS acquisition (Parameters, Practicalities, Data acquisition, Confounders, Quality/reporting, Post-processing). Overall, 78% of recommendations were formed from high-quality evidence, and 91% received agreement from over 80% of the expert panel. These 23 expert-reviewed recommendations and accompanying extended documentation form a readily useable guideline to allow those new to using MEGA-PRESS to design appropriate MEGA-PRESS study protocols and generate high-quality data.

Assessment of a compounded synthetic adrenocorticotropic hormone product in 17 healthy dogs.

OBJECTIVES: Synthetic adrenocorticotropic hormone or tetracosactide is routinely used in the diagnosis of hypoadrenocorticism and frequently in the diagnosis and treatment of hyperadrenocorticism. There have been repeated shortages of tetracosactide in recent years in Australia. This study investigated the agreement of serum cortisol after a compounded tetracosactide (Bova Aus), compared to commercial tetracosactide (Synacthen®) in healthy dogs. METHODS: Prospective crossover study using 20 dogs. Ten dogs received 5 µg/kg Synacthen® on day 1 and 5 µg/kg compounded tetracosactide on Day 2. The other 10 dogs received the reverse order. Cortisol concentrations in each dog 1 h after injection were compared for agreement, which was defined as the limits of agreement of the Bland-Altman ratio to be within a range of 0.8-1.25. Passing-Bablok regression analysis examined for constant and proportional biases. RESULTS: Three dogs were excluded with post-stimulation serum cortisol concentrations markedly outside reference interval. For the remaining 17 dogs, Bland-Altman ratio analysis of cortisol concentration (tetracosactide/Synacthen®) at 1 h found virtually no constant bias (mean of ratios 1.01;95% CI 0.97-1.05) and 95% limits of agreement were 0.88 (95% CI 0.78-0.90) and 1.17 (95% CI 1.13-1.25). This met our criteria for agreement between cortisol concentrations. Bias of the Bland-Altman difference was 2.8 nmol/L (95% CI -7.2 to 12.8); 95% limits of agreement -35.2 nmol/L (95% CI -57.0 to -26.1) and 40.8 nmol/L (95% CI 31.7-62.6). Passing-Bablok regression analysis did not identify bias. CONCLUSION: In healthy dogs, cortisol concentrations were in agreement after compounded tetracosactide compared to commercial tetracosactide, Synacthen®.

Diel Periodicity in Males of the Navel Orangeworm (Lepidoptera: Pyralidae) as Revealed by Automated Camera Traps.

Navel orangeworm, Amyelois transitella (Walker), is a key pest of walnuts, pistachio, and almonds in California. Pheromone mating disruption using timed aerosol dispensers is an increasingly common management technique. Dispenser efficiency may be increased by timing releases with the active mating period of navel orangeworm. Past work found that the peak time of sexual activity for navel orangeworm females is 2 h before sunrise when temperatures are above 18°C. Inference of male responsiveness from data collected in that study was limited by the necessity of using laboratory-reared females as a source of sex pheromone emission to attract males and the inherent limitations of human observers for nocturnal events. Here we used camera traps baited with artificial pheromone to observe male navel orangeworm mating response in the field over two field seasons. Male response to synthetic pheromone exhibited diel patterns broadly similar to females, i.e., they were active for a brief period of 2-3 h before dawn under summer conditions and began responding to pheromone earlier and over a longer period of time during spring and fall. But contrary to the previous findings with females, some males were captured at all hours of the day and night, and there was no evidence of short-term change of pheromone responsiveness in response to temperature. Environmental effects on the response of navel orangeworm males to an artificial pheromone source differ in important ways from the environmental effects on female release of sex pheromone.

An improved set of electron-THFA cross sections refined through a neural network-based analysis of swarm data.

We review experimental and theoretical cross sections for electron transport in α-tetrahydrofurfuryl alcohol (THFA) and, in doing so, propose a plausible complete set. To assess the accuracy and self-consistency of our proposed set, we use the pulsed-Townsend technique to measure drift velocities, longitudinal diffusion coefficients, and effective Townsend first ionization coefficients for electron swarms in admixtures of THFA in argon, across a range of density-reduced electric fields from 1 to 450 Td. These measurements are then compared to simulated values derived from our proposed set using a multi-term solution of Boltzmann's equation. We observe discrepancies between the simulation and experiment, which we attempt to address by employing a neural network model that is trained to solve the inverse swarm problem of unfolding the cross sections underpinning our experimental swarm measurements. What results from our neural network-based analysis is a refined set of electron-THFA cross sections, which we confirm is of higher consistency with our swarm measurements than that which we initially proposed. We also use our database to calculate electron transport coefficients in pure THFA across a range of reduced electric fields from 0.001 to 10 000 Td.

Quantitative MRI: Defining repeatability, reproducibility and accuracy for prostate cancer imaging biomarker development.

INTRODUCTION: Quantitative MRI (qMRI) parameters have been increasingly used to develop predictive models to accurately monitor treatment response in prostate cancer after radiotherapy. To reliably detect changes in signal due to treatment response, predictive models require qMRI parameters with high repeatability and reproducibility. The purpose of this study was to measure qMRI parameter uncertainties in both commercial and in-house developed phantoms to guide the development of robust predictive models for monitoring treatment response. MATERIALS AND METHODS: ADC, T1, and R2* values were acquired across three 3 T scanners with a prostate-specific qMRI protocol using the NIST/ISMRM system phantom, RSNA/NIST diffusion phantom, and an in-house phantom. A B1 field map was acquired to correct for flip angle inhomogeneity in T1 maps. All sequences were repeated in each scan to assess within-session repeatability. Weekly scans were acquired on one scanner for three months with the in-house phantom. Between-session repeatability was measured with test-retest scans 6-months apart on all scanners with all phantoms. Accuracy, defined as percentage deviation from reference value for ADC and T1, was evaluated using the system and diffusion phantoms. Repeatability and reproducibility coefficients of variation (%CV) were calculated for all qMRI parameters on all phantoms. RESULTS: Overall, repeatability CV of ADC was <2.40%, reproducibility CV was <3.98%, and accuracy ranged between -8.0% to 2.7% across all scanners. Applying B1 correction on T1 measurements significantly improved the repeatability and reproducibility (p<0.05) but increased error in accuracy (p<0.001). Repeatability and reproducibility of R2* was <4.5% and <7.3% respectively in the system phantom across all scanners. CONCLUSION: Repeatability, reproducibility, and accuracy in qMRI parameters from a prostate-specific protocol was estimated using both commercial and in-house phantoms. Results from this work will be used to identify robust qMRI parameters for use in the development of predictive models to longitudinally monitor treatment response for prostate cancer in current and future clinical trials.

Human papillomavirus and cervical cancer risk perception and vaccine acceptability among adolescent girls and young women in Durban, South Africa.

BACKGROUND: The relationship between HIV and cervical cancer is well established. Interventions that focus on creating human papillomavirus (HPV) vaccine and cervical cancer prevention messaging for adolescents, caregivers and educators will increase uptake of HPV vaccinations, HPV testing and cervical cancer screening for high-risk adolescent girls and young women (AGYW). In order to effectively develop appropriate interventions, it is important to examine AGYW's perceptions regarding their personal risk of acquiring HPV, as well as vaccine acceptability. OBJECTIVES: To measure the level of perceived personal risk of acquiring HPV and developing cervical cancer; examine the sociodemographic and behavioural factors associated with perceived risk; and assess HPV vaccine acceptability. METHODS: AGYW aged 16 - 24 years participating in the AYAZAZI study in Durban, South Africa (SA), were invited to participate in the AYA-HPV Prevention Project (AHPP), and were administered a questionnaire that assessed HPV, cervical cancer and vaccine awareness and knowledge, self-perceived HPV and cervical cancer risk, HPV vaccine uptake and acceptability, and participation in cervical cancer screening. The questionnaire measured self-perceived risk of acquiring HPV and developing cervical cancer for the respondent and other young women, as well as vaccine acceptability. Data from the main AYAZAZI study (12-month) visit were linked to AHPP substudy data. Descriptive statistics were used to analyse sociodemographic variables at the 12-month time point. Self-perceived HIV, HPV and cervical cancer risk was measured using an ordinal scale. Chi-square analyses were used to examine differences in sociodemographic and behavioural factors according to self-perceived risk of HPV and cervical cancer. RESULTS: Only a small portion of participants (14.3%) had heard of HPV. Overall, 43.0% (n=49) perceived themselves as at low HPV risk. There were significant differences in self-perceived risk of cervical cancer by age group, income and pregnancy status. The highest proportion of AGYW who perceived themselves as at high risk of cervical cancer reported being sexually active (p=0.002). Although many participants reported not knowing about HPV prior to the study, after learning about it during the study, most said that they would be willing to receive the vaccine (97.5%). CONCLUSIONS: Most young women in SA do not have access to the national HPV vaccine programme, as only girls in grade 4 in some public schools qualify. Almost all participants indicated that if the vaccine was free and recommended by a healthcare professional, they would accept it. Availability of the HPV vaccine and timely treatment of HPV infections are key issues to address in efforts to decrease cervical cancer worldwide.

The architecture of the Gram-positive bacterial cell wall.

The primary structural component of the bacterial cell wall is peptidoglycan, which is essential for viability and the synthesis of which is the target for crucial antibiotics1,2. Peptidoglycan is a single macromolecule made of glycan chains crosslinked by peptide side branches that surrounds the cell, acting as a constraint to internal turgor1,3. In Gram-positive bacteria, peptidoglycan is tens of nanometres thick, generally portrayed as a homogeneous structure that provides mechanical strength4-6. Here we applied atomic force microscopy7-12 to interrogate the morphologically distinct Staphylococcus aureus and Bacillus subtilis species, using live cells and purified peptidoglycan. The mature surface of live cells is characterized by a landscape of large (up to 60 nm in diameter), deep (up to 23 nm) pores constituting a disordered gel of peptidoglycan. The inner peptidoglycan surface, consisting of more nascent material, is much denser, with glycan strand spacing typically less than 7 nm. The inner surface architecture is location dependent; the cylinder of B. subtilis has dense circumferential orientation, while in S. aureus and division septa for both species, peptidoglycan is dense but randomly oriented. Revealing the molecular architecture of the cell envelope frames our understanding of its mechanical properties and role as the environmental interface13,14, providing information complementary to traditional structural biology approaches.

Profiling of how nociceptor neurons detect danger - new and old foes.

The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro-immune interplay is still ill-defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH 1-mediated immunity but also as drivers of TH 2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide-ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

Regulation of the ß-Adrenergic Receptor Signaling Pathway in Sustained Ligand-Activated Preconditioning.

Sustained ligand-activated preconditioning (SLP), induced with chronic opioid receptor (OR) agonism, enhances tolerance to ischemia/reperfusion injury in young and aged hearts. Underlying mechanisms remain ill-defined, although early data implicate phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) during the induction phase, and ß 2-adrenoceptor (ß 2-AR), Gs alpha subunit (Gα s), and protein kinase A (PKA) involvement in subsequent cardioprotection. Here, we tested for induction of a protective ß 2-AR/Gα s/PKA signaling axis with SLP to ascertain whether signaling changes were PI3K-dependent (by sustained cotreatment with wortmannin), and whether the downstream PKA target Rho kinase (ROCK) participates in subsequent cardioprotection (by acute treatment with fasudil). A protected phenotype was evident after 5 days of OR agonism (using morphine) in association with increased membrane versus reduced cytosolic levels of total and phosphorylated ß 2-ARs; increased membrane and cytosolic expression of 52 and 46 kDa Gα s isoforms, respectively; and increased phosphorylation of PKA and Akt. Nonetheless, functional sensitivities of ß 2-ARs and adenylyl cyclase were unchanged based on concentration-response analyses for formoterol, fenoterol, and 6-[3-(dimethylamino)propionyl]-forskolin. Protection with SLP was not modified by ROCK inhibition, and changes in ß 2-AR, Gα s, and PKA expression appeared insensitive to PI3K inhibition, although 5 days of wortmannin alone exerted unexpected effects on signaling (also increasing membrane ß 2-AR and PKA expression/phosphorylation and Gα s levels). In summary, sustained OR agonism upregulates cardiac membrane ß 2-AR expression and phosphorylation in association with increased Gα s subtype levels and PKA phosphorylation. While Akt phosphorylation was evident, PI3K activity appears nonessential to OR upregulation of the ß 2-AR signal axis. This opioidergic remodeling of ß 2-AR signaling may explain ß 2-AR, Gα s, and PKA dependence of SLP protection.

Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Children of preschool age often have episodes of virus-associated wheeze, and research assessing efficacy of corticosteroids for paediatric wheeze exacerbations is inconclusive. METHODS: This non-inferiority, randomised, double-blind, placebo-controlled trial was to compare the efficacy of placebo versus oral prednisolone in children aged 24-72 months presenting with virus-associated wheeze at the paediatric emergency department of Princess Margaret Hospital in Perth, WA, Australia. Eligible participants were randomly assigned (1:1) using a computer-generated random number program to receive placebo or prednisolone (1 mg/kg per day) for 3 days. The primary outcome was total length of stay in hospital until ready for discharge. Following an analysis to test the hypothesis that placebo is non-inferior to prednisolone, a post-hoc superiority analysis was done to test the hypothesis that prednisolone was superior to placebo. A non-inferiority margin of 10% was used to establish non-inferiority. Efficacy analyses were on a modified intention-to-treat basis, whereby patients were excluded from the final efficacy analysis if consent was withdrawn, two doses of study drug were vomited, or paperwork was lost. All participants were included in safety analyses. This study is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12612000394842. FINDINGS: Between June 11, 2012, and June 10, 2015, we screened 3727 patients for eligibility. 624 eligible patients were randomly assigned to treatment, and 605 patients were included in the modified intention-to-treat analysis (300 patients from the placebo group, 305 patients from the prednisolone group). The median length of stay until ready for discharge was longer in the placebo group (540 min [IQR 124-971]) than in the prednisolone group (370 min [121-709]); placebo was inferior to prednisolone. In the post-hoc superiority analysis of 605 patients, the unadjusted ratio of geometric mean for length of stay was 0·79 (95% CI 0·64-0·97; p=0·0227) for the prednisolone group relative to the placebo group. No serious adverse events were reported during the study or follow-up period. One child in the placebo group had a non-specific maculopapular rash, which resolved spontaneously. Two children (one from each group) were reported to be hyperactive during follow-up assessments. INTERPRETATION: Oral prednisolone had a clear benefit over placebo at reducing the length of stay in children presenting to a paediatric emergency department with virus-associated wheeze and was well tolerated. FUNDING: Western Australian Department of Health.

New insights into the correlation structure of DSM-IV depression symptoms in the general population v. subsamples of depressed individuals.

AIMS: Previous research failed to uncover a replicable dimensional structure underlying the symptoms of depression. We aimed to examine two neglected methodological issues in this research: (a) adjusting symptom correlations for overall depression severity; and (b) analysing general population samples v. subsamples of currently depressed individuals. METHODS: Using population-based cross-sectional and longitudinal data from two nations (Switzerland, 5883 young men; USA, 2174 young men and 2244 young women) we assessed the dimensions of the nine DSM-IV depression symptoms in young adults. In each general-population sample and each subsample of currently depressed participants, we conducted a standardised process of three analytical steps, based on exploratory and confirmatory factor and bifactor analysis, to reveal any replicable dimensional structure underlying symptom correlations while controlling for overall depression severity. RESULTS: We found no evidence of a replicable dimensional structure across samples when adjusting symptom correlations for overall depression severity. In the general-population samples, symptoms correlated strongly and a single dimension of depression severity was revealed. Among depressed participants, symptom correlations were surprisingly weak and no replicable dimensions were identified, regardless of severity-adjustment. CONCLUSIONS: First, caution is warranted when considering studies assessing dimensions of depression because general population-based studies and studies of depressed individuals generate different data that can lead to different conclusions. This problem likely generalises to other models based on the symptoms' inter-relationships such as network models. Second, whereas the overall severity aligns individuals on a continuum of disorder intensity that allows non-affected individuals to be distinguished from affected individuals, the clinical evaluation and treatment of depressed individuals should focus directly on each individual's symptom profile.

Brain functional connectome abnormalities in amyotrophic lateral sclerosis are associated with disability and cortical hyperexcitability.

BACKGROUND AND PURPOSE: The present study utilized a multimodal approach encompassing connectome networks combined with brain volume analysis, and assessment of cortical excitability to provide novel insights into amyotrophic lateral sclerosis (ALS) pathogenesis. METHODS: Magnetic resonance images were acquired using a 3.0-Tesla Signa HDx scanner (GE Healthcare, Milwaukee, WI, USA), using an eight-channel head coil. Magnetic resonance images for the resting-state scan were acquired using an echo-planar imaging magnetic resonance sequence, acquiring 40 contiguous axial/oblique slices. Structural magnetic resonance imaging three-dimensional T1-weighted images were acquired in the sagittal plane using three-dimensional spoiled gradient echo sequences. For structural imaging, a T1-weighted high-resolution (3.0-Tesla) magnetic resonance imaging scan was used. Cortical excitability was assessed by using the threshold-tracking transcranial magnetic stimulation paradigm. Network-based statistics and whole-brain functional topology (using graph theoretical approaches) assessed functional connectivity. RESULTS: Using a global network-based statistical analysis approach, functional connectivity was increased in 12 network edges connecting 14 nodes (P < 0.05) within the frontal, temporal, parietal and subcortical regions. Analysis of local connectedness disclosed dichotomous effects with reduced connectivity in frontal regions and increased connectivity in occipital regions in ALS. Cortical hyperexcitability was evident in patients with ALS, negatively correlated with functional connectivity changes in the pre-central gyrus (P < 0.01). Connectivity changes in the frontal regions were negatively associated with functional disability (P < 0.05). CONCLUSIONS: Multimodal assessment of cortical function in patients with ALS identified deficits in functional connectivity associated with cortical hyperexcitability that correlated with patient disability. Novel integration of functional brain assessment further contributes to the understanding of disease pathogenesis in ALS.

Geospatial analysis of household spread of Ebola virus in a quarantined village - Sierra Leone, 2014.

We performed a spatial-temporal analysis to assess household risk factors for Ebola virus disease (Ebola) in a remote, severely-affected village. We defined a household as a family's shared living space and a case-household as a household with at least one resident who became a suspect, probable, or confirmed Ebola case from 1 August 2014 to 10 October 2014. We used Geographic Information System (GIS) software to calculate inter-household distances, performed space-time cluster analyses, and developed Generalized Estimating Equations (GEE). Village X consisted of 64 households; 42% of households became case-households over the observation period. Two significant space-time clusters occurred among households in the village; temporal effects outweighed spatial effects. GEE demonstrated that the odds of becoming a case-household increased by 4·0% for each additional person per household (P < 0·02) and 2·6% per day (P < 0·07). An increasing number of persons per household, and to a lesser extent, the passage of time after onset of the outbreak were risk factors for household Ebola acquisition, emphasizing the importance of prompt public health interventions that prioritize the most populated households. Using GIS with GEE can reveal complex spatial-temporal risk factors, which can inform prioritization of response activities in future outbreaks.

Chemical, biological, and DNA markers for tracing slaughterhouse effluent.

Agricultural practices, if not managed correctly, can have a negative impact on receiving environments via waste disposal and discharge. In this study, a chicken slaughter facility on the rural outskirts of Sydney, Australia, has been identified as a possible source of persistent effluent discharge into a peri-urban catchment. Questions surrounding the facility's environmental management practices go back more than four decades. Despite there having never been a definitive determination of the facility's impact on local stream water quality, the New South Wales Environment Protection Authority (NSW EPA) has implemented numerous pollution reduction requirements to manage noise and water pollution at the slaughter facility. However, assessment of compliance remains complicated by potential additional sources of pollution in the catchment. To unravel this long-standing conundrum related to water pollution we apply a forensic, multiple lines of evidence approach to delineate the origin of the likely pollution source(s). Water samples collected between 2014 and 2016 from irrigation pipes and a watercourse exiting the slaughter facility had elevated concentrations of ammonia (max: 63,000µg/L), nitrogen (max: 67,000µg/L) and phosphorus (max: 39,000µg/L), which were significantly higher than samples from adjacent streams that did not receive direct runoff from the facility. Arsenic, sometimes utilised in growth promoting compounds, was detected in water discharging from the facility up to ~4 times (max 3.84µg/L) local background values (<0.5µg/L), with inorganic As(∑V+III) being the dominant species. The spatial association of elevated water pollution to the facility could not unequivocally distinguish a source and consequently DNA analysis of a suspected pollution discharge event was undertaken. Analysis of catchment runoff from several local streams showed that only water sampled at the downstream boundary of the facility tested positive for chicken DNA, with traces of duck DNA being absent, which was a potential confounder given that wild ducks are present in the area. Further, PCR analysis showed that only the discharge water emanating from the slaughter facility tested positive for a generalized marker of anthropogenic pollution, the clinical class 1 integron-integrase gene. The environmental data collected over a three-year period demonstrates that the slaughter facility is indisputably the primary source of water-borne pollution in the catchment. Moreover, application of DNA and PCR for confirming pollution sources demonstrates its potential for application by regulators in fingerprinting pollution sources.

Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism.

Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality.

The caregiver burden in lupus: findings from UNVEIL, a national online lupus survey in the United States.

OBJECTIVES: Lupus imposes a substantial burden on patients; however, little is known about its impact on those caring for patients with the disease. In this study, we examined the impact 'caring for patients with lupus' has on caregivers from their own perspective. METHODS: UNVEIL was a one-time online national cross-sectional survey developed in partnership with the Lupus Foundation of America and fielded targeting the US Lupus Foundation of America constituents in 2014. Eligible caregivers were adults who self-identified as unpaid caregivers of patients with lupus. Eligible caregivers had to complete a series of sociodemographic questions as well as a series of well established outcome measures, such as the Short Form 12v2 Health Survey, the Work Productivity and Activity Index, the Caregiver Burden Inventory, and the Perceived Benefits of Caregiving Scale. RESULTS: A total of 253 caregivers completed the survey. The majority of caregivers (90.1%) were aged 60 years or younger, more than half (54.2%) were men, and more than half (59.7%) identified themselves as either a spouse or a partner to the patient with lupus they were caring for. Overall health-related quality of life was close to the norm mean of the general US population. Caregivers who were employed missed an average of 12.8% of paid work time due to caregiving responsibilities and reported a 33.5% reduction in on-the-job effectiveness. Nearly half of the caregivers surveyed (49.4%) indicated that their caregiving responsibilities impacted their ability to socialize with friends, and almost all caregivers (97.6%) reported experiencing increased anxiety and stress in relation to their caregiving role. CONCLUSIONS: Caregiving for patients with lupus has a substantial impact on the work productivity and the social and emotional functioning of caregivers. Healthcare professionals and policymakers should continually assess the impact of healthcare decisions on the well-being of those caring for patients with lupus.

Hydrogeological typologies of the Indo-Gangetic basin alluvial aquifer, South Asia.

The Indo-Gangetic aquifer is one of the world's most important transboundary water resources, and the most heavily exploited aquifer in the world. To better understand the aquifer system, typologies have been characterized for the aquifer, which integrate existing datasets across the Indo-Gangetic catchment basin at a transboundary scale for the first time, and provide an alternative conceptualization of this aquifer system. Traditionally considered and mapped as a single homogenous aquifer of comparable aquifer properties and groundwater resource at a transboundary scale, the typologies illuminate significant spatial differences in recharge, permeability, storage, and groundwater chemistry across the aquifer system at this transboundary scale. These changes are shown to be systematic, concurrent with large-scale changes in sedimentology of the Pleistocene and Holocene alluvial aquifer, climate, and recent irrigation practices. Seven typologies of the aquifer are presented, each having a distinct set of challenges and opportunities for groundwater development and a different resilience to abstraction and climate change. The seven typologies are: (1) the piedmont margin, (2) the Upper Indus and Upper-Mid Ganges, (3) the Lower Ganges and Mid Brahmaputra, (4) the fluvially influenced deltaic area of the Bengal Basin, (5) the Middle Indus and Upper Ganges, (6) the Lower Indus, and (7) the marine-influenced deltaic areas.

L'aquifère de l'Indus et du Gange est une des ressources en eau transfrontalière la plus importante au monde et un des aquifères le plus exploité au monde. Pour mieux comprendre le système aquifère, des typologies ont été caractérisées pour cet aquifère ; elles intègrent pour la première fois un jeu de données disponibles sur l'ensemble du bassin de l'Indus et du Gange à une échelle transfrontalière, et apportent une conceptualisation alternative de ce système aquifère. Traditionnellement considéré et cartographié comme un simple aquifère homogène aux propriétés aquifères similaires et comme une ressource d'eau souterraine à l'échelle transfrontalière, les typologies mettent en évidence des différences significatives spatiales de la recharge, de la perméabilité, de la capacité de stockage et de la chimie des eaux souterraines sur l'ensemble du système aquifère à une échelle transfrontalière. Ces changements sont systématiques coïncidant aux changements à large échelle de la sédimentologie de l'aquifère alluvial du Pléistocène et de l'Holocène, du climat et des pratiques récentes d'irrigation. Sept typologies de l'aquifère sont présentées, chacune ayant un ensemble distinct de défis et d'opportunités pour le développement des eaux souterraines et une résilience différente à l'exploitation et au changement climatique. Les sept typologies sont: (1) la marge de piedmont, (2) Le haut Indus et le Ganges moyen supérieur, (3) le Ganges inférieur et le Brahmapoutre moyen, (4) la zone deltaïque du bassin du Bengale sous influence fluviale, (5) l'Indus moyen et le Ganges supérieur, (6) l'Indus inférieur, et (7) la zone deltaïque sous influence marine.

El acuífero Indo-Gangético es uno de los recursos hídricos transfronterizos más importantes y el acuífero más explotado del mundo. Para comprender mejor el sistema acuífero, por primera vez se han caracterizado tipologías para el acuífero, integrando los conjuntos de datos existentes a través de la cuenca hidrográfica Indo-Ganges a una escala transfronteriza, y proporcionando una conceptualización alternativa de este sistema acuífero. Tradicionalmente consideradas y cartografiadas como un solo acuífero homogéneo de propiedades acuíferas y recursos de agua subterránea comparables a escala transfronteriza, las tipologías iluminan diferencias espaciales significativas en la recarga, permeabilidad, almacenamiento y química del agua subterránea a través del sistema acuífero a esta escala transfronteriza. Estos cambios son mostrados por ser sistemáticos, coincidentes con cambios en gran escala en la sedimentología del acuífero aluvial del Pleistoceno y del Holoceno, en el clima y en las prácticas recientes de riego. Se presentan siete tipologías del acuífero, cada una con un conjunto distinto de desafíos y oportunidades para el desarrollo del agua subterránea y una diferente resiliencia a la extracción y al cambio climático. Las siete tipologías son: (1) el margen del piedemonte, (2) el Indus superior y el Ganges superior-medio, (3) el Ganges inferior y el Brahmaputra medio, (4) el área deltaica fluvialmente influenciada de la cuenca de Bengala, (5) el Ganges superior, (6) el Indo Inferior, y (7) las áreas deltaicas con influencia marina.

O aquífero do Indo-Gangético é um dos recursos hídricos transfronteiriços mais importantes do mundo, e o mais explorado. Para melhor entender o sistema aquífero, tipologias foram caracterizadas para o aquífero, que integram pela primeira vez bancos de dados existentes sobre a bacia de abastecimento Indo-Gangética em uma escala transfornteiriça, e fornecem uma conceptualização alternativa desse sistema aquífero. Tradicionalmente considerado e mapeado como um aquífero homogêneo de propriedades aquíferas comparáveis e recursos subterrâneos em escala transfronteiriça, as tipologias elucidam diferenças espaciais significantes na recarga, permeabilidade, armazenamento, e química das águas subterrâneas pelo aquífero nessa escala transfronteiriça. Essas mudanças aparentam ser sistemáticas, concorrentes com mudanças em larga escala na sedimentologia do aquífero aluvial do Pleistoceno e Holoceno, clima e práticas recentes de irrigação. Sete tipologias do aquífero são apresentadas, cada uma tendo conjuntos de desafios e oportunidades distintos para o desenvolvimento das águas subterrâneas e uma resiliência diferente nas mudanças de extração e clima. As sete tipologias são: (1) a margem piemonte, (2) O Alto Indo e o Alto-médio Ganges, (3) O Baixo Ganges e o Médio Brahmaputra, (4) a área deltaica influenciada fluvialmente da Bacia de Bengala, (5) o Médio Indo e o Alto Ganges, (6) o Baixo Indo, e (7) as áreas deltaicas com influencia marinha.