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Background and ObjectivesMotor speech function, including speech timing, is a key domain for diagnosing nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments use subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically confirmed diagnoses. This study overcomes such caveats using automated speech timing analyses in a unique cohort of autopsy-proven cases.MethodsIn a cross-sectional study, we administered an overt reading task and quantified articulation rate, mean syllable and pause duration, and syllable and pause duration variability. Neuroanatomical disruptions were assessed using cortical thickness and white matter (WM) atrophy analysis.ResultsWe evaluated 22 persons with nfvPPA (mean age: 67.3 years; 13 female patients) and confirmed underlying 4-repeat tauopathy, 15 persons with semantic variant primary progressive aphasia (svPPA; mean age: 66.5 years; 8 female patients), and 10 healthy controls (HCs; 70 years; 5 female patients). All 5 speech timing measures revealed alterations in persons with nfvPPA relative to both the HC and svPPA groups, controlling for dementia severity. The articulation rate robustly discriminated individuals with nfvPPA from HCs (area under the ROC curve [AUC] = 0.95), outperforming specialist-dependent perceptual measures of dysarthria and apraxia of speech severity. Patients with nfvPPA exhibited structural abnormalities in left precentral and middle frontal as well as bilateral superior frontal regions, including their underlying WM. The articulation rate correlated with atrophy of the left pars opercularis and supplementary/presupplementary motor areas. Secondary analyses showed that, controlling for dementia severity, all measures yielded greater deficits in patients with nfvPPA and corticobasal degeneration (nfvPPA-CBD, n = 12) than in those with progressive supranuclear palsy pathology (nfvPPA-PSP, n = 10). The articulation rate robustly discriminated between individuals in each subgroup (AUC = 0.82). More widespread cortical thinning was observed for the nfvPPA-CBD than the nfvPPA-PSP group across frontal regions.DiscussionAutomated speech timing analyses can capture specific markers of nfvPPA while potentially discriminating between patients with different tauopathies. Thanks to its objectivity and scalability; this approach could support standard speech assessments.Classification of EvidenceThis study provides Class III evidence that automated speech analysis can accurately differentiate patients with nonfluent PPA from normal controls and patients with semantic variant PPA.

IntroductionRemote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).MethodsA diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD=0 [N=101]; prodromal: 0.5 [N=49]; symptomatic ≥1 [N=51]; not measured [N=13]) were asked to complete ALLFTD-mApp tests on their smartphone three times within 12 days. They completed smartphone familiarity and participation experience surveys.ResultsIt was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity was associated with poorer performance across several tests.DiscussionThese findings suggest that the ALLFTD-mApp study protocol is feasible and acceptable for remote FTD research.HighlightsThe ALLFTD Mobile App is a smartphone-based platform for remote, self-administered data collection.The ALLFTD Mobile App consists of a comprehensive battery of surveys and tests of executive functioning, memory, speech and language, and motor abilities.Remote digital data collection using the ALLFTD Mobile App was feasible in a multicenter research consortium that studies FTD. Data was collected in healthy controls and participants with a range of diagnoses, particularly FTD spectrum disorders.Remote digital data collection was well accepted by participants with a variety of diagnoses.

Semantic variant primary progressive aphasia is a clinical syndrome characterized by marked semantic deficits, anterior temporal lobe atrophy and reduced connectivity within a distributed set of regions belonging to the functional network associated with semantic processing. However, to fully depict the clinical signature of semantic variant primary progressive aphasia, it is necessary to also characterize preserved neural networks and linguistic abilities, such as those subserving speech production. In this case-control observational study, we employed whole-brain seed-based connectivity on task-free MRI data of 32 semantic variant primary progressive aphasia patients and 46 healthy controls to investigate the functional connectivity of the speech production network and its relationship with the underlying grey matter. We investigated brain-behaviour correlations with speech fluency measures collected through clinical tests (verbal agility) and connected speech (speech rate and articulation rate). As a control network, we also investigated functional connectivity within the affected semantic network. Patients presented with increased connectivity in the speech production network between left inferior frontal and supramarginal regions, independent of underlying grey matter volume. In semantic variant primary progressive aphasia patients, preserved (verbal agility) and increased (articulation rate) speech fluency measures correlated with increased connectivity between inferior frontal and supramarginal regions. As expected, patients demonstrated decreased functional connectivity in the semantic network (dependent on the underlying grey matter atrophy) associated with average nouns' age of acquisition during connected speech. Collectively, these results provide a compelling model for studying compensation mechanisms in response to disease that might inform the design of future rehabilitation strategies in semantic variant primary progressive aphasia.

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The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false-negative viral PCR test results. Such tests are also susceptible to false-positive results due to trace contamination from high viral titer samples. Host immune response markers provide an orthogonal indication of infection that can mitigate these concerns when combined with direct viral detection. Here, we leverage nasopharyngeal swab RNA-seq data from patients with COVID-19, other viral acute respiratory illnesses, and nonviral conditions (n = 318) to develop support vector machine classifiers that rely on a parsimonious 2-gene host signature to diagnose COVID-19. We find that optimal classifiers include an interferon-stimulated gene that is strongly induced in COVID-19 compared with nonviral conditions, such as IFI6, and a second immune-response gene that is more strongly induced in other viral infections, such as GBP5. The IFI6+GBP5 classifier achieves an area under the receiver operating characteristic curve (AUC) greater than 0.9 when evaluated on an independent RNA-seq cohort (n = 553). We further provide proof-of-concept demonstration that the classifier can be implemented in a clinically relevant RT-qPCR assay. Finally, we show that its performance is robust across common SARS-CoV-2 variants and is unaffected by cross-contamination, demonstrating its utility for improved accuracy of COVID-19 diagnostics. IMPORTANCE In this work, we study upper respiratory tract gene expression to develop and validate a 2-gene host-based COVID-19 diagnostic classifier and then demonstrate its implementation in a clinically practical qPCR assay. We find that the host classifier has utility for mitigating false-negative results, for example due to SARS-CoV-2 variants harboring mutations at primer target sites, and for mitigating false-positive viral PCR results due to laboratory cross-contamination. Both types of error carry serious consequences of either unrecognized viral transmission or unnecessary isolation and contact tracing. This work is directly relevant to the ongoing COVID-19 pandemic given the continued emergence of viral variants and the continued challenges of false-positive PCR assays. It also suggests the feasibility of pan-respiratory virus host-based diagnostics that would have value in congregate settings, such as hospitals and nursing homes, where unrecognized respiratory viral transmission is of particular concern.

This paper highlights the value of pollen-analytical studies in the prehistoric archaeological context at the Fa Hien rock shelter. The Fa Hien rock shelter located in the Wet Zone of southwestern Sri Lanka has been occupied by the earliest anatomically modern humans in South Asia, dating from the late Pleistocene to the middle Holocene. The pollen evidence from the samples associated with the early Holocene human skeleton from this site has been used to assess the burial context and palynological taphonomy. Pollen data analysis indicates that high taphonomic impact occurred on the pollen grains in the depositional context, possibly due to reworking, burning, mechanical pressure and other possible human and animal activities. Furthermore, the pollen assemblage appears to have been primarily derived from the lowland rainforest, including disturbed habitats. Along with archaeological stratigraphy and radiometric dating, the pollen assemblage can be used to make broad inferences on the burial contexts and environment of the rock shelter occupants, while discussing the significance of forensic palynology in the Fa Hien archaeological context.

Background Pneumococcal serotypes differ in antimicrobial susceptibility. However, patterns and causes of this variation are not comprehensively understood. Methods We undertook a systematic review of epidemiologic studies of pneumococci isolated from carriage or invasive disease among children globally from 2000–2019. We evaluated associations of each serotype with nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. We evaluated differences in the prevalence of nonsusceptibility to major antibiotic classes across serotypes using random-effects meta-regression models and assessed changes in prevalence of nonsusceptibility after implementation of pneumococcal conjugate vaccines (PCVs). We also evaluated associations between biological characteristics of serotypes and their likelihood of nonsusceptibility to each drug. Results We included data from 129 studies representing 32 187 isolates across 52 countries. Within serotypes, the proportion of nonsusceptible isolates varied geographically and over time, in settings using and those not using PCVs. Factors predicting enhanced fitness of serotypes in colonization as well as enhanced pathogenicity were each associated with higher likelihood of nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole. Increases in prevalence of nonsusceptibility following PCV implementation were evident among non-PCV serotypes, including 6A, 6C, 15A, 15B/C, 19A, and 35B; however, this pattern was not universally evident among non-PCV serotypes. Postvaccination increases in nonsusceptibility for serotypes 6A and 19A were attenuated in settings that implemented PCV13. Conclusions In pneumococci, nonsusceptibility to penicillin, macrolides, and trimethoprim/sulfamethoxazole is associated with more frequent opportunities for antibiotic exposure during both prolonged carriage episodes and when serotypes cause disease. These findings suggest multiple pathways leading to resistance selection in pneumococci.

This study empirically estimates energy poverty levels across Queensland regions. It includes estimates of the number of households experiencing energy poverty in a region and the ability of households across regions to adapt to rising prices (price elasticity). We use these results to conduct a microsimulation exercise to examine how further rises in electricity prices could trigger a rise in energy poverty. It is estimated that 3.42% of all Queensland households – approximately 63,128 households – experience energy poverty, most of them being in the lowest income quintile. Energy poverty appears to be concentrated in certain regions, including Gladstone, Logan and Far North Queensland. A range of contributing factors may account for this pattern: high levels of income insecurity, weather and demographic differences. Beyond the distribution, our results also provide evidence that energy poverty is concentrated in certain groups, including large households. Policy implications are discussed.

PurposeWhile the monetary returns to education are well documented in the economics literature, the studies on non-monetary returns to education are scarce. The purpose of this study is to provide new insights into the non-market outcomes by exploring how education influences the food consumption choices of households and how these effects vary across different socio-economic groups using household-level calorie consumption data from Sri Lanka.Design/methodology/approachThis study uses two waves of Household Income and Expenditure Surveys – 2006/2007 and 2016. The methods adopted in analysing the data were descriptive statistics and the OLS regression model.FindingsThe empirical results show that educated poor households pay less per calorie compared to non-educated poor households, highlighting the role of education in improving the ability to make better food choices and manage household budgets more economically.Practical implicationsThis study informs policy-makers of the importance of education for formulating food and nutritional policies, which aim to raise the standard of living of resource-poor and vulnerable households in Sri Lanka as well as other developing countries with similar socio-economic conditions.Originality/valueTo the best of the authors' knowledge, this study is the first to explore the impact of education on the calorie consumption behaviour of people in the Sri Lankan context using nationwide household surveys.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/10.1108/IJSE-01-2022-0007

The twenty-first century has seen the emergence of many epidemic and pandemic viruses, with the most recent being the SARS-CoV-2-driven COVID-19 pandemic. As obligate intracellular parasites, viruses rely on host cells to replicate and produce progeny, resulting in complex virus and host dynamics during an infection. Single-cell RNA sequencing (scRNA-seq), by enabling broad and simultaneous profiling of both host and virus transcripts, represents a powerful technology to unravel the delicate balance between host and virus. In this review, we summarize technological and methodological advances in scRNA-seq and their applications to antiviral immunity. We highlight key scRNA-seq applications that have enabled the understanding of viral genomic and host response heterogeneity, differential responses of infected versus bystander cells, and intercellular communication networks. We expect further development of scRNA-seq technologies and analytical methods, combined with measurements of additional multi-omic modalities and increased availability of publicly accessible scRNA-seq datasets, to enable a better understanding of viral pathogenesis and enhance the development of antiviral therapeutics strategies.

Formulation of effective policies to enhance the resilience of tourism following the COVID-19 pandemic essentially requires comprehensive empirical information on changes in tourism demand and associated economic costs. The paper makes a novel contribution to tourism literature by employing regionally and temporally disaggregated tourism data and Google search data in improving the accuracy of tourism forecasts. Further, the paper adopts two timeseries variables namely tourist arrivals and guest nights in order to understand the changes due to COVID-19 in tourism demand more comprehensively. Monthly data on international tourist arrivals, guest nights and Google trends from 2004 to 2019 are used to produce regionally disaggregated (Europe, Asia, the Pacific, America, Other) monthly tourism forecasts for Sri Lanka. We find that SARMAX models outperform the other models (ARIMA, ARIMAX, SARIMA) in forecasting tourism demand following COVID-19. Interestingly, the paper makes a further step in utilizing forecasts in estimating foregone economic benefits due to COVID-19 pandemic. We find a notable difference in estimated direct economic loss depending on the variable used in estimates. The percentage loss is 40% when arrival forecasts are used in estimates and 29% when guest night forecasts are used in estimates. This provides important policy implications for improving post-COVID tourism.

Primary progressive aphasia (PPA) is a clinical syndrome in which patients progressively lose speech and language abilities. Three variants are recognized: logopenic (lvPPA), associated with phonology and/or short-term verbal memory deficits accompanied by left temporo-parietal atrophy; semantic (svPPA), associated with semantic deficits and anterior temporal lobe (ATL) atrophy; non-fluent (nfvPPA) associated with grammar and/or speech-motor deficits and inferior frontal gyrus (IFG) atrophy. Here, we set out to investigate whether the three variants of PPA can be dissociated based on error patterns in a single language task. We recruited 21 lvPPA, 28 svPPA, and 24 nfvPPA patients, together with 31 healthy controls, and analyzed their performance on an auditory noun-to-verb generation task, which requires auditory analysis of the input, access to and selection of relevant lexical and semantic knowledge, as well as preparation and execution of speech. Task accuracy differed across the three variants and controls, with lvPPA and nfvPPA having the lowest and highest accuracy, respectively. Critically, machine learning analysis of the different error types yielded above-chance classification of patients into their corresponding group. An analysis of the error types revealed clear variant-specific effects: lvPPA patients produced the highest percentage of “not-a-verb” responses and the highest number of semantically related nouns (production of baseball instead of throw to noun ball); in contrast, svPPA patients produced the highest percentage of “unrelated verb” responses and the highest number of light verbs (production of take instead of throw to noun ball). Taken together, our findings indicate that error patterns in an auditory verb generation task are associated with the breakdown of different neurocognitive mechanisms across PPA variants. Specifically, they corroborate the link between temporo-parietal regions with lexical processing, as well as ATL with semantic processes. These findings illustrate how the analysis of pattern of responses can help PPA phenotyping and heighten diagnostic sensitivity, while providing insights on the neural correlates of different components of language.

The COVID-19 pandemic, caused by the viral pathogen SARS-CoV-2, has taken the lives of millions of individuals around the world. Obesity is associated with adverse COVID-19 outcomes, but the underlying mechanism is unknown. In this report, we demonstrate that human adipose tissue from multiple depots is permissive to SARS-CoV-2 infection and that infection elicits an inflammatory response, including the secretion of known inflammatory mediators of severe COVID-19. We identify two cellular targets of SARS-CoV-2 infection in adipose tissue: mature adipocytes and adipose tissue macrophages. Adipose tissue macrophage infection is largely restricted to a highly inflammatory subpopulation of macrophages, present at baseline, that is further activated in response to SARS-CoV-2 infection. Preadipocytes, while not infected, adopt a proinflammatory phenotype. We further demonstrate that SARS-CoV-2 RNA is detectable in adipocytes in COVID-19 autopsy cases and is associated with an inflammatory infiltrate. Collectively, our findings indicate that adipose tissue supports SARS-CoV-2 infection and pathogenic inflammation and may explain the link between obesity and severe COVID-19.One sentence summaryOur work provides the first in vivo evidence of SARS-CoV-2 infection in human adipose tissue and describes the associated inflammation.

Summary Background Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation. Methods We did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer). Population-based studies of invasive pneumococcal disease or nasopharyngeal colonisation were eligible for inclusion. As primary outcome measures, we extracted the proportions of isolates that were non-susceptible or resistant to penicillin, macrolides, sulfamethoxazole–trimethoprim, third-generation cephalosporins, and tetracycline from each study. Where available, we also extracted data on pneumococcal serotypes. We estimated changes in the proportion of isolates with reduced susceptibility or resistance to each antibiotic class using random-effects meta-regression models, adjusting for study-level and region-level heterogeneity, as well as secular trends, invasive or colonising isolate source, and countries' per-capita gross domestic product. Findings From 4910 studies screened for inclusion, we extracted data from 559 studies on 312 783 paediatric isolates. Susceptibility of isolates varied substantially across regions both before and after implementation of any PCV product. On average across all regions, we estimated significant absolute reductions in the proportions of pneumococci showing non-susceptibility to penicillin (11·5%, 95% CI 8·6–14·4), sulfamethoxazole–trimethoprim (9·7%, 4·3–15·2), and third-generation cephalosporins (7·5%, 3·1–11·9), over the 10 years after implementation of any PCV product, and absolute reductions in the proportions of pneumococci resistant to penicillin (7·3%, 5·3–9·4), sulfamethoxazole–trimethoprim (16·0%, 11·0–21·2), third-generation cephalosporins (4·5%, 0·3–8·7), macrolides (3·6%, 0·7–6·6) and tetracycline (2·0%, 0·3–3·7). We did not find evidence of changes in the proportion of isolates non-susceptible to macrolides or tetracycline after PCV implementation. Observed changes in penicillin non-susceptibility were driven, in part, by replacement of vaccine-targeted serotypes with non-vaccine serotypes that were less likely to be non-susceptible. Interpretation Implementation of PCVs has reduced the proportion of circulating pneumococci resistant to first-line antibiotic treatments for pneumonia. This effect merits consideration in assessments of vaccine impact and investments in coverage improvements. Funding Bill & Melinda Gates Foundation.

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults and only rarely in children. To investigate whether differences in the upper airway immune response could contribute to this disparity, we compared nasopharyngeal gene expression in 83 children (40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes (ISGs) was robustly activated in both children and adults with SARS-CoV-2 compared to the respective non-viral groups, with only relatively subtle distinctions. Children, however, demonstrated markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including TNF, IFNγ, IL-2 and IL-4 production. Cell type deconvolution confirmed greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibited a decrease in proportions of ciliated cells, the primary target of SARS-CoV-2, upon infection with the virus. These findings demonstrate that children elicit a more robust innate and adaptive immune response to SARS-CoV-2 infection in the upper airway that likely contributes to their protection from severe disease in the lower airway.

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children (40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.

Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults and only rarely in children. To investigate whether differences in the upper airway immune response could contribute to this disparity, we compared nasopharyngeal gene expression in 83 children (40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes (ISGs) was robustly activated in both children and adults with SARS-CoV-2 compared to the respective non-viral groups, with only relatively subtle distinctions. Children, however, demonstrated markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including TNF, IFNγ, IL-2 and IL-4 production. Cell type deconvolution confirmed greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibited a decrease in proportions of ciliated cells, the primary target of SARS-CoV-2, upon infection with the virus. These findings demonstrate that children elicit a more robust innate and adaptive immune response to SARS-CoV-2 infection in the upper airway that likely contributes to their protection from severe disease in the lower airway.

Pyrethroid insecticides are widely used to control mosquitoes that transmit diseases such as West Nile virus (WNV) to humans. A single nucleotide polymorphism (SNP) in the knockdown resistance locus (kdr) of the voltage gated sodium channel (Vgsc) gene of Culex mosquitoes confers knockdown resistance to pyrethroids. PCR-based assays that detect these SNPs in Culex species are currently available for Culex pipiens Linnaeus and Culex quinquefasciatus Say. RNAseq was employed to sequence the coding region of Vgsc for Culex tarsalis Coquillett and Culex erythrothorax Dyar, two WNV vectors. We utilized the cDNA sequence to develop a quantitative reverse transcriptase PCR assay that detects the L1014F mutation in the kdr of Vgsc. Because this locus is conserved, the assay successfully detected the SNPs in multiple Culex spp. vectors of WNV in the United States. The resulting Culex RTkdr assay was validated using quantitative PCR, CDC bottle bioassays, and sequencing of PCR products. Using sequencing, we determined the accuracy of the Culex RTkdr assay was 99%. Pyrethroid resistance was more common among Cx. pipiens than other Culex spp. and co-occured with agriculture. We anticipate that public health and vector control agencies may utilize the Culex RTkdr assay to map the distribution of pyrethroid resistance in Culex species to more efficiently control mosquitoes and the diseases they transmit.

Pyrethroid insecticides are widely used to control mosquitoes that transmit pathogens such as West Nile virus (WNV) to people. Single nucleotide polymorphisms (SNP) in the knockdown resistance locus (kdr) of the voltage gated sodium channel (Vgsc) gene in Culex mosquitoes are associated with knockdown resistance to pyrethroids. RNAseq was used to sequence the coding region of Vgsc for Culex tarsalis Coquillett and Culex erythrothorax Dyar, two WNV vectors. The cDNA sequences were used to develop a quantitative reverse transcriptase PCR assay that detects the L1014F kdr mutation in the Vgsc. Because this locus is conserved, the assay was used successfully in six Culex spp. The resulting Culex RTkdr assay was validated using quantitative PCR and sequencing of PCR products. The accuracy of the Culex RTkdr assay was 99%. The L1014F kdr mutation associated with pyrethroid resistance was more common among Cx. pipiens than other Culex spp. and was more prevalent in mosquitoes collected near farmland. The Culex RTkdr assay takes advantage of the RNA that vector control agencies routinely isolate to assess arbovirus prevalence in mosquitoes. We anticipate that public health and vector control agencies may employ the Culex RTkdr assay to define the geographic distribution of the L1014F kdr mutation in Culex species and improve the monitoring of insecticide resistance that will ultimately contribute to effective control of Culex mosquitoes.

In the extensive literature on the role of government in the economy scant attention has been paid to the influence of the relative size of government on an economy’s rate of growth. This paper canvasses perspectives on why the size of government has grown, how this affects the wider economy, and why a trade-off exists between increased government size and economic growth beyond some optimal level, as conveyed by the so-called BARS curve. The paper next examines in-depth trends in government spending in Australia which has grown to a historically high level of 37 per cent of national income post GFC before econometrically estimating the optimal size of government on Australia’s BARS curve using the ARMAX approach. The results suggest the share of government spending in Australia consistent with maximising economic growth is 31 per cent of national income, significantly below the current level.

Mosquitoes are major infectious disease-carrying vectors. Assessment of current and future risks associated with the mosquito population requires knowledge of the full repertoire of pathogens they carry, including novel viruses, as well as their blood meal sources. Unbiased metatranscriptomic sequencing of individual mosquitoes offers a straightforward, rapid and quantitative means to acquire this information. Here, we profile 148 diverse wild-caught mosquitoes collected in California and detect sequences from eukaryotes, prokaryotes, 24 known and 46 novel viral species. Importantly, sequencing individuals greatly enhanced the value of the biological information obtained. It allowed us to a) speciate host mosquito, b) compute the prevalence of each microbe and recognize a high frequency of viral co-infections, c) associate animal pathogens with specific blood meal sources, and d) apply simple co-occurrence methods to recover previously undetected components of highly prevalent segmented viruses. In the context of emerging diseases, where knowledge about vectors, pathogens, and reservoirs is lacking, the approaches described here can provide actionable information for public health surveillance and intervention decisions.

BackgroundMost data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have been presented as case series without comparison to patients with other acute respiratory illnesses.MethodsWe examined emergency department patients between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared clinical presentation, diagnostics, treatment, and outcomes.FindingsAmong 316 patients, 33 tested positive for SARS-CoV-2; 31 without COVID-19 tested positive for another respiratory virus. Among patients with additional viral testing (27/33), no SARS-CoV-2 co-infections were identified. Compared to those who tested negative, patients with COVID-19 reported longer symptoms duration (median 7d vs. 3d, p&nbsp

AIM To identify the association between hours of being barefoot/wearing footwear, physical activity (PA) and knee osteoarthritis pain flares (KOAF). METHODS Persons with a diagnosis of knee osteoarthritis, who reported previous KOAF, were followed up in a 3 months long telephone-based case-crossover study. Exposures to risk factors were assessed every 10 days and whenever the participants experienced a KOAF. Conditional logistic regression examined associations of KOAF with following: hours of being barefoot/using footwear and PA performed (P

Author(s): Shah, Sachin J; Barish, Peter N; Prasad, Priya A; Kistler, Amy L; Neff, Norma; Kamm, Jack; Li, Lucy M; Chiu, Charles Y; Babick, Jennifer M; Fang, Margaret C; Abe-Jones, Yumiko; Alipanah, Narges; Alvarez, Francisco N; Botvinnik, Olga B; Davis, Jennifer M; Castenada, Gloria D; Consortium, CLIAHub; Dadasovich, Rand M; Deng, Xianding; DeRisi, Joseph L; Detweiler, Angela M; Federman, Scot; Haliburton, John R; Hao, Samantha L; Kerkhoff, Andrew D; Kumar, Renuka; Malcolm, Katherine; Mann, Sabrina A; Martinez, Sandra P; Marya, Rupa; Mick, Eran; Mwakibete, Lusajo L; Najafi, Nader; Peluso, Michael J; Phelps, Maira S; Pisco, Angela O; Ratnasiri, Kalani; Rubio, Luis A; Sellas, Anna B; Sherwood, Kyla D; Sheu, Jonathan; Spottiswoode, Natasha; Tan, Michelle; Yu, Guixa; Kangelaris, Kirsten N; Langelier, Charles | Abstract: BACKGROUND:Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS:We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS:In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); pl0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, pl0.001) and were more likely to develop ARDS (23% vs. 3%, pl0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. INTERPRETATION:While we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses. .

OBJECTIVE To analyze the difficulties and challenges arising from introduction of postpartum intrauterine device (PPIUD) services into the Sri Lankan health system. METHODS Phase I of a FIGO PPIUD initiative was implemented in 2013 in six hospitals; phase II began in 12 hospitals in 2015. During this period, 915 Medical Officers were trained in PPIUD insertion and 5370 personnel were trained in PPIUD counseling. Women were followed up at 4-6 weeks after insertion. RESULTS A total of 184 433 women (62.4% of hospital deliveries) were interviewed about PPIUD as a method of contraception. Of those interviewed, 116 159 (63.0%) received counseling on PPIUD and 11 339 (6.1%) consented to PPIUD insertion. Of consenting women, 9346 (82.4%) had a PPIUD inserted. There were no significant complications reported at insertion. Expulsion rates were 2.9% and removal rates were 4.1%. CONCLUSION PPIUD as a method of contraception was successfully introduced into the 18 participating hospitals. Given the success of this pilot intervention and the safety profile demonstrated, PPIUD was added to the national family planning program in 2017.

Purpose The purpose of this paper is to explore the effect of agricultural extension services provided by public sector on the individual technology adoption behaviour of rice farmers in Sri Lanka. Design/methodology/approach The study used data from a cross sectional survey conducted in seven rice procuring regions in Sri Lanka. Eight rice technologies were selected to explore the effect of extension service on adoption behaviour of rice farmers using probit models. The extension service variable was identified as potentially endogeneous and instrumented using average extension for each region. Findings The results revealed that the extension service variable was positive and indicative of a high level of significance in all the rice technologies promoting the adoption. Hence the public agricultural extension service programmes were considered as significant explanators of technology adoption. The farmers who received agricultural extension service were more likely to adopt a technology. Social implications At present, the position of agricultural extension service is questioned and the future is unknown. Therefore, this study advises policy makers to prioritise agricultural policies to strengthen public spending on agricultural extension for effective adoption of technological innovations. Originality/value The paper adds solid empirical evidence to the literature on technology adoption behaviour from a peasant agricultural context in a developing country scenario that uses farm level data. Moreover, the study contributes to the literature by reiterating the significance of public provision of extension and training programmes as a direct motive in the technology adoption behaviour of farmers.

This paper explores how the household’s capacity to grow food impacts their ability to achieve economies of scale in food consumption and how this impacts the geographic distribution of poverty across rural and urban areas. An accurate understanding of consumption economies of scale is vital for comparing poverty levels across households of varying size. Using Sri Lankan data on home-grown food consumption, we empirically confirm that such economies of scale exist and that large households tend to consume relatively more home-grown food than smaller households. The magnitude of these scale economies are found to be larger than those in market purchased food, but smaller than those found in housing expenditure. Consuming more home-grown food is also found to be positively correlated with per-capita calories consumed. Taking these effects into account in poverty estimates leads to a 15 per cent decline in the number of household who fall below the poverty line in rural regions.

This paper examines the nexus between excess currency growth and inflation in Australia. It first canvasses the operation of monetary policy. Using different econometric techniques, it next examines how well excess money supply growth, measured in terms of currency and M3, explains Australia's inflation over the long term from 1970–2015, and then more specifically before and after the adoption of inflation targeting. Its key result is that excess money growth has been the main determinant of Australia's inflation, although became less important during the inflation targeting era. This implies the velocity of currency, the sine qua non of the Quantity Theory of Money, has been remarkably stable. Given the role excess currency plays in generating Australian inflation, it should be afforded greater prominence in monetary policy deliberations.

While it is well known that new technologies enhance consumer welfare, the manner in which these technologies impact the ability to realize economies of scale in consumption is not well understood. We use Sri Lankan household data to examine how the adoption of new technologies by households positively impacts their ability to achieve household economies of scale. This suggests that new technologies not only deliver a greater variety of consumption goods to consumers, but they may also play an important role in enabling large households to escape poverty by lowering the per-capita costs of maintaining a given standard of living. Given the importance of consumption economies of scale in the measurement of poverty, this study provides some insights on the extent to which the number of poor households changes when food consumption scale economies due to technology adoption in the domestic sphere are incorporated.

This paper focuses on Vietnam's exchange rate whose official rate has been pegged by the State Bank against the US dollar since 1989 despite wider market liberalisation over this time. Whether Vietnam's official exchange rate is appropriately valued has important implications for the economy's international competitiveness, trade balance and gross domestic product (GDP). The main aim of the paper is to assess whether the official exchange rate has been valued appropriately with reference to macroeconomic fundamentals, as proposed by the purchasing power parity and the behavioural equilibrium exchange rate approaches to evaluating equilibrium exchange rates. Our main empirical finding based on co-integration analysis using quarterly data from 1995 to 2014 is that according to both these approaches the Vietnamese Dong was significantly overvalued for extended times, most notably due to Vietnam's relatively high inflation rate.

Purpose The purpose of this paper is to test whether household preferences satisfy the assumption of base-independence, to examine the effects of household income on equivalence scales and thereby food consumption economies of scale and to examine how far conventional poverty rates require adjustment when scale economies in food consumption are taken into consideration. Design/methodology/approach To achieve these aims, the authors use a Pendakur (1999) adaptation of the test of base-independence, and income dependent Engel (1895) equivalence scales. Findings In Sri Lanka, the hypothesis of base-independence is rejected: the equivalence scales increase with household income both at the national and the sectoral level, that is urban, rural and estate sectors. This suggests that low-income households enjoy greater scale economies. After adjusting for scale economies, urban, rural and estate poverty headcount ratios decline by 3.2, 8.8 and 13.7, respectively, while at the national level the decline is about 8.3. Research limitations/implications The results are based on the assumption that all of the adults in the households have identical tastes, irrespective of their gender and age. Furthermore, the survey data exclude three districts in the northern province of Sri Lanka due to resettlement activities took place after the civil war. Practical implications Higher scale economies among the poor imply that poverty among low-income households is overstated when using traditional measures of poverty rates. Originality/value The novelty of this paper is that it provides insights on the effect of income on food consumption economies of scale and implications of this phenomenon on poverty estimates in the context of a developing country like Sri Lanka.

To describe trends in the incidence and severity of meconium aspiration syndrome (MAS) around the release of revised Neonatal Resuscitation Program (NRP) guidelines in 2016. The California Perinatal Quality Care Collaborative database was queried for years 2013–2017 to describe the incidence and outcomes of infants with MAS. Results were analyzed based on both individual years and pre- vs. post-guideline epochs (2013–15 vs. 2017). Incidence of MAS decreased significantly from 2013–15 to 2017 (1.02 to 0.78/1000 births, p

ObjectiveTo determine recent trends in maternal prepregnancy body mass index (BMI) and to quantify its association with birth and maternal outcomes.MethodsA population-based retrospective cohort study included resident women with singleton births in the California Birth Statistical Master Files (BSMF) database from 2007 to 2016. There were 4,621,082 women included out of 5,054,968 women registered in the database. 433,886 (8.6%) women were excluded due to invalid or missing information for BMI. Exposures were underweight (BMI < 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥ 30 kg/m2) at the onset of pregnancy. Obesity was subcategorized into class I (30.0-34.9 kg/m2), class II (35.0-39.9 kg/m2), and class III (≥ 40 kg/m2), while adverse outcomes examined were low birth weight (LBW), very low birth weight (VLBW), macrosomic births, preterm birth (PTB), very preterm birth (VPTB), small-for-gestational-age birth (SGA), large-for-gestational-age birth (LGA), and cesarean delivery (CD). Descriptive analysis, simple linear regression, and multivariate logistic regression were performed, and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations were estimated.ResultsOver the ten-year study period, the prevalence of underweight and normal weight women at time of birth declined by 10.6% and 9.7%, respectively, while the prevalence of overweight and obese increased by 4.3% and 22.9%, respectively. VLBW increased significantly with increasing BMI, by 24% in overweight women and by 76% in women with class III obesity from 2007 to 2016. Women with class III obesity also had a significant increase in macrosomic birth (170%) and were more likely to deliver PTB (33%), VPTB (66%), LGA (231%), and CD (208%) than women with a normal BMI. However, obese women were less likely to have SGA infants; underweight women were 51% more likely to have SGA infants than women with a normal BMI.ConclusionsIn California from 2007 to 2016, there was a declining trend in women with prepregnancy normal weight, and a rising trend in overweight and obese women, particularly obesity class III. Both extremes of prepregnancy BMI were associated with an increased incidence of adverse neonatal outcomes; however, the worse outcomes were prominent in those women classified as obese.

This study analyses asymmetry in price transmission between wholesale and retail rice markets in Sri Lanka, using the threshold autoregressive model. We found that the wholesale and the retail rice markets in Sri Lanka are integrated, with price changes moving from the wholesale to the retail market. However, the price transmission process is asymmetric. In particular, price increases at the wholesale market transmit immediately to the retail market while price decreases transmit more slowly. Parameter stability test and follow-up analysis indicated that the price transmission process is asymmetric only during periods of price surges, suggesting that the rice market is not efficient during these periods.