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\"The hoard of Roman-British temple treasure discovered at Ashwell in 2002 has provided fascinating new insight into the ritual of Roman religion both in Roman Britain and the wider Roman world.0First full publication of the Ashwell treasure since its high profile discovery in 2002. Features a detailed, highly illustrated discussion of the beautiful gold and silver votive plaques as well as the figurine of the previously unknown goddess Senuna.\"-- Back cover.

The cerebral cortex is a cellularly complex structure comprising a rich diversity of neuronal and glial cell types. Cortical neurons can be broadly categorized into two classes—excitatory neurons that use the neurotransmitter glutamate, and inhibitory interneurons that use γ-aminobutyric acid (GABA). Previous developmental studies in rodents have led to a prevailing model in which excitatory neurons are born from progenitors located in the cortex, whereas cortical interneurons are born from a separate population of progenitors located outside the developing cortex in the ganglionic eminences 1 – 5 . However, the developmental potential of human cortical progenitors has not been thoroughly explored. Here we show that, in addition to excitatory neurons and glia, human cortical progenitors are also capable of producing GABAergic neurons with the transcriptional characteristics and morphologies of cortical interneurons. By developing a cellular barcoding tool called ‘single-cell-RNA-sequencing-compatible tracer for identifying clonal relationships’ (STICR), we were able to carry out clonal lineage tracing of 1,912 primary human cortical progenitors from six specimens, and to capture both the transcriptional identities and the clonal relationships of their progeny. A subpopulation of cortically born GABAergic neurons was transcriptionally similar to cortical interneurons born from the caudal ganglionic eminence, and these cells were frequently related to excitatory neurons and glia. Our results show that individual human cortical progenitors can generate both excitatory neurons and cortical interneurons, providing a new framework for understanding the origins of neuronal diversity in the human cortex. Molecular barcoding is used to show that progenitor cells in the human cortex can produce both excitatory neurons and inhibitory interneurons, with implications for our understanding of the evolution of the human brain.

Outbreak response efforts for the 2014–15 Ebola virus disease epidemic in west Africa brought widespread transmission to an end. However, subsequent clusters of infection have occurred in the region. An Ebola virus disease cluster in Liberia in November, 2015, that was identified after a 15-year-old boy tested positive for Ebola virus infection in Monrovia, raised the possibility of transmission from a persistently infected individual. Case investigations were done to ascertain previous contact with cases of Ebola virus disease or infection with Ebola virus. Molecular investigations on blood samples explored a potential linkage between Ebola virus isolated from cases in this November, 2015, cluster and epidemiologically linked cases from the 2014–15 west African outbreak, according to the national case database. The cluster investigated was the family of the index case (mother, father, three siblings). Ebola virus genomes assembled from two cases in the November, 2015, cluster, and an epidemiologically linked Ebola virus disease case in July, 2014, were phylogenetically related within the LB5 sublineage that circulated in Liberia starting around August, 2014. Partial genomes from two additional individuals, one from each cluster, were also consistent with placement in the LB5 sublineage. Sequencing data indicate infection with a lineage of the virus from a former transmission chain in the country. Based on serology and epidemiological and genomic data, the most plausible scenario is that a female case in the November, 2015, cluster survived Ebola virus disease in 2014, had viral persistence or recurrent disease, and transmitted the virus to three family members a year later. Investigation of the source of infection for the November, 2015, cluster provides evidence of Ebola virus persistence and highlights the risk for outbreaks after interruption of active transmission. These findings underscore the need for focused prevention efforts among survivors and sustained capacity to rapidly detect and respond to new Ebola virus disease cases to prevent recurrence of a widespread outbreak. US Centers for Disease Control and Prevention, Defense Threat Reduction Agency, and WHO.

Maternal, fetal, and neonatal health outcomes are interdependent. Designing public health strategies that link fetal and neonatal outcomes with maternal outcomes is necessary in order to successfully reduce perinatal and neonatal mortality, particularly in low- and middle- income countries. However, to date, there has been no standardized method for documenting, reporting, and reviewing facility-based stillbirths and neonatal deaths that links to maternal health outcomes would enable a more comprehensive understanding of the burden and determinants of poor fetal and neonatal outcomes. We developed and pilot-tested an adapted RAPID tool, Perinatal-Neonatal Rapid Ascertainment Process for Institutional Deaths (PN RAPID), to systematically identify and quantify facility-based stillbirths and neonatal deaths and link them to maternal health factors in two countries: Liberia and Nepal. This study found an absence of stillbirth timing documented in records, a high proportion of neonatal deaths occurring within the first 24 hours, and an absence of documentation of pregnancy-related and maternal factors that might be associated with fetal and neonatal outcomes. The use of an adapted RAPID methodology and tools was limited by these data gaps, highlighting the need for concurrent strengthening of death documentation through training and standardized record templates.

ObjectivesThe overuse of antimalarial drugs is widespread. Effective methods to improve prescribing practice remain unclear. We evaluated the impact of 10 interventions that introduced rapid diagnostic tests for malaria (mRDTs) on the use of tests and adherence to results in different contexts.DesignA comparative case study approach, analysing variation in outcomes across different settings.SettingStudies from the ACT Consortium evaluating mRDTs with a range of supporting interventions in 6 malaria endemic countries. Providers were governmental or non-governmental healthcare workers, private retail sector workers or community volunteers. Each study arm in a distinct setting was considered a case.Participants28 cases from 10 studies were included, representing 148 461 patients seeking care for suspected malaria.InterventionsThe interventions included different mRDT training packages, supervision, supplies and community sensitisation.Outcome measuresAnalysis explored variation in: (1) uptake of mRDTs (% febrile patients tested); (2) provider adherence to positive mRDTs (% Plasmodium falciparum positive prescribed/given Artemisinin Combination Treatment); (3) provider adherence to negative mRDTs (% P. falciparum negative not prescribed/given antimalarial).ResultsOutcomes varied widely across cases: 12–100% mRDT uptake; 44–98% adherence to positive mRDTs; 27–100% adherence to negative mRDTs. Providers appeared more motivated to perform well when mRDTs and intervention characteristics fitted with their own priorities. Goodness of fit of mRDTs with existing consultation and diagnostic practices appeared crucial to maximising the impact of mRDTs on care, as did prior familiarity with malaria testing; adequate human resources and supplies; possible alternative treatments for mRDT-negative patients; a more directive intervention approach and local preferences for ACTs.ConclusionsBasic training and resources are essential but insufficient to maximise the potential of mRDTs in many contexts. Programme design should respond to assessments of provider priorities, expectations and capacities. As mRDTs become established, the intensity of supporting interventions required seems likely to reduce.

Fever is a common symptom of infectious diseases including for those with epidemic potential. Beyond malaria, the causes of undifferentiated (i.e., non-respiratory, non-diarrheal) acute febrile illnesses are not well characterized in Liberia. From December 2018 through March 2020, we established two acute febrile illness (AFI) sentinel surveillance sites in urban Monrovia at Redemption Hospital and Star of the Sea Health Centre, health facilities that were among the first to have Ebola cases during the 2014-2015 West Africa epidemic. Enrolled AFI patients were two (2) years of age or greater, had a measured fever of ≥37.5oC or history of fever within the past week, and without a known cause of fever. A standardized survey was administered to collect demographic, clinical characteristics, and risk factors. Whole blood was taken, nucleic acid material was extracted and ran on TaqMan Array Cards (TAC), a real-time polymerase chain reaction (RT-PCR) testing platform for 28 pathogens. Data were analyzed using descriptive statistics, and multivariate regression models of any TAC detections stratified by site and age. We enrolled 1506 AFI patients, 1206 (80%) from Redemption Hospital and 300 (20%) from Star of the Sea. AFI patients were predominantly female (69%) and had a median (interquartile range) age of 18 (7-27) years. Among the 699 (46%) that were TAC positive, 627 were detected from Redemption Hospital and 72 were detected from Star of the Sea Health Centre. Overall Plasmodium spp. (malaria) (96%) were the majority of detections followed by dengue virus (2%), Streptococcus pneumoniae (2%), and Rickettsia spp. (1%). We detected 19 co-infections [malaria co-infections (84%) being the most common]. Two pathogens with epidemic potential, Neisseria meningitidis (detected at Star of the Sea Health Centre) and Lassa virus (detected at Redemption Hospital), were also found. Patients with non-malaria TAC detections (n = 29) were higher at Star of the Sea Health Centre than Redemption Hospital (4% versus 1% respectively, p < 0.05). In multivariate regression for those ages 15 years and older at Redemption Hospital (adjusting for sex, age, pregnancy status, education, occupation, any medication use, measured fever at enrollment, headache, abdominal pain, vomiting/nausea and joint pain), any medication use (aOR=0.6, 95% CI = 0.4-0.9), measured fever at enrollment (aOR=3.5, 95% CI = 1.1-12.0), headache (aOR=1.7, 95% CI = 1.1-2.6 were statistically significant with any TAC detection. In multivariate regression for those ages 2-14 years at Redemption Hospital (adjusting for sex, age, abdominal pain, cough, vomiting/nausea, runny nose, and any animal exposure), having abdominal pain (aOR=1.9, 95% CI = 1.3-2.8), vomiting/nausea (aOR=0.6, 95% CI = 0.4-1.0), and any animal exposure (aOR=1.5, 95% CI = 1.0-2.3) were statistically significant with any TAC detection. This is the first laboratory evidence of dengue and rickettsial disease in humans in Liberia. Liberia's incipient AFI platform was successful exploring causes of fever in emerging infections and detected circulating pathogens beyond malaria. AFI surveillance data can assist in the prioritization of public health diagnostic and clinical capabilities to prevent, detect, and respond to emerging infectious disease threats in Liberia.

Reelin is a regulator of cell migration in the nervous system, and has other functions in the development of a number of non-neuronal tissues. In addition, alterations in reelin expression levels have been reported in breast, pancreatic, liver, gastric, and other cancers. Reelin is normally expressed in mammary gland stromal cells, but whether stromal reelin contributes to breast cancer progression is unknown. Herein, we used a syngeneic mouse mammary tumor transplantation model to examine the impact of host-derived reelin on breast cancer progression. We found that transplanted syngeneic tumors grew more slowly in reelin-deficient (rlOrl −/−) mice and had delayed metastatic colonization of the lungs. Immunohistochemistry of primary tumors revealed that tumors grown in rlOrl −/− animals had fewer blood vessels and increased macrophage infiltration. Gene expression studies from tumor tissues indicate that loss of host-derived reelin alters the balance of M1- and M2-associated macrophage markers, suggesting that reelin may influence the polarization of these cells. Consistent with this, rlOrl −/− M1-polarized bone marrow-derived macrophages have heightened levels of the M1-associated cytokines iNOS and IL-6. Based on these observations, we propose a novel function for the reelin protein in breast cancer progression.

Little empirical evidence suggested that independent reading abilities of students enrolled in biology predicted their performance on the Biology I Graduation End-of-Course Assessment (ECA). An archival study was conducted at one Indiana urban public high school in Indianapolis, Indiana, by examining existing educational assessment data to test whether a relationship between reading proficiency and student performance on the Biology I ECA existed. The Pearson product-moment correlation coefficient was r = 0.712 (P < 0.01). A strong positive relationship between Biology I ECA and Lexile reading scores accounted for 50.7% of the variance. The results suggested that any measure to increase reading levels would increase standardized biology assessment scores.

Background Intermittent mass screening and treatment (iMSaT) is currently being evaluated as a possible additional tool for malaria control and prevention in western Kenya. The literature identifying success and/or barriers to drug trial compliance and acceptability on malaria treatment and control interventions is considerable, especially as it relates to specific target groups, such as school-aged children and pregnant women, but there is a lack of such studies for mass screening and treatment and mass drug administration in the general population. Methods A qualitative study was conducted to explore community perceptions of the iMSaT intervention, and specifically of testing and treatment in the absence of symptoms, before and after implementation in order to identify aspects of iMSaT that should be improved in future rounds. Two rounds of qualitative data collection were completed in six randomly selected study communities: a total of 36 focus group discussions (FGDs) with men, women, and opinion leaders, and 12 individual or small group interviews with community health workers. All interviews were conducted in the local dialect Dholuo, digitally recorded, and transcribed into English. English transcripts were imported into the qualitative software programme NVivo8 for content analysis. Results There were mixed opinions of the intervention. In the pre-implementation round, respondents were generally positive and willing to participate in the upcoming study. However, there were concerns about testing in the absence of symptoms including fear of covert HIV testing and issues around blood sampling. There were fewer concerns about treatment, mostly because of the simpler dosing regimen of the study drug (dihydroartemisinin–piperaquine) compared to the current first-line treatment (artemether–lumefantrine). After the first implementation round, there was a clear shift in perceptions with less common concerns overall, although some of the same issues around testing and general misconceptions about research remained. Conclusions Although iMSaT was generally accepted throughout the community, proper sensitization activities—and arguably, a more long-term approach to community engagement—are necessary for dispelling fears, clarifying misconceptions, and educating communities on the consequences of asymptomatic malaria.

The National Human Immunodeficiency Virus (HIV) Behavioral Surveillance System (NHBS) is the Centers for Disease Control and Prevention's (CDC's) newest system for measuring HIV risk behaviors among three adult populations at highest risk for HIV infection in the U.S.: men who have sex with men, injecting drug users, and heterosexuals at risk of HIV infection. The system is implemented by state and local health departments in designated metropolitan statistical areas with the highest HIV/acquired immunodeficiency syndrome (AIDS) prevalence in the U.S. Prior to implementing the behavioral surveillance survey, project sites conduct a series of formative research activities. The data collected during this preparatory phase provide contextual information about HIV risk behaviors within the study population of interest and help project sites make decisions about field operations and other logistical issues. This article describes the activities undertaken in preparation for the first round of NHBS (2003–2007) and how those activities enhanced data collection for each behavioral surveillance cycle.