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Microscopic examination of blood smears remains the gold standard for laboratory inspection and diagnosis of malaria. Smear inspection is, however, time-consuming and dependent on trained microscopists with results varying in accuracy. We sought to develop an automated image analysis method to improve accuracy and standardization of smear inspection that retains capacity for expert confirmation and image archiving. Here, we present a machine learning method that achieves red blood cell (RBC) detection, differentiation between infected/uninfected cells, and parasite life stage categorization from unprocessed, heterogeneous smear images. Based on a pretrained Faster Region-Based Convolutional Neural Networks (R-CNN) model for RBC detection, our model performs accurately, with an average precision of 0.99 at an intersection-over-union threshold of 0.5. Application of a residual neural network-50 model to infected cells also performs accurately, with an area under the receiver operating characteristic curve of 0.98. Finally, combining our method with a regression model successfully recapitulates intraerythrocytic developmental cycle with accurate lifecycle stage categorization. Combined with a mobile-friendly web-based interface, called PlasmoCount, our method permits rapid navigation through and review of results for quality assurance. By standardizing assessment of Giemsa smears, our method markedly improves inspection reproducibility and presents a realistic route to both routine lab and future field-based automated malaria diagnosis.
A survey of Veterans’ Affairs Medical Centers on control of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-producing CRE (CP-CRE) demonstrated that most facilities use VA guidelines but few screen for CRE/CP-CRE colonization regularly or regularly communicate CRE/CP-CRE status at patient transfer. Most respondents were knowledgeable about CRE guidelines but cited lack of adequate resources.
Social jetlag (SJ) occurs when sleep-timing irregularities from social or occupational demands conflict with endogenous sleep–wake rhythms. SJ is associated with evening chronotype and poor mental health, but mechanisms supporting this link remain unknown. Impaired ability to retrieve extinction memory is an emotion regulatory deficit observed in some psychiatric illnesses. Thus, SJ-dependent extinction memory deficits may provide a mechanism for poor mental health. To test this, healthy male college students completed 7–9 nights of actigraphy, sleep questionnaires, and a fear conditioning and extinction protocol. As expected, greater SJ, but not total sleep time discrepancy, was associated with poorer extinction memory. Unexpectedly, greater SJ was associated with a tendency toward morning rather than evening chronotype. These findings suggest that deficient extinction memory represents a potential mechanism linking SJ to psychopathology and that SJ is particularly problematic for college students with a greater tendency toward a morning chronotype.
A number of genomic conditions caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders (ND-CNVs). Although these patients also tend to have cognitive impairments, few studies have investigated the range of emotion and behaviour problems in young people with ND-CNVs using measures that are suitable for those with learning difficulties.
A total of 322 young people with 13 ND-CNVs across eight loci (mean age: 9.79 years, range: 6.02–17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC).
Of the total, 69% of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR = 0.71, CI = 0.55–0.91, p = .008) were less likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (χ2 = 39.99, p < 0.001), with the lowest rate in young people with 22q11.2 deletion (45.7%) and the highest in those with 1q21.1 deletion (93.8%). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 9–16% of the variance, depending on DBC subdomain.
Emotion and behaviour problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in emotion and behaviour problems not accounted for by genotype.
Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts.
To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes.
Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders.
In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being.
Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.
Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence.
To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence.
Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes.
13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender.
Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p < 0.05) but not OPRK1 gene. The rs2281285 - rs199794 haplotype showed significant association (p = 0.0236) with negative craving, while rs2235749 - rs10485703 haplotype showed marginally significant association (p = 0.055). This replicates previous findings of association between these haplotypes and alcohol dependence. Negative craving was also associated with PDYN rs2281285 variant (p = 0.012) with estimated effect size of 6.95 (SE = 2.75). This new association finding was not significant after correction for multiple testing (p = 0.18).
Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.
We recently identified association between GRIN2B rs2058878 variant and abstinence length in acamprosate-treated alcoholics (Karpyak et al. 2014). Here we present results of additional analyses exploring associations in the same sample (225 alcoholics treated with acamprosate for three months) at the gene and gene-set levels, for 12 genes involved in glycine signaling, 4 genes involved in glutamate reuptake, synthesis and degradation and 7 genes encoding NMDA receptor subunits.
After adjustment for relevant covariates, gene-level tests were performed using principal components (PC) analysis. Gene-set analyses were performed using the PC-Gamma approach with varying soft truncation threshold (STT) for the Gamma method for combining gene-level p-values.
Shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between last drink and initiation of acamprosate treatment. After adjustment for covariates, we observed nominally significant association of abstinence length with variation in the AMT (p=0.024), GRIN3A (p=0.016) and SHMT2 (p=0.039) genes, and marginally significant evidence for association with the GRIN2B (p=0.067) and GLRB (p=0.060) genes. At the gene-set level, association of abstinence length with variation in the glycine pathway was nominally significant (p=0.042 with STT=0.37). Marginal evidence of association with abstinence length was also observed for variation in the NMDA-receptor subunits (p<0.1 for STT<0.15).
Our findings suggest association of abstinence length in acamprosate-treated alcoholics with variation in the glycine signaling pathway and genes encoding NMDA receptor subunits. Investigation of the mechanisms underlying these associations and their usefulness for individualized treatment selection should follow.
The prevalence and impact of motor coordination difficulties in children with copy number variants associated with neurodevelopmental disorders (ND-CNVs) remains unknown. This study aims to advance understanding of motor coordination difficulties in children with ND-CNVs and establish relationships between intelligence quotient (IQ) and psychopathology.
169 children with an ND-CNV (67% male, median age = 8.88 years, range 6.02–14.81) and 72 closest-in-age unaffected siblings (controls; 55% male, median age = 10.41 years, s.d. = 3.04, range 5.89–14.75) were assessed with the Developmental Coordination Disorder Questionnaire, alongside psychiatric interviews and standardised assessments of IQ.
The children with ND-CNVs had poorer coordination ability (b = 28.98, p < 0.001) and 91% of children with an ND-CNV screened positive for suspected developmental coordination disorder, compared to 19% of controls (OR = 42.53, p < 0.001). There was no difference in coordination ability between ND-CNV genotypes (F = 1.47, p = 0.184). Poorer coordination in children with ND-CNV was associated with more attention deficit hyperactivity disorder (ADHD) (β = −0.18, p = 0.021) and autism spectrum disorder trait (β = −0.46, p < 0.001) symptoms, along with lower full-scale (ß = 0.21, p = 0.011), performance (β = −0.20, p = 0.015) and verbal IQ (β = 0.17, p = 0.036). Mediation analysis indicated that coordination ability was a full mediator of anxiety symptoms (69% mediated, p = 0.012), and a partial mediator of ADHD (51%, p = 0.001) and autism spectrum disorder trait symptoms (66%, p < 0.001) as well as full scale IQ (40%, p = 0.002), performance IQ (40%, p = 0.005) and verbal IQ (38%, p = 0.006) scores.
The findings indicate that poor motor coordination is highly prevalent and closely linked to risk of mental health disorder and lower intellectual function in children with ND-CNVs. Future research should explore whether early interventions for poor coordination ability could ameliorate neurodevelopmental risk.
The authors report on 7Li, 19F, and 1H pulsed field gradient NMR measurements of 26 organosilyl nitrile solvent-based electrolytes of either lithium bis(trifluorosulfonyl)imide (LiTFSI) or lithium hexafluorophosphate. Lithium transport numbers (as high as 0.50) were measured and are highest in the LiTFSI electrolytes. The authors also report on solvent blend electrolytes of fluoroorganosilyl (FOS) nitrile solvent mixed with ethylene carbonate (EC) and diethyl carbonate. Solvent diffusion measurements on an electrolyte with 6% FOS suggest both the FOS and EC solvate the lithium cation. By comparing lithium transport and transference numbers, the authors find less ion pairing in FOS nitrile carbonate blend electrolytes and difluoroorganosilyl nitrile electrolytes.
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
Disease surveillance in wildlife populations presents a logistical challenge, yet is critical in gaining a deeper understanding of the presence and impact of wildlife pathogens. Erinaceus coronavirus (EriCoV), a clade C Betacoronavirus, was first described in Western European hedgehogs (Erinaceus europaeus) in Germany. Here, our objective was to determine whether EriCoV is present, and if it is associated with disease, in Great Britain (GB). An EriCoV-specific BRYT-Green® real-time reverse transcription PCR assay was used to test 351 samples of faeces or distal large intestinal tract contents collected from casualty or dead hedgehogs from a wide area across GB. Viral RNA was detected in 10.8% (38) samples; however, the virus was not detected in any of the 61 samples tested from Scotland. The full genome sequence of the British EriCoV strain was determined using next generation sequencing; it shared 94% identity with a German EriCoV sequence. Multivariate statistical models using hedgehog case history data, faecal specimen descriptions and post-mortem examination findings found no significant associations indicative of disease associated with EriCoV in hedgehogs. These findings indicate that the Western European hedgehog is a reservoir host of EriCoV in the absence of apparent disease.
In recent years, ethnoarchaeology and the use of ethnographic analogy have come under increasing criticism. Analogy seems necessary because, as post-industrial academics, archaeologists worry that they do not possess the knowledge necessary to interpret archaeological materials directly and thus must consult with coeval ‘premodern’ peoples to develop interpretive baselines. In this paper, we draw attention to a form of scholarly enquiry – 19th-century Bible customs books – that faced a similar challenge and used methodologies that parallel archaeology's use of ethnoarchaeological data. These were books written by missionaries who lived in Palestine for extended periods of time and studied Palestinian life to make sense of obscure elements of the biblical text, believing that life there had remained fundamentally unchanged for the past three thousand years. Using the Bible customs books as a kind of ‘cautionary tale’ typical of ethnoarchaeology, we argue that a consideration of this literature brings into focus some of the challenges faced by archaeologists’ use of analogy. Specifically, Bible customs books expose significant issues in how relations are conceptualized between archaeologists, others and ancients, and show how a strict empirical focus in ethnographic research can insulate key assumptions from critical scrutiny.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
In Cameroon, there is a national programme engaged in the control of schistosomiasis and soil-transmitted helminthiasis. In certain locations, the programme is transitioning from morbidity control towards local interruption of parasite transmission. The volcanic crater lake villages of Barombi Mbo and Barombi Kotto are well-known transmission foci and are excellent context-specific locations to assess appropriate disease control interventions. Most recently they have served as exemplars of expanded access to deworming medications and increased environmental surveillance. In this paper, we review infection dynamics through time, beginning with data from 1953, and comment on the short- and long-term success of disease control. We show how intensification of local control is needed to push towards elimination and that further environmental surveillance, with targeted snail control, is needed to consolidate gains in preventive chemotherapy as well as empower local communities to take ownership of interventions.
With the push towards control and elimination of soil-transmitted helminthiasis and schistosomiasis in low- and middle-income countries, there is a need to develop alternative diagnostic assays that complement the current in-country resources, preferably at a lower cost. Here, we describe a novel high-resolution melt (HRM) curve assay with six PCR primer pairs, designed to sub-regions of the nuclear ribosomal locus. Used within a single reaction and dye detection channel, they are able to discriminate Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Ascaris lumbricoides, Trichuris trichiuria and Schistosoma spp. by HRM curve analysis. Here we describe the primers and the results of a pilot assessment whereby the HRM assay was tested against a selection of archived fecal samples from Ghanaian children as characterized by Kato–Katz and real-time PCR analysis with species-specific TaqMan hydrolysis probes. The resulting sensitivity and specificity of the HRM was 80 and 98.6% respectively. We judge the assay to be appropriate in modestly equipped and resourced laboratories. This method provides a potentially cheaper alternative to the TaqMan method for laboratories in lower resource settings. However, the assay requires a more extensive assessment as the samples used were not representative of all target organisms.
Previous reports investigating adiposity and cognitive function in the population allude to a negative association, although the relationship in older adults is unclear. The aim of this study was to investigate the association of adiposity (BMI and waist:hip ratio (WHR)) with cognitive function in community-dwelling older adults (≥60 years). Participants included 5186 adults from the Trinity Ulster Department of Agriculture ageing cohort study. Neuropsychological assessment measures included the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multi-variable linear regression models were used to assess the association between adiposity and cognitive function adjusting for insulin resistance, inflammation and cerebrovascular disease. The mean ages were 80·3 (sd 6·7), 71·0 (sd 7·3) and 70·2 (sd 6·3) years on the cognitive, bone and hypertensive cohorts, respectively. In the cognitive cohort, BMI was positively associated with immediate and delay memory, visuospatial/constructional ability, language and MMSE, and negatively with FAB (log-transformed), whereas WHR was negatively associated with attention. In the bone cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with visuospatial/constructional ability, attention and MMSE. In the hypertensive cohort, BMI was not associated with any cognitive domain, whereas WHR was negatively associated with immediate and delayed memory, visuospatial/constructional ability, language and MMSE and positively with FAB (log-transformed). In the cognitive and bone cohorts, the association of WHR and attention disappeared by further controlling for C-reactive protein and HbA1C. In this study of older adults, central adiposity was a stronger predictor of poor cognitive performance than BMI. Older adults could benefit from targeted public health strategies aimed at reducing obesity and obeseogenic risk factors to avoid/prevent/slow cognitive dysfunction.