ABSTRACT
Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak-between 14 February and 19 June 2021-near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization.
Subject(s)
Disease Outbreaks , Ebolavirus/genetics , Ebolavirus/isolation & purification , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/virology , Models, Biological , Animals , Democratic Republic of the Congo/epidemiology , Disease Outbreaks/statistics & numerical data , Ebolavirus/classification , Female , Guinea/epidemiology , Hemorrhagic Fever, Ebola/transmission , High-Throughput Nucleotide Sequencing , Humans , Male , Persistent Infection/virology , Phylogeny , Survivors , Time Factors , Viral Zoonoses/transmission , Viral Zoonoses/virologyABSTRACT
Diffuse correlation spectroscopy (DCS) is a powerful tool for assessing microvascular hemodynamic in deep tissues. Recent advances in sensors, lasers, and deep learning have further boosted the development of new DCS methods. However, newcomers might feel overwhelmed, not only by the already-complex DCS theoretical framework but also by the broad range of component options and system architectures. To facilitate new entry to this exciting field, we present a comprehensive review of DCS hardware architectures (continuous-wave, frequency-domain, and time-domain) and summarize corresponding theoretical models. Further, we discuss new applications of highly integrated silicon single-photon avalanche diode (SPAD) sensors in DCS, compare SPADs with existing sensors, and review other components (lasers, sensors, and correlators), as well as data analysis tools, including deep learning. Potential applications in medical diagnosis are discussed and an outlook for the future directions is provided, to offer effective guidance to embark on DCS research.
ABSTRACT
Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.
Subject(s)
Early Detection of Cancer , HIV Infections , Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/diagnosis , Papillomavirus Infections/virology , Papillomavirus Infections/diagnosis , Papillomavirus Infections/complications , Early Detection of Cancer/methods , HIV Infections/virology , HIV Infections/diagnosis , HIV Infections/complications , HIV Infections/metabolism , Adult , Middle Aged , Oncogene Proteins, Viral/genetics , Oncogene Proteins, Viral/metabolism , Developing Countries , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Latin America/epidemiology , DNA, Viral/analysis , DNA, Viral/genetics , Africa/epidemiologyABSTRACT
Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and gene polymorphism's influence on the IL-17A serum levels. In this research, 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum levels and malaria outcomes. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P < 0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients, indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (AA). According to our results, it can be concluded that the IL-17A gene rs8193038 polymorphism significantly affects IL-17A gene expression. Our results fill a gap in the implication of IL-17A gene polymorphisms on the cytokine level in a malaria cohort. IL-17A gene polymorphisms also may influence cytokine production in response to Plasmodium infections and may contribute to the hyperinflammatory responses during severe malaria outcomes.
Subject(s)
Interleukin-17 , Malaria , Humans , Interleukin-17/genetics , Malaria/genetics , Gene Frequency , Polymorphism, Genetic , CytokinesABSTRACT
Nowadays, biomarkers are recognized as valuable tools to complement chemical and ecological assessments in biomonitoring programs. They provide insights into the effects of contaminant exposures on individuals and establish connections between environmental pressure and biological response at higher levels. In the last decade, strong improvements in the design of experimental protocols and the result interpretation facilitated the use of biomarker across wide geographical areas, including aquatic continua. Notably, the statistical establishment of reference values and thresholds enabled the discrimination of contamination effects in environmental conditions, allowed interspecies comparisons, and eliminated the need of a reference site. The aim of this work was to study freshwater-estuarine-coastal water continua by applying biomarker measurements in multi-species caged organisms. During two campaigns, eight sentinel species, encompassing fish, mollusks, and crustaceans, were deployed to cover 25 sites from rivers to the sea. As much as possible, a common methodology was employed for biomarker measurements (DNA damage and phagocytosis efficiency) and data interpretation based on guidelines established using reference values and induction/inhibition thresholds (establishment of three effect levels). The methodology was successfully implemented and allowed us to assess the environmental quality. Employing multiple species per site enhances confidence in observed trends. The results highlight the feasibility of integrating biomarker-based environmental monitoring programs across a continuum scale. Biomarker results align with Water Framework Directive indicators in cases of poor site quality. Additionally, when discrepancies arise between chemical and ecological statuses, biomarker findings offer a comprehensive perspective to elucidate the disparities. Presented as a pilot project, this work contributes to gain insights into current biomonitoring needs, providing new questions and perspectives.
Subject(s)
Biomarkers , Environmental Monitoring , Sentinel Species , Environmental Monitoring/methods , Biomarkers/analysis , France , Animals , FishesABSTRACT
BACKGROUND: Nirmatrelvir/ritonavir has shown to reduce COVID-19 hospitalization and death before Omicron, but updated real-world evidence studies are needed. This study aimed to assess whether nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among high-risk outpatients. METHODS: A retrospective cohort study of outpatients with SARS-CoV-2 between March 15 and 15 October 2022, using data from the Quebec clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared with infected ones not receiving nirmatrelvir/ritonavir using propensity-score matching. Relative risk (RR) of COVID-19-associated hospitalization within 30 days was assessed using a Poisson regression. RESULTS: A total of 8402 treated outpatients were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir treatment was associated with a 69% reduced RR of hospitalization (RR: .31; 95% CI: .28; .36; number needed to treat [NNT] = 13). The effect was more pronounced in outpatients with incomplete primary vaccination (RR: .04; 95% CI: .03; .06; NNT = 8), while no benefit was found in those with a complete primary vaccination (RR: .93; 95% CI: .78; 1.08). Subgroups analysis among high-risk outpatients with a complete primary vaccination showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in the RR of hospitalization in severely immunocompromised outpatients (RR: .66; 95% CI: .50; .89; NNT = 16) and in high-risk outpatients aged ≥70 years (RR: .50; 95% CI: .34; .74; NNT = 10) when the last dose of the vaccine was received at least 6 months ago. CONCLUSIONS: Nirmatrelvir/ritonavir reduces the risk of COVID-19-associated hospitalization among incompletely vaccinated high-risk outpatients and among some subgroups of completely vaccinated high-risk outpatients.
Subject(s)
COVID-19 , Ritonavir , Humans , Quebec/epidemiology , Cohort Studies , Retrospective Studies , Ritonavir/therapeutic use , COVID-19/prevention & control , SARS-CoV-2 , COVID-19 Drug Treatment , Hospitalization , Antiviral Agents/therapeutic useABSTRACT
Magnetic resonance imaging (MRI) technology has profoundly transformed current healthcare systems globally, owing to advances in hardware and software research innovations. Despite these advances, MRI remains largely inaccessible to clinicians, patients, and researchers in low-resource areas, such as Africa. The rapidly growing burden of noncommunicable diseases in Africa underscores the importance of improving access to MRI equipment as well as training and research opportunities on the continent. The Consortium for Advancement of MRI Education and Research in Africa (CAMERA) is a network of African biomedical imaging experts and global partners, implementing novel strategies to advance MRI access and research in Africa. Upon its inception in 2019, CAMERA sets out to identify challenges to MRI usage and provide a framework for addressing MRI needs in the region. To this end, CAMERA conducted a needs assessment survey (NAS) and a series of symposia at international MRI society meetings over a 2-year period. The 68-question NAS was distributed to MRI users in Africa and was completed by 157 clinicians and scientists from across Sub-Saharan Africa (SSA). On average, the number of MRI scanners per million people remained at less than one, of which 39% were obsolete low-field systems but still in use to meet daily clinical needs. The feasibility of coupling stable energy supplies from various sources has contributed to the growing number of higher-field (1.5 T) MRI scanners in the region. However, these systems are underutilized, with only 8% of facilities reporting clinical scans of 15 or more patients per day, per scanner. The most frequently reported MRI scans were neurological and musculoskeletal. The CAMERA NAS combined with the World Health Organization and International Atomic Energy Agency data provides the most up-to-date data on MRI density in Africa and offers a unique insight into Africa's MRI needs. Reported gaps in training, maintenance, and research capacity indicate ongoing challenges in providing sustainable high-value MRI access in SSA. Findings from the NAS and focused discussions at international MRI society meetings provided the basis for the framework presented here for advancing MRI capacity in SSA. While these findings pertain to SSA, the framework provides a model for advancing imaging needs in other low-resource settings.
Subject(s)
Magnetic Resonance Imaging , Humans , Africa South of the Sahara , Surveys and QuestionnairesABSTRACT
The Gobra zebu genetic breeding program has resulted in the genetic improvement of a new population. This population gained genetic characteristics that set them apart from the other cattle populations reared in Senegal. The cause of these differences might be the reproductive isolation and selection to which this population of the "Centre de Recherches Zootechniques" of Dahra has been subjected since the 1950s. This study aimed to assess the genetic differentiation and structuration of this population compared to the main cattle breeds used in Senegal. A total of 180 individuals, selected from the Gobra selection nucleus and bovine populations from four main breeds in Senegal, were included in this study. We used a panel of 21 microsatellite markers among those recommended by the Food Agriculture Organization, to conduct the molecular genotyping of our sampled populations. The basic genetic parameters of differentiation and structuration were calculated using various bioinformatics software. The results of this study, particularly the degrees of genetic differentiation (Fst), the coefficient of genetic homogeneity (Gst), and the gene flow (Nm), show a significant genetic differentiation of the Gobra from the station compared to the other populations studied. Structuring and phylogeny analyses reveal a micro-structuring within the Gobra population as a novelty. This micro-structuring clearly identifies the Gobra individuals from Dahra's station among the other Gobra populations studied. The main causes of these observations would be reproductive isolation and the selection pressure exerted on this population for several decades.
Subject(s)
Breeding , Genetic Drift , Humans , Cattle/genetics , Animals , Senegal , Microsatellite Repeats , Genetic VariationABSTRACT
BACKGROUND: Cervical cancer is a significant public health problem, with 570,000 new cases and 300,000 deaths of women per year globally, mostly in low- and middle-income countries. In 2018 the WHO Director General made a call to action for the elimination of cervical cancer as a public health problem. MAIN BODY: New thinking on programmatic approaches to introduce emerging technologies and screening and treatment interventions of cervical precancer at scale is needed to achieve elimination goals. Implementation research (IR) is an important yet underused tool for facilitating scale-up of evidence-based screening and treatment interventions, as most research has focused on developing and evaluating new interventions. It is time for countries to define their specific IR needs to understand acceptability, feasibility, and cost-effectiveness of interventions as to design and ensure effective implementation, scale-up, and sustainability of evidence-based screening and treatment interventions. WHO convened an expert advisory group to identify priority IR questions for HPV-based screening and treatment interventions in population-based programmes. Several international organizations are supporting large scale introduction of screen-and-treat approaches in many countries, providing ideal platforms to evaluate different approaches and strategies in diverse national contexts. CONCLUSION: For reducing cervical cancer incidence and mortality, the readiness of health systems, the reach and effectiveness of new technologies and algorithms for increasing screening and treatment coverage, and the factors that support sustainability of these programmes need to be better understood. Answering these key IR questions could provide actionable guidance for countries seeking to implement the WHO Global Strategy towards cervical cancer elimination.
Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Incidence , Income , Mass Screening , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , VaccinationABSTRACT
OBJECTIVES: With the perspective of prophylactic vaccination against high-risk human papillomavirus (HPV), we analyzed the viral epidemiology of cervical neoplasia in Senegal. METHODS: All patients were treated at the Institut Joliot Curie du Cancer in Dakar. HPV genotypes were characterized using a real-time polymerase chain reaction-based approach and sequencing. RESULTS: Histologically, there were 224 invasive carcinomas, 17 high-grade intraepithelial neoplasia (CIN), and five undetermined histologies. Molecular analysis was conclusive in 241 cases. HPV DNA was found in 207/241 (85.9%) cases while 34/241 (14.1%) remained HPV negative. There was one single genotype in 127/207 (61.4%) cases and several in 80/207 (38.6%) corresponding to 308 genotypes identified. Viral genotyping found HPV16 in 175 (56.8%) cases, HPV18 in 45 (14.6%), HPV45 in 40 (13.0%), HPV58 in 35 (11.4%), HPV33 in 6 (2.0%), HPV35 in 3 (1.0%), HPV31 in 2 (0.6%), HPV39 and HPV56 in one (0.3% each). CONCLUSION: Our analysis showed that 98.4% of the HPV-positive cases were associated with viral genotypes covered by the 9-valent HPV vaccine. However, 14.1% of cases remained HPV negative. Therefore, prophylactic vaccination using a 9-valent vaccine should dramatically reduce the incidence of HPV-associated neoplasia but the detection and treatment of CIN remain necessary for the optimal prevention of cervical cancer.
Subject(s)
Papillomaviridae/genetics , Papillomavirus Infections/virology , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/virology , Adult , Female , Genotype , Humans , Middle Aged , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Papillomavirus Infections/pathology , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/genetics , Prevalence , Senegal/epidemiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/prevention & controlABSTRACT
Phase-shifting profilometry (PSP) is considered to be the most accurate technique for phase retrieval with fringe projection profilometry (FPP) systems. However, PSP requires that multiple phase-shifted fringe patterns be acquired, usually sequentially, which has limited PSP to static or quasi-static imaging. In this paper, we introduce multispectral 4-step phase-shifting FPP that provides 3D imaging using a single acquisition. The method enables real-time profilometry applications. A single frame provides all four phase-shifted fringe patterns needed for the PSP phase retrieval algorithm. The multispectral nature of the system ensures that light does not leak between the spectral bands, which is a common problem in simultaneous phase-shifting with color cameras. With the use of this new concept, custom composite patterns containing multiple patterns can be acquired with a single acquisition.
ABSTRACT
BACKGROUND: Dengue fever is a mosquito born disease associated with self-limited to life threatening illness. First detected in Senegal in the nineteenth century, and despite its growing incidence this last decade, significant knowledge gaps exist in our knowledge of genetic diversity of circulating strains. This study highlights the circulating serotypes and genotypes between January 2017 and December 2018 and their spatial and temporal distribution throughout all regions of Senegal. METHODS: We used 56 dengue virus (DENV) strains for the analysis collected from 11 sampling areas: 39 from all regions of Senegal, and 17 isolates from Thiès, a particular area of the country. Two real time RT-qPCR systems were used to confirm dengue infection and corresponding serotypes. For molecular characterization, CprM gene was sequenced and submitted to phylogenetic analysis for serotypes and genotypes assignment. RESULTS: Three dengue virus serotypes (DENV-1-3) were detected by all used methods. DENV-3 was detected in 50% (28/56) of the isolates, followed by DENV-1 and DENV-2, each representing 25% (14/56) of the isolates. DENV-3 belongs to genotype III, DENV-1 to genotype V and DENV-2 to Cosmopolitan genotype. Serotype 3 was detected in 7 sampling locations and a co-circulation of different serotypes was observed in Thiès, Fatick and Richard-toll. CONCLUSIONS: These results emphasize the need of continuous DENV surveillance in Senegal to detect DENV cases, to define circulating serotypes/genotypes and to prevent the spread and the occurrence of severe cases.
Subject(s)
Dengue Virus/genetics , Dengue/epidemiology , Dengue/diagnosis , Dengue Virus/isolation & purification , Humans , Phylogeny , Public Health Surveillance , Senegal/epidemiology , Serogroup , Spatial AnalysisABSTRACT
This is the first multimodal study of cerebral tissue metabolism and perfusion post-hypoxic-ischaemic (HI) brain injury using broadband near-infrared spectroscopy (bNIRS), diffuse correlation spectroscopy (DCS), positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). In seven piglet preclinical models of neonatal HI, we measured cerebral tissue saturation (StO2), cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), changes in the mitochondrial oxidation state of cytochrome c oxidase (oxCCO), cerebral glucose metabolism (CMRglc) and tissue biochemistry (Lac+Thr/tNAA). At baseline, the parameters measured in the piglets that experience HI (not controls) were 64 ± 6% StO2, 35 ± 11 ml/100 g/min CBF and 2.0 ± 0.4 µmol/100 g/min CMRO2. After HI, the parameters measured were 68 ± 6% StO2, 35 ± 6 ml/100 g/min CBF, 1.3 ± 0.1 µmol/100 g/min CMRO2, 0.4 ± 0.2 Lac+Thr/tNAA and 9.5 ± 2.0 CMRglc. This study demonstrates the capacity of a multimodal set-up to interrogate the pathophysiology of HIE using a combination of optical methods, MRS, and PET.
Subject(s)
Hypoxia-Ischemia, Brain , Animals , Brain/diagnostic imaging , Cerebrovascular Circulation , Hypoxia-Ischemia, Brain/diagnostic imaging , Oxygen , Oxygen Consumption , Perfusion , Spectroscopy, Near-Infrared , SwineABSTRACT
PURPOSE: There is a need for bedside methods to monitor oxygen delivery in the microcirculation. Near-infrared spectroscopy commonly measures tissue oxygen saturation, but does not reflect the time-dependent variability of microvascular hemoglobin content (MHC) that attempts to match oxygen supply with demand. The objective of this study is to determine the feasibility of MHC monitoring in critically ill patients using high-resolution near-infrared spectroscopy to assess perfusion in the peripheral microcirculation. METHODS: Prospective observational cohort of 36 patients admitted within 48 h at a tertiary intensive care unit. Perfusion was measured on the quadriceps, biceps, and/or deltoid, using the temporal change in optical density at the isosbestic wavelength of hemoglobin (798 nm). Continuous wavelet transform was applied to the hemoglobin signal to delineate frequency ranges corresponding to physiological oscillations in the cardiovascular system. RESULTS: 31/36 patients had adequate signal quality for analysis, most commonly affected by motion artifacts. MHC signal demonstrates inter-subject heterogeneity in the cohort, indicated by different patterns of variability and frequency composition. Signal characteristics were concordant between muscle groups in the same patient, and correlated with systemic hemoglobin levels and oxygen saturation. Signal power was lower for patients receiving vasopressors, but not correlated with mean arterial pressure. Mechanical ventilation directly impacts MHC in peripheral tissue. CONCLUSION: MHC can be measured continuously in the ICU with high-resolution near-infrared spectroscopy, and reflects the dynamic variability of hemoglobin distribution in the microcirculation. Results suggest this novel hemodynamic metric should be further evaluated for diagnosing microvascular dysfunction and monitoring peripheral perfusion.
Subject(s)
Hemoglobins , Intensive Care Units , Feasibility Studies , Humans , Microcirculation , Oxygen Saturation , Perfusion , Prospective StudiesABSTRACT
The spread of severe acute respiratory syndrome coronavirus 2 began later in Africa than in Asia and Europe. Senegal confirmed its first case of coronavirus disease on March 2, 2020. By March 4, a total of 4 cases had been confirmed, all in patients who traveled from Europe.
Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Disease Transmission, Infectious/statistics & numerical data , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19 , Child , Child, Preschool , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS-CoV-2 , Senegal/epidemiology , Young AdultABSTRACT
During 2015-2016, Cape Verde, an island nation off the coast of West Africa, experienced a Zika virus (ZIKV) outbreak involving 7,580 suspected Zika cases and 18 microcephaly cases. Analysis of the complete genomes of 3 ZIKV isolates from the outbreak indicated the strain was of the Asian (not African) lineage. The Cape Verde ZIKV sequences formed a distinct monophylogenetic group and possessed 1-2 (T659A, I756V) unique amino acid changes in the envelope protein. Phylogeographic and serologic evidence support earlier introduction of this lineage into Cape Verde, possibly from northeast Brazil, between June 2014 and August 2015, suggesting cryptic circulation of the virus before the initial wave of cases were detected in October 2015. These findings underscore the utility of genomic-scale epidemiology for outbreak investigations.
Subject(s)
Microcephaly , Zika Virus Infection , Zika Virus , Africa, Western , Brazil/epidemiology , Cabo Verde , Disease Outbreaks , Genomics , Humans , Microcephaly/epidemiology , Zika Virus/genetics , Zika Virus Infection/epidemiologyABSTRACT
The era of genome-wide association studies (GWAS) has led to the discovery of numerous genetic variants associated with disease. Better understanding of whether these or other variants interact leading to differential risk compared with individual marker effects will increase our understanding of the genetic architecture of disease, which may be investigated using the family-based study design. We present M-TDT (the multi-locus transmission disequilibrium test), a tool for detecting family-based multi-locus multi-allelic effects for qualitative or quantitative traits, extended from the original transmission disequilibrium test (TDT). Tests to handle the comparison between additive and epistatic models, lack of independence between markers and multiple offspring are described. Performance of M-TDT is compared with a multifactor dimensionality reduction (MDR) approach designed for investigating families in the hypothesis-free genome-wide setting (the multifactor dimensionality reduction pedigree disequilibrium test, MDR-PDT). Other methods derived from the TDT or MDR to investigate genetic interaction in the family-based design are also discussed. The case of three independent biallelic loci is illustrated using simulations for one- to three-locus alternative hypotheses. M-TDT identified joint-locus effects and distinguished effectively between additive and epistatic models. We showed a practical example of M-TDT based on three genes already known to be implicated in malaria susceptibility. Our findings demonstrate the value of M-TDT in a hypothesis-driven context to test for multi-way epistasis underlying common disease etiology, whereas MDR-PDT-based methods are more appropriate in a hypothesis-free genome-wide setting.
Subject(s)
Epistasis, Genetic , Genome , Genome-Wide Association Study , Humans , Linkage Disequilibrium , Models, Genetic , PedigreeABSTRACT
BACKGROUND: Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO2) monitors. METHODS: Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6-8 h of daily monitoring. Brain PbO2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO2 below 19 mmHg for more than 6 min from baseline (PbO2 > 21 mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of "normal" (> 21 mmHg) and "low" (< 19 mmHg) PbO2. Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension. RESULTS: Seven patients were enrolled and monitored for a total of 17 days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO2, we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO2 epochs (AUC 0.876). CONCLUSIONS: The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy.
Subject(s)
Arterial Pressure/physiology , Cerebrovascular Circulation/physiology , Hypoxia-Ischemia, Brain/diagnostic imaging , Hypoxia-Ischemia, Brain/physiopathology , Neurophysiological Monitoring/methods , Adult , Brain Injuries/diagnostic imaging , Brain Injuries/physiopathology , Coma/diagnostic imaging , Coma/physiopathology , Female , Humans , Male , Middle Aged , Neuroimaging/methods , Neuroimaging/standards , Neurophysiological Monitoring/standards , Optical Imaging/methods , Optical Imaging/standards , Spectroscopy, Near-Infrared/methods , Spectroscopy, Near-Infrared/standardsABSTRACT
Given the projected growth of methane emission by ruminants in developing countries, there is a clear need for reliable estimates of their contribution to greenhouse gas emissions. Existing studies have rarely considered sheep and goats. The objective of this study was to predict enteric fermentation methane emission factors (EFs) for Djallonké sheep and West African Dwarf goats, following the 2006 IPCC Tier 2 methodology. Estimated enteric methane emission factors, expressed per head of animal per year, were 2.3 kg CH4 and 2.0 kg CH4 for sheep and goats species, respectively. Compared with the generic Tier 1 emission factor of 5 kg CH4 head proposed by the IPCC for small ruminants in the sub-Saharan Africa region, our suggested values are 56% and 60% lower for sheep and goat, respectively. These lower values took account of the particular flock structure of both sheep and goats. These estimates also accounted for differences in live weight according to age and corresponding estimated feed intake. This work is a step forward in the revision of small ruminant emission factors and can further support assessment of mitigation strategies in Senegalese livestock farming systems.
Subject(s)
Air Pollutants/analysis , Goats/metabolism , Methane/analysis , Sheep, Domestic/metabolism , Stomach/physiology , Animals , Female , Fermentation , Male , SenegalABSTRACT
BACKGROUND: Certain cancer case ascertainment methods used in Quebec and elsewhere are known to underestimate the burden of cancer, particularly for some subgroups. Algorithms using claims data are a low-cost option to improve the quality of cancer surveillance, but have not frequently been implemented at the population-level. Our objectives were to 1) develop a colorectal cancer (CRC) case ascertainment algorithm using population-level hospitalization and physician billing data, 2) validate the algorithm, and 3) describe the characteristics of cases. METHODS: We linked physician billing, hospitalization, and tumor registry data for 2,013,430 Montreal residents age 20+ (2000-2010). We compared the performance of three algorithms based on diagnosis and treatment codes from different data sources. We described identified cases according to age, sex, socioeconomic status, treatment patterns, site distribution, and time trends. All statistical tests were two-sided. RESULTS: Our algorithm based on diagnosis and treatment codes identified 11,476 of the 12,933 incident CRC cases contained in the tumor registry as well as 2317 newly-captured cases. Our cases share similar overall time trends and site distributions to existing data, which increases our confidence in the algorithm. Our algorithm captured proportionally 35% more individuals age 50 and younger among CRC cases: 8.2% vs. 5.3%. The newly captured cases were also more likely to be living in socioeconomically advantaged areas. CONCLUSIONS: Our algorithm provides a more complete picture of population-wide CRC incidence than existing case ascertainment methods. It could be used to estimate long-term incidence trends, aid in timely surveillance, and to inform interventions, in both Quebec and other jurisdictions.