This paper proposes and analyses a stochastic model for the spread of an infectious disease transmitted between clients and care workers in the UK domiciliary (home) care setting. Interactions between clients and care workers are modelled using specially generated networks, with network parameters reflecting realistic patterns of care needs and visit allocation. These networks are then used to simulate a susceptible-exposed-infected-recovered/dead (SEIR/D)-type epidemic dynamics with different numbers of infectious and recovery stages. The results indicate that with the same overall capacity provided by care workers, the minimum peak proportion of infection and the smallest overall size of infection are achieved for the highest proportion of overlap between visit allocation, i.e. when care workers have the highest chances of being allocated a visit to the same client they have visited before. An intuitive explanation of this is that while providing the required care coverage, maximising overlap in visit allocation reduces the possibility of an infectious care worker inadvertently spreading the infection to other clients. The model is generic and can be adapted to any directly transmitted infectious disease, such as, more recently, corona virus disease 2019, provided accurate estimates of disease parameters can be obtained from real data.

El Niño cave, located on the south-eastern border of the Spanish Meseta, hosts a discontinuous sequence including Middle Palaeolithic and Neolithic levels, along with Upper Palaeolithic and Levantine style paintings. It is a key site for understanding human occupations of inland Iberia during the Palaeolithic and early prehistory. This paper summarises the main results of a multidisciplinary project aimed at defining the prehistoric human occupations at the site.

Coxiella burnetii is a zoonotic agent responsible for human Q fever, a potentially severe disease that can lead to persistent infection. This cross-sectional study aimed to estimate the seroprevalence to C. burnetii antibodies and its association with potential risk factors in the human population of five regions of Québec, Canada. A serum bank comprising sera from 474 dog owners was screened by an enzyme-linked immunosorbent assay followed by confirmation of positive or equivocal sera by an indirect immunofluorescence assay. Observed seroprevalences of 1.2% (95% confidence interval (CI): 0.0–6.6), 2.6% (95% CI: 0.5–7.4) and 5.9% (95% CI: 3.4–9.6) were estimated in the regions of Montréal, Lanaudière and Montérégie, respectively, which all included at least 83 samples. Having lived or worked on a small ruminant farm (prevalence odds ratio (POR) = 5.4; 95% CI: 1.6–17.7) and being a veterinarian or veterinary student (POR = 6.1; 95% CI: 1.6–24.0) were significantly associated with C. burnetii seropositivity. Antibodies against C. burnetii were detected in the human population of Québec. Although seropositivity to this agent was associated with occupational contact with domestic animals, antibodies were also detected in people with no reported professional exposure. No associations with ruminant farm proximity were identified.

Dating of ancient permafrost is essential for understanding long-term permafrost stability and interpreting palaeoenvironmental conditions but presents substantial challenges to geochronology. Here, we apply four methods to permafrost from the megaslump at Batagay, east Siberia: (1) optically stimulated luminescence (OSL) dating of quartz, (2) post-infrared infrared-stimulated luminescence (pIRIR) dating of K-feldspar, (3) radiocarbon dating of organic material, and (4) 36Cl/Cl dating of ice wedges. All four chronometers produce stratigraphically consistent and comparable ages. However, OSL appears to date Marine Isotope Stage (MIS) 3 to MIS 2 deposits more reliably than pIRIR, whereas the latter is more consistent with 36Cl/Cl ages for older deposits. The lower ice complex developed at least 650 ka, potentially during MIS 16, and represents the oldest dated permafrost in western Beringia and the second-oldest known ice in the Northern Hemisphere. It has survived multiple interglaciations, including the super-interglaciation MIS 11c, though a thaw unconformity and erosional surface indicate at least one episode of permafrost thaw and erosion occurred sometime between MIS 16 and 6. The upper ice complex formed from at least 60 to 30 ka during late MIS 4 to 3. The sand unit above the upper ice complex is dated to MIS 3–2, whereas the sand unit below formed at some time between MIS 4 and 16.

The Ethiopian government has several initiatives to expand and intensify the dairy industry; however, the risk of bovine tuberculosis (bTB) spread is a challenge. To assess the rate of expansion and risk factors for transmission of bTB within-herds, we carried out a repeated cross-sectional survey at two time points, 2016/17 and 2018, in three regional cities, namely, Gondar, Hawassa and Mekelle, representing the emerging dairy belts of Ethiopia. The total number of herds involved was 128, comprising an average of 2303 cattle in each round. The Single Intradermal Comparative Cervical Tuberculin (SICCT) test was used to identify reactor status and data on herd-level risk factors were collected using a structured questionnaire. In the first survey, the apparent prevalence of bTB, as measured by the SICCT test, was 4.5% (95% CI 3.7–5.4%) at the individual animal-level and 24% (95% CI 17.5–32%) at the herd-level. There was no statistically significant change in the overall apparent prevalence or regional distribution at the second survey, consistent with the infection being endemic. The incidence rate was estimated at 3.6 (95% CI 2.8–4.5) and 6.6 (95% CI 3.0–12.6) cases/100 cattle (or herd)-years at the animal- and herd-levels, respectively. Risk factors significantly associated with the within-herd transmission of bTB were age group and within-herd apparent prevalence at the start of the observation period. We noted that farmers voluntarily took steps to remove reactor cattle from their herds as a consequence of the information shared after the first survey. Removal of reactors between surveys was associated with a reduced risk of transmission within these herds. However, with no regulatory barriers to the sale of reactor animals, such actions could potentially lead to further spread between herds. We therefore advocate the importance of setting up regulations and then establishing a systematic bTB surveillance programme to monitor the impact prior to implementing any control measures in Ethiopia.

Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.

Palmer amaranth, an annual weed, and Verticillium dahliae, a fungal pathogen, can substantially reduce chile pepper yield. On the basis of the results of this study, we clarified implementation strategies for a potential management tactic for Palmer amaranth and V. dahliae in chile pepper: mustard seed meal (MSM). The objectives were to (1) determine MSM effects on Palmer amaranth seedbanks under different moisture levels, (2) measure glucosinolate degradation in soil hydrated to saturation and field capacity, and (3) determine the effects of decreasing moisture availability on MSM control of Palmer amaranth and V. dahliae. To address objective 1, seedbanks with and without MSM were hydrated to levels expected to both inhibit and promote germination (flooded, saturated, −0.03, −0.6 MPa, respectively). For objective 2, soil columns with MSM were held at different moisture levels and sampled over time. For objective 3, Palmer amaranth seeds were incubated with and without MSM, and with polyethylene glycol (PEG) solutions comprising a range of water potentials (0, −0.03, −0.6, −1.0, and −2.0 MPa). These PEG solutions were also used to hydrate MSM in agar plates with plugs of V. dahliae. All experiments were performed in growth chambers with temperatures and light conditions conducive to Palmer amaranth germination and V. dahliae mycelial growth. MSM-induced mortality in Palmer amaranth seedbanks was greater in soil at field capacity than in saturated soil and flooded soil; however, rates of glucosinolate degradation were greatest in saturated soil. Decreasing water availability progressively decreased the efficacy of MSM on Palmer amaranth because MSM was ineffective on nongerminated seeds. When incubated with PEG solutions with water potentials of 0, −0.03, and −0.6 MPa, MSM stopped growth of V. dahliae; however, MSM-induced control of V. dahliae was reduced by water potentials of −1.0 and −2.0 MPa. The results of this study indicate soils hydrated to field capacity maximize MSM-induced control of Palmer amaranth and V. dahliae.

Environmental information from place-names has largely been overlooked by geoarchaeologists and fluvial geomorphologists in analyses of the depositional histories of rivers and floodplains. Here, new flood chronologies for the rivers Teme, Severn, and Wye are presented, modelled from stable river sections excavated at Broadwas, Buildwas, and Rotherwas. These are connected by the Old English term *wæsse, interpreted as ‘land by a meandering river which floods and drains quickly’. The results reveal that, in all three places, flooding during the early medieval period occurred more frequently between AD 350–700 than between AD 700–1100, but that over time each river's flooding regime became more complex including high magnitude single events. In the sampled locations, the fluvial dynamics of localized flood events had much in common, and almost certainly differed in nature from other sections of their rivers, refining our understanding of the precise nature of flooding which their names sought to communicate. This study shows how the toponymic record can be helpful in the long-term reconstruction of historic river activity and for our understanding of past human perceptions of riverine environments.

Although the process of hydrodynamic dispersion has been studied for many years, the description of solute spreading at early times has proved to be challenging. In particular, for some kinds of initial conditions, the solute evolution may exhibit a second moment that decreases (rather than increases, as is typically observed) in time. Most classical approaches would predict a negative effective hydrodynamic dispersion coefficient for such a situation. This creates some difficulties: not only does a negative dispersion coefficient lead to a violation of the second law of thermodynamics, but it also creates a mathematically ill-posed problem. We outline a set of four desirable qualities in a well-structured theory of unsteady dispersion as follows: (i) positivity of the dispersion coefficient, (ii) non-dependence upon initial conditions, (iii) superposability of solutions and (iv) convergence of solutions to classical asymptotic results. We use averaging to develop an upscaled result that adheres to these qualities. We find that the upscaled equation contains a source term that accounts for the relaxation of the initial configuration. This term decreases exponentially fast in time, leading to correct asymptotic behaviour while also accounting for the early-time solute dynamics. Analytical solutions are presented for both the effective dispersion coefficient and the source term, and we compare our upscaled results with averaged solutions obtained from numerical simulations; both averaged concentrations and spatial moments are compared. Error estimates are quantified, and we find good correspondence between the upscaled theory and the numerical results for all times.

Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.

Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.

A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.

A systematic review and meta-analysis were conducted to determine the efficacy of selective dry-cow antimicrobial therapy compared to blanket therapy (all quarters/all cows). Controlled trials were eligible if any of the following were assessed: incidence of clinical mastitis during the first 30 DIM, frequency of intramammary infection (IMI) at calving, or frequency of IMI during the first 30 DIM. From 3480 identified records, nine trials were data extracted for IMI at calving. There was an insufficient number of trials to conduct meta-analysis for the other outcomes. Risk of IMI at calving in selectively treated cows was higher than blanket therapy (RR = 1.34, 95% CI = 1.13, 1.16), but substantial heterogeneity was present (I2 = 58%). Subgroup analysis showed that, for trials using internal teat sealants, there was no difference in IMI risk at calving between groups, and no heterogeneity was present. For trials not using internal teat sealants, there was an increased risk in cows assigned to a selective dry-cow therapy protocol, compared to blanket treatment, with substantial heterogeneity in this subgroup. However, the small number of trials and heterogeneity in the subgroup without internal teat sealants suggests that the relative risk between treatments may differ from the determined point estimates based on other unmeasured factors.

A systematic review and network meta-analysis were conducted to assess the relative efficacy of antimicrobial therapy given to dairy cows at dry-off. Eligible studies were controlled trials assessing the use of antimicrobials compared to no treatment or an alternative treatment, and assessed one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, incidence of IMI during the first 30 days in milk (DIM), or incidence of clinical mastitis during the first 30 DIM. Databases and conference proceedings were searched for relevant articles. The potential for bias was assessed using the Cochrane Risk of Bias 2.0 algorithm. From 3480 initially identified records, 45 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. The use of cephalosporins, cloxacillin, or penicillin with aminoglycoside significantly reduced the risk of new IMI at calving compared to non-treated controls (cephalosporins, RR = 0.37, 95% CI 0.23–0.65; cloxacillin, RR = 0.55, 95% CI 0.38–0.79; penicillin with aminoglycoside, RR = 0.42, 95% CI 0.26–0.72). Synthesis revealed challenges with a comparability of outcomes, replication of interventions, definitions of outcomes, and quality of reporting. The use of reporting guidelines, replication among interventions, and standardization of outcome definitions would increase the utility of primary research in this area.