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High throughput technologies in genomics enable the analysis of small alterations in gene expression levels. Patterns of such deviations are an important starting point for the discovery and verification of new biomarker candidates. Identifying such patterns is a challenging task that requires sophisticated machine learning approaches. Currently, there are a variety of classification models, and a common approach is to compare the performance and select the best one for a given classification problem. Since the association between the features of a data set and the performance of a particular classification method is still not fully understood, the main contribution of this work is to provide a new methodology for predicting the prediction results of different classifiers in the field of biomarker discovery. We propose here a three-steps computational workflow that includes an analysis of the data set characteristics, the calculation of the classification accuracy and, finally, the prediction of the resulting classification error. The experiments were carried out on synthetic and microarray datasets. Using this method, we showed that the predictability strongly depends on the discriminatory ability of the features, e.g., sets of genes, in two or multi-class datasets. If a dataset has a certain discriminatory ability, this method enables prediction of the classification performance before applying a learning model. Thus, our results contribute to a better understanding of the relationship between dataset characteristics and the corresponding performance of a machine learning method, and suggest the optimal classification method for a given dataset based on its discriminatory ability.

Background Older adults with chronic conditions are at high risk of complications from influenza and pneumococcal infections. Evidence about factors associated with influenza and pneumococcal vaccination among older multimorbid persons in Europe is limited. The aim of this study was to investigate the prevalence and determinants of these vaccinations in this population. Methods Multimorbid patients aged ≥70 years with polypharmacy were enrolled in 4 European centers in Switzerland, Belgium, the Netherlands, and Ireland. Data on vaccinations, demographics, health care contacts, and comorbidities were obtained from self-report, general practitioners and medical records. The association of comorbidities or medical contacts with vaccination status was assessed using multivariable adjusted log-binomial regression models. Results Among 1956 participants with available influenza vaccination data (median age 79 years, 45% women), 1314 (67%) received an influenza vaccination within the last year. Of 1400 patients with available pneumococcal vaccination data (median age 79 years, 46% women), prevalence of pneumococcal vaccination was 21% (n = 291). The prevalence of vaccination remained low in high-risk populations with chronic respiratory disease (34%) or diabetes (24%), but increased with an increasing number of outpatient medical contacts. Chronic respiratory disease was independently associated with the receipt of both influenza and pneumococcal vaccinations (prevalence ratio [PR] 1.09, 95% confidence interval [CI] 1.03–1.16; and PR 2.03, 95%CI 1.22–3.40, respectively), as was diabetes (PR 1.06, 95%CI 1.03–1.08; PR 1.24, 95%CI 1.16–1.34, respectively). An independent association was found between number of general practitioner visits and higher prevalence of pneumococcal vaccination (p for linear trend Conclusion Uptake of influenza and particularly of pneumococcal vaccination in this population of European multimorbid older inpatients remains insufficient and is determined by comorbidities and number and type of health care contacts, especially outpatient medical visits. Hospitalization may be an opportunity to promote vaccination, particularly targeting patients with few outpatient physician contacts.

BackgroundThailand was the first country outside China to report SARS-CoV-2 infected cases. Since the detection of the first imported case on January 12th, 2020 to the time this report was written, Thailand experienced two waves of community outbreaks (March-April 2020 and December 2020-March 2021). We examined prevalence of SARS-CoV-2 seropositivity among healthcare providers (HCPs) in four hospitals approximately one year after SARS-CoV-2 first detected in Thailand. By March 2021, these hospitals have treated a total of 709 coronavirus disease 2019 (COVID-19) patients.MethodsBlood specimens, collected from COVID-19 unvaccinated HCPs during January-March 2021, were tested for the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies to nucleocapsid (IgG-nucleocapsid) and spike (IgG-spike) proteins using Euroimmune®enzyme-linked immunosorbent assays.ResultsOf 600 HCPs enrolled, 1 (0.2%) tested positive for the SARS-CoV-2 IgG-spike antibodies, but not the IgG-nucleocapsid.ConclusionThe presence of SARS-CoV-2 IgG antibodies was rare in this sample of HCPs, suggesting that this population remains susceptible to SARS-CoV-2 infection.

This preliminary clinical investigation of the pharmacokinetic behavior of the main metamizole (dipyrone) metabolites 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA) in calves undergoing umbilical surgery is part of an already published main study. A single intravenous dose of metamizole was added to ketamine/xylazine/isoflurane anesthesia. Eight Simmental calves weighing 90 ± 10.8 kg and aged 47.6 ± 10.4 days received 40 mg/kg metamizole intravenously 10 minutes prior to general anesthesia. Blood samples were collected over 24 hours and analyzed for 4-MAA and 4-AA. Meloxicam was additionally given twice: 2.5 hours pre- and 20.5 hours postsurgically. The pharmacokinetic profile of 4-MAA was best fitted to a two-compartment model and was characterized by a fast distribution half-life and slow elimination half-life (t½alpha = 5.29 minutes, t½beta = 9.49 hours). The maximum concentration (Cmax 101.63 μg/mL) was detected at the first measurement time point 15 minutes after administration. In contrast, 4-AA showed fast, high and biphasic plasma peak concentration behavior in five calves (2.54–2.66 μg/mL after 15–30 minutes, and 2.10–2.14 μg/mL after 2–3.5 hours) with a t½beta of 8.87 hours, indicating a rapid distribution and subsequent redistribution from well-perfused organs. Alternatively, three calves exhibited a slower and lower monophasic plasma peak concentration (1.66 μg/mL after 6.5 hours) with a t½beta of 6.23 hours, indicating slow accumulation in the intravascular compartment. The maximum concentration and area under the plasma concentration curve (AUC) of 4-AA were lower than those of 4-MAA. This metabolic behavior supports our already published data on clinical monitoring and plasma cortisol concentrations (PCCs). Compared to those of saline controls, lower PCCs correspond to the t½alpha of 4-MAA. Data on Tmax and t½beta also match these clinical observations. However, further studies are required to assess the exact analgesic mechanism and potency of the metamizole metabolites in calves.

In many regions of sub Saharan Africa large mammals occur in human-dominated areas, yet their community composition and abundance have rarely been described in areas occupied by traditional hunter-gatherers and pastoralists. Surveys of mammal populations in such areas provide important measures of biodiversity and provide ecological context for understanding hunting practices. Using a sampling grid centered on a Hadza hunter-gatherer camp and covering 36 km2of semi-arid savannah in northern Tanzania, we assessed mammals using camera traps (n = 19 stations) for c. 5 months (2,182 trap nights). In the study area (Tli’ikain the Hadza language), we recorded 36 wild mammal species. Rarefaction curves suggest that sampling effort was sufficient to capture mammal species richness, yet some species known to occur at low densities in the wider area (e.g. African lions, wildebeest) were not detected. Relative abundance indices of wildlife species varied by c. three orders of magnitude, from a mean of 0.04 (African wild dog) to 20.34 capture events per 100 trap-nights (Kirk’s dik dik). To contextualize the relative abundance of wildlife in the study area, we compared our study’s data to comparable camera trap data collected in a fully protected area of northern Tanzania with similar rainfall (Lake Manyara National Park). Raw data and negative binomial regression analyses show that wild herbivores and wild carnivores were generally detected in the national park at higher rates than in the Hadza-occupied region. Livestock were notably absent from the national park, but were detected at high levels in Tli’ika, and cattle was the second most frequently detected species in the Hadza-used area. We discuss how these data inform current conservation efforts, studies of Hadza hunting, and models of hunter-gatherer foraging ecology and diet.

Corticotropin releasing factor (CRF) systems in limbic structures are posited to mediate stress-induced relapse in addiction, traditionally by generating distress states that spur drug consumption as attempts at hedonic self-medication. Yet evidence suggests that activating CRF-expressing neurons in the central amygdala (CeA) or nucleus accumbens (NAc) can magnify incentive motivation in absence of distress, at least for sucrose rewards. However, traditional CRF hypotheses in addiction neuroscience are primarily directed toward drug rewards. The question remains open whether CRF systems can similarly act via incentive motivation mechanisms to promote pursuit of drug rewards, such as cocaine. Here we tested whether optogenetic excitation of CRF-containing neurons in either NAc medial shell, lateral CeA, or dorsolateral BNST of transgenic Crh-Cre+ rats would spur preference and pursuit of a particular laser-paired cocaine reward over an alternative cocaine reward, and whether excitation served as a positively-valenced incentive itself, through laser self-stimulation tests. We report that excitation of CRF-containing neurons in either NAc or CeA recruited mesocorticolimbic circuitry to amplify incentive motivation to pursue the laser-paired cocaine: focusing preference on the laser-paired cocaine reward in a two-choice task, and spurred pursuit as doubled breakpoint in a progressive ratio task. Crucially indicating positive-valence, excitation of CRF neurons in NAc and CeA also was actively sought after by most rats in self-stimulation tasks. Conversely, CRF neuronal activation in BNST was never self-stimulated, but failed to enhance cocaine consumption. Collectively, we find that NAc and CeA CRF-containing neurons can amplify pursuit and consumption of cocaine by positively-valenced incentive mechanisms, without any aversive distress.

Background Monitoring COVID-19 infection risk among health care workers (HCWs) is a public health priority. We examined the seroprevalence of SARS-CoV-2 among HCWs following the fall infection surge in Minnesota, and before and after COVID-19 vaccination. Additionally, we assessed demographic and occupational risk factors for SARS-CoV-2 infection. Methods We conducted two rounds of seroprevalence testing among a cohort of HCWs: samples in round 1 were collected from 11/22/20–02/21/21 and in round 2 from 12/18/20–02/15/21. Demographic and occupational exposures assessed with logistic regression were age, sex, healthcare role and setting, and number of children in the household. The primary outcome was SARS-CoV-2 IgG seropositivity. A secondary outcome, SARS-CoV-2 infection, included both seropositivity and self-reported SARS-CoV-2 test positivity. Results In total, 459 HCWs were tested. 43/454 (9.47%) had a seropositive sample 1 and 75/423 (17.7%) had a seropositive sample 2. By time of sample 2 collection, 54% of participants had received at least one vaccine dose and seroprevalence was 13% among unvaccinated individuals. Relative to physicians, the odds of SARS-CoV-2 infection in other roles were increased (Nurse Practitioner: OR[95%CI] 1.93[0.57,6.53], Physician’s Assistant: 1.69[0.38,7.52], Nurse: 2.33[0.94,5.78], Paramedic/EMTs: 3.86[0.78,19.0], other: 1.68[0.58,4.85]). The workplace setting was associated with SARS-CoV-2 infection (p = 0.04). SARS-CoV-2 seroprevalence among HCWs reporting duties in the ICU vs. those working in an ambulatory clinic was elevated: OR[95%CI] 2.17[1.01,4.68]. Conclusions SARS-CoV-2 seroprevalence in HCW increased during our study period which was consistent with community infection rates. HCW role and setting—particularly working in the ICU—is associated with higher risk for SARS-CoV-2 infection.

Purpose Impairment of cognitive functions is commonly observed in temporal lobe epilepsy (TLE). The aim of this study was to assess visuospatial memory functions and memory-related networks using an adapted version of Roland’s Hometown Walking (RHWT) functional MRI (fMRI) task in patients with TLE. Methods We used fMRI to study activation patterns based on a visuospatial memory paradigm in 32 TLE patients (9 right; 23 left) and also within subgroups of lesional and non-lesional TLE. To test for performance, a correlational analysis of fMRI activation patterns and out-of-scanner neuropsychological visuospatial memory testing was performed. Additionally, we assessed memory-related networks using functional connectivity (FC). Results Greater contralateral than ipsilateral mesiotemporal (parahippocampal gyrus/hippocampus) activation was observed in left (n = 23)/right (n = 9) TLE. In lesional left TLE (n = 17), significant activations were seen in right more than left mesiotemporal areas (parahippocampal gyrus), while non-lesional left TLE patients (n = 6) showed significant bilateral (left>right) activations in mesiotemporal structures (parahippocampal gyrus). In left TLE, visuospatial cognitive testing correlated with fMRI activations in left (parahippocampal gyrus) and right mesiotemporal structures (hippocampus), characterized by greater fMRI activation being associated with better memory scores. In right TLE, higher scores in visuospatial memory testing were associated with greater fMRI activations in left and right insular regions. FC patterns of memory-related networks differ in right and left TLE. Conclusion While TLE in general leads to asymmetrical mesiotemporal activation, lesion-induced and non-lesional TLE patients reveal different memory fMRI activation patterns. In right TLE, insular regions try to compensate for impaired right mesiotemporal structures during the performance of visuospatial tasks. Underlying functional visuospatial memory networks differ in right and left TLE.

Tephritid fruit flies are among the most destructive horticultural pests posing risks to Australia's multi-billion-dollar horticulture industry. Currently, there are 11 pest fruit fly species of economic concern in Australia. Of these, nine are native to this continent (Bactrocera aquilonis, B. bryoniae, B. halfordiae, B. jarvisi, B. kraussi, B. musae, B. neohumeralis, B. tryoni and Zeugodacus cucumis), while B. frauenfeldi and Ceratitis capitata are introduced. To varying degrees these species are costly to Australia's horticulture through in-farm management, monitoring to demonstrate pest freedom, quarantine and trade restrictions, and crop losses. Here, we used a common species distribution model, Maxent, to assess climate suitability for these 11 species under baseline (1960-1990) and future climate scenarios for Australia. Projections indicate that the Wet Tropics is likely to be vulnerable to all 11 species until at least 2070, with the east coast of Australia also likely to remain vulnerable to multiple species. While the Cape York Peninsula and Northern Territory are projected to have suitable climate for numerous species, extrapolation to novel climates in these areas decreases confidence in model projections. The climate suitability of major horticulture areas currently in eastern Queensland, southern-central New South Wales and southern Victoria to these pests may increase as climate changes. By highlighting areas at risk of pest range expansion in the future our study may guide Australia's horticulture industry in developing effective monitoring and management strategies.

The Saving Lives at Birth (SL@B) funding partners joined in 2011 to source, support, and scale maternal and newborn health (MNH) innovations to improve maternal and newborn survival by focusing on the 24 hours around the time of birth. A multi-methods, retrospective portfolio evaluation was conducted to determine SL@B’s impact. Forty semi-structured, key informant interviews (KIIs) were conducted with experts in global MNH based in low- and middle-income and in high-income countries to assess the SL@B program. KIIs were conducted with global MNH technical experts, innovators, government officials in low- and middle-income countries, donors, private investors, and implementing partners to include the full spectrum of voices involved in identifying and scaling innovations. Data were analyzed using thematic analysis. Stakeholders believe the SL@B program has been successful in changing the way maternal and newborn health programs are delivered with a focus on doing things differently through innovation. The open approach to sourcing innovation was seen as positive to the extent that it brought more interdisciplinary stakeholders to think about the problem of maternal and newborn survival. However, a demand-driven approach that aims to source innovations that address MNH priority needs and takes into account the needs of end users (e.g. individuals and governments) was suggested as a strategy for ensuring that more innovations go to scale.

BackgroundThis research advances understanding of interrelationships among three barriers to adherence to antiretroviral therapy (ART) among pregnant women living with HIV (WLWH) in Cameroon: probable common mental disorders (CMD), intimate partner violence (IPV), and hunger.MethodsThe sample included 220 pregnant WLWH in Cameroon. Multivariable modified Poisson regression was conducted to assess the relationship between IPV, hunger, and CMD on ART adherence.ResultsAlmost half (44%) of participants recently missed/mistimed an ART dose. Probable CMD was associated with greater risk of missed/mistimed ART dose (aRR 1.5 [95% CI 1.1, 1.9]). Hunger was associated with greater risk of missed/mistimed ART dose among those who reported IPV (aRR 1.9 [95% CI 1.2, 2.8]), but not among those who did not (aRR 0.8 [95% CI 0.2, 2.3]).ConclusionSuboptimal ART adherence, CMD, and IPV were common among pregnant WLWH in Cameroon. Pregnant WLWH experiencing IPV and hunger may be especially vulnerable to suboptimal ART adherence.

BackgroundObstetric fistula significantly impacts women's mental health and well-being. Routine screening for mental health in fistula repair programs can be a gateway to link patients to services, and can produce routine data to inform programmatic investments. This study observed the integration of a mental health screening program into an obstetric fistula repair program in Mali, with two specific objectives: 1) to describe the social and mental health well-being of women presenting with obstetric fistulas in Mali, and 2) to document the impact of the mental health screening pilot on policy change in Mali.MethodsSeven fistula repair campaigns were conducted between June 2016 and May 2017. All individuals presenting for fistula repair completed a mental health assessment at intake, including a depression screener (PHQ-9) and an assessment of psycho-social impacts of fistula. The depression screener was repeated three months following inpatient discharge. Findings were shared with stakeholders in Mali and impacts on policy were documented.ResultsOf 207 women who presented for fistula repair, 167 patients completed the mental health assessment at surgical intake, and 130 patients repeated the screener at 3-month follow-up. At intake, 36.5% of women had moderate or severe depression, decreasing to 16.9% at follow-up. The mean depression score differed significantly by timepoint (9.14 vs. 6.72, p ConclusionThe high prevalence of depression in Malian fistula patients underscores a need for more robust mental health support for patients after surgery. Data on mental health from routine screening informs community reintegration strategies for individual patients, elevates the overall quality of care of fistula repair programs by addressing patients' holistic health needs, and contributes to evidence-informed decision-making and data-driven policy change within the larger health system.