Mitigating Contaminant-Driven Risks for the Safe Expansion of the Agricultural-Sanitation Circular Economy in an Urbanizing World.

The widespread adoption of an agricultural circular economy requires the recovery of resources such as water, organic matter, and nutrients from livestock manure and sanitation. While this approach offers many benefits, we argue this is not without potential risks to human and environmental health that largely stem from the presence of contaminants in the recycled resources (e.g., pharmaceuticals, pathogens). We discuss context specific challenges and solutions across the three themes: (1) contaminant monitoring; (2) collection transport and treatment; and (3) regulation and policy. We advocate for the redesign of sanitary and agricultural management practices to enable safe resource reuse in a proportionate and effective way. In populous urban regions with access to sanitation provision, processes can be optimized using emergent technologies to maximize removal of contaminant from excreta prior to reuse. Comparatively, in regions with limited existing capacity for conveyance of excreta to centralized treatment facilities, we suggest efforts should focus on creation of collection facilities (e.g., pit latrines) and decentralized treatment options such as composting systems. Overall, circular economy approaches to sanitation and resource management offer a potential solution to a pressing challenge; however, to ensure this is done in a safe manner, contaminant risks must be mitigated.

Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study.

BACKGROUND: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant. METHODS: In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths. FINDINGS: Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011). INTERPRETATION: Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort. FUNDING: University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council.

Author Correction: Scalable and robust SARS-CoV-2 testing in an academic center.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Determining the Origins of Human Immunodeficiency Virus Type 1 Drug-resistant Minority Variants in People Who Are Recently Infected Using Phylogenetic Reconstruction.

BACKGROUND: Drug-resistant minority variants (DRMinVs) detected in patients who recently acquired human immunodeficiency virus type 1 (HIV-1) can be transmitted, generated de novo through virus replication, or technical errors. The first form is likely to persist and result in treatment failure, while the latter two could be stochastic and transient. METHODS: Ultradeep sequencing of plasma samples from 835 individuals with recent HIV-1 infection in the United Kingdom was performed to detect DRMinVs at a mutation frequency between 2% and 20%. Sequence alignments including >110 000 HIV-1 partial pol consensus sequences from the UK HIV Drug Resistance Database (UK-HDRD), linked to epidemiological and clinical data from the HIV and AIDS Reporting System, were used for transmission cluster analysis. Transmission clusters were identified using Cluster Picker with a clade support of >90% and maximum genetic distances of 4.5% or 1.5%, the latter to limit detection to likely direct transmission events. RESULTS: Drug-resistant majority variants (DRMajVs) were detected in 66 (7.9%) and DRMinVs in 84 (10.1%) of the recently infected individuals. High levels of clustering to sequences in UK-HDRD were observed for both DRMajV (n = 48; 72.7%) and DRMinV (n = 63; 75.0%) sequences. Of these, 43 (65.2%) with DRMajVs were in a transmission cluster with sequences that harbored the same DR mutation compared to only 3 (3.6%) sequences with DRMinVs (P < .00001, Fisher exact test). Evidence of likely direct transmission of DRMajVs was observed for 25/66 (37.9%), whereas none were observed for the DRMinVs (P < .00001). CONCLUSIONS: Using a densely sampled HIV-infected population, we show no evidence of DRMinV transmission among recently infected individuals.

The Role of Google Scholar in Evidence Reviews and Its Applicability to Grey Literature Searching.

Google Scholar (GS), a commonly used web-based academic search engine, catalogues between 2 and 100 million records of both academic and grey literature (articles not formally published by commercial academic publishers). Google Scholar collates results from across the internet and is free to use. As a result it has received considerable attention as a method for searching for literature, particularly in searches for grey literature, as required by systematic reviews. The reliance on GS as a standalone resource has been greatly debated, however, and its efficacy in grey literature searching has not yet been investigated. Using systematic review case studies from environmental science, we investigated the utility of GS in systematic reviews and in searches for grey literature. Our findings show that GS results contain moderate amounts of grey literature, with the majority found on average at page 80. We also found that, when searched for specifically, the majority of literature identified using Web of Science was also found using GS. However, our findings showed moderate/poor overlap in results when similar search strings were used in Web of Science and GS (10-67%), and that GS missed some important literature in five of six case studies. Furthermore, a general GS search failed to find any grey literature from a case study that involved manual searching of organisations' websites. If used in systematic reviews for grey literature, we recommend that searches of article titles focus on the first 200 to 300 results. We conclude that whilst Google Scholar can find much grey literature and specific, known studies, it should not be used alone for systematic review searches. Rather, it forms a powerful addition to other traditional search methods. In addition, we advocate the use of tools to transparently document and catalogue GS search results to maintain high levels of transparency and the ability to be updated, critical to systematic reviews.

Frequency and patterns of protease gene resistance mutations in HIV-infected patients treated with lopinavir/ritonavir as their first protease inhibitor.

BACKGROUND: Selection of protease mutations on antiretroviral therapy (ART) including a ritonavir-boosted protease inhibitor (PI) has been reported infrequently. Scarce data exist from long-term cohorts on resistance incidence or mutational patterns emerging to different PIs. METHODS: We studied UK patients receiving lopinavir/ritonavir as their first PI, either while naive to ART or having previously received non-PI-based ART. Virological failure was defined as viral load ≥ 400 copies/mL after previous suppression <400 copies/mL, or failure to achieve <400 copies/mL during the first 6 months. pol sequences whilst failing lopinavir or within 30 days after stopping were analysed. Major and minor mutations (IAS-USA 2008-after exclusion of polymorphisms) were considered. Predicted susceptibility was determined using the Stanford HIVdb algorithm. RESULTS: Three thousand and fifty-six patients were followed for a median (IQR) of 14 (6-30) months, of whom 811 (27%) experienced virological failure. Of these, resistance test results were available on 291 (36%). One or more protease mutations were detected in 32 (11%) patients; the most frequent were I54V (n = 12), M46I (n = 11), V82A (n = 7) and L76V (n = 3). No association with viral subtype was evident. Many patients retained virus predicted to be susceptible to lopinavir (14, 44%), tipranavir (26, 81%) and darunavir (27, 84%). CONCLUSIONS: This study reflects the experience of patients in routine care. Selection of protease gene mutations by lopinavir/ritonavir occurred at a much higher rate than in clinical trials. The mutations observed showed only partial overlap with those previously identified by structural chemistry models, serial cell culture passage and genotype-phenotype analyses. There remained a low degree of predicted cross-resistance to other widely used PIs.

The impact of HIV drug resistance testing on changes to treatment.

BACKGROUND: We investigate changes made to therapy after a resistance test result and identify factors associated with switching regimen. METHODS: Patients receiving antiretroviral therapy (ART) who had a resistance test performed during 1998-2007 were included in the analysis. A switch was defined as starting at least two drugs/starting a drug from a class not previously experienced within 4 months of the resistance test result. Logistic regression was used to identify factors independently associated with switching regimen. RESULTS: Of the 5123 test results included in the analyses, 1874 (36.6%) were followed by a switch within 4 months of the test result. Independent factors associated with switching included genotypic sensitivity score (GSS) of the current regimen [odds ratio (OR) 4.86, 95% confidence interval (CI) 3.95, 5.97 for GSS less than 1 compared to GSS of at least 3] and a higher number of previous failures [1.12 (1.06, 1.18) per additional failed regimen]. Patients with fewer drug options were less likely to switch [0.36 (0.27, 0.48) comparing 0-3 drug options with ≥10 drug options]. CONCLUSIONS: Only 37% of patients switched regimen within 4 months of the resistance test result. Whilst toxicity concerns of available drugs may somewhat explain this finding, it is also likely that there is a lack of treatment options available for patients who did not switch.

The dynamics of appearance and disappearance of HIV-1 integrase mutations during and after withdrawal of raltegravir therapy.

OBJECTIVES: To monitor HIV-1 integrase resistance mutations during raltegravir (RAL) therapy, including the impact of RAL interruption. DESIGN AND METHOD: An analysis of viral load and the HIV-1 integrase gene evolution in 26 HIV-1 treatment-experienced patients undergoing RAL therapy. RESULTS: Initial suppression of viral load was observed in all patients; however, four patients failed to maintain suppression and subsequently developed resistance at viral load rebound. Mutations Q148R (2 months) followed by G140A/Q148R and then G140A/Y143CHR/Q148R/G163R were detected in the virus from one patient, and these reverted to wild type when treatment was withdrawn, although clonal analysis identified maintenance of RAL resistance minority species at this time point. RAL treatment was restarted after 6 months, and 2 weeks later, Y143CY/G163RG mutations appeared. In three other patients, viruses with N155H emerged at viral rebound either alone (2 months), followed by V151I (8 months) or alone (10 months), or together with V151I/G163RG (7 months). Loss of virus with the N155H mutation occurred in these patients when RAL therapy was terminated, despite maintenance of reverse transcriptase/polymerase resistance mutations. CONCLUSION: Complete viral suppression was important in order to prevent resistance emerging. RAL-resistance mutations were detected in the presence of other antiviral treatments, and the reverse of these mutations following RAL cessation suggests that a fitness deficit was conferred by these mutants. The observation that following RAL interruption virus rebound was with previously existing reverse transcriptase/polymerase mutations in the absence of integrase mutations implies that it is pre-RAL-archived viruses that re-emerge.

Judging mental disorder in youths: Effects of client, clinician, and contextual differences.

Using a vignette-based, mailed survey of 1,401 experienced psychologists, psychiatrists, and social workers, the authors examined how clients' race/ethnicity and clinicians' professional and social characteristics affect their judgment of mental disorder among antisocially behaving youths. Vignettes described problematic behaviors meeting the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) criteria for conduct disorder but contained contextual information suggesting either disorder or nondisorder, following DSM-IV guidelines. Clinicians depended on contextual information to decide whether a mental disorder existed, and they judged White youths to have a disorder more frequently than Black or Hispanic youths. Clinicians' occupation, theoretical orientation, and age also were associated with disorder judgments, whereas their gender, race, and experience were not. Research and training implications of these variations in clinical judgments are discussed.

Social workers' attitudes about psychotropic drug treatment with youths.

There is considerable controversy among mental health professionals and the public about the proper role of psychotropic medications in the treatment of youths. Within social work, too, there have been sharp differences of opinion. There have been few studies, however, about the views of practicing clinical social workers on the use of psychiatric drugs in the treatment of youths. This study, a cross-sectional survey of a national sample of social workers, examines their views about medications and the role they may play in the treatment of youths.The findings suggest that social workers hold complex views that recognize both the potential benefits and harms ofpsychotropic medications, but overall they seem to support their use in a judicious manner.

The lay concept of conduct disorder: do nonprofessionals use syndromal symptoms or internal dysfunction to distinguish disorder from delinquency?

BACKGROUND: Conduct disorder (CD) must be distinguished from nondisordered delinquent behaviour to avoid false positives, especially when diagnosing youth from difficult environments. However, the nature of this distinction remains controversial. The DSM-IV observes that its own syndromal CD diagnostic criteria conflict with its definition of mental disorder, which requires that symptoms be considered a manifestation of internal dysfunction to warrant disorder diagnosis. Previous research indicates that professional judgments tend to be guided by the dysfunction requirement, not syndromal symptoms alone. However, there are almost no data on lay conceptualizations. Thus it remains unknown whether judgments about CD are anchored in a broadly shared understanding of mental disorder that provides a basis for professional-lay consensus. OBJECTIVE: The present study tests which conception of CD, syndromal-symptoms or dysfunction-requirement, corresponds most closely to lay judgments of disorder or nondisorder and compares lay and professional judgments. We hypothesized that lay disorder judgments, like professional judgments, tend to presuppose the dysfunction requirement. METHOD: Three lay samples (nonclinical social workers, nonpsychiatric nurses, and undergraduates) rated their agreement that youths described in clinical vignettes have a mental disorder. All vignettes satisfied DSM-IV CD diagnostic criteria. Vignettes were varied to present syndromal symptoms only, symptoms suggesting internal dysfunction, and symptoms resulting from reactions to negative circumstances, without dysfunction. RESULTS: All lay samples attributed disorder more often to youths whose symptoms suggested internal dysfunction than to youths with similar symptoms but without a likely dysfunction. CONCLUSIONS: The dysfunction requirement appears to reflect a widely shared lay and professional concept of disorder.

Politics of personnel and landscapes of knowledge.

This is a commentary on three articles on bibliometrics in social work that appear in this issue of the journal. I argue that bibliometrics can make many contributions to the study of the structure and evolution of social work's knowledge base, but it cannot completely remove subjectivity in the evaluation of the scholarship of individual faculty, where legitimate differences of professional opinion will remain.

Diagnostic consistency in assessing conduct disorder: an experiment on the effect of social context.

The major objective of the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders (see, e.g., the 4th ed., American Psychiatric Association, 1994) has been to achieve better diagnostic consistency. This has proved to be an elusive goal, because the diagnostic criteria and their rules for application can be ambiguous. This study mailed systematically varied case vignettes of conduct disorder to a nationally representative sample of 1,500 mental health clinicians in order to examine the effect of social context on diagnostic consistency. It found that consistency of diagnosis was modest and that it was affected by context and varied by profession.

The effect of social context on psychiatrists' judgments of adolescent antisocial behavior.

BACKGROUND: The DSM assumes that mental disorders can be identified by the presence of specific co-occurring symptoms associated with certain duration and impaired functioning, independent of the social context in which symptoms occur. The validity of this assumption was tested using the judgments of experienced psychiatrists. We hypothesized that psychiatrists would judge an identical set of adolescent antisocial behaviors, meeting the DSM-IV diagnostic criteria for conduct disorder, as indicative of mental disorder or non-disordered problem-in-living, depending on the social context. METHOD: A representative sample of 483 psychiatrists in the United States read one of three experimentally manipulated vignettes depicting adolescent antisocial behavior and responded to questions concerning its nature, prognosis, cause, and response to various treatments. RESULTS: Results supported our hypothesis. Under some circumstances, a youth may exhibit behaviors that meet the DSM-IV diagnostic criteria for conduct disorder, but be judged by psychiatrists as not having a mental disorder. In addition, as predicted, psychiatrists reached different judgments about course, etiology, and treatment responsiveness when the identical behaviors occurred in different social contexts. CONCLUSIONS: The findings illuminate weaknesses in the validity of classification systems based on behavioral criteria independent of their social context. Implications of findings are discussed.

Should the DSM-IV diagnostic criteria for conduct disorder consider social context?

OBJECTIVE: The text of the DSM-IV states that a diagnosis of conduct disorder should be made only if symptoms are caused by an internal psychological dysfunction and not if symptoms are a reaction to a negative environment. However, the DSM-IV diagnostic criteria are purely behavioral and ignore this exclusion. This study empirically evaluated which approach--the text's negative-environment exclusion or the purely behavioral criteria--is more consistent with clinicians' intuitive judgments about whether a disorder is present, whether professional help is needed, and whether the problem is likely to continue. METHOD: Clinically experienced psychology and social work graduate students were presented with three variations of vignettes describing youths whose behavior satisfied the DSM-IV criteria for conduct disorder. The three variations presented symptoms only, symptoms caused by internal dysfunction, and symptoms caused by reactions to a negative environment. The clinicians rated their level of agreement that the youth described in the vignette had a disorder, needed professional mental health help, and had a problem that was likely to continue into adulthood. RESULTS: Youths with symptoms caused by internal dysfunction were judged to have a disorder, and those with a reaction to a negative environment not to have a disorder. The difference was not explained by the clinicians' judgments of the youths' need for professional help or the expected duration of symptoms. CONCLUSIONS: The clinicians' judgments supported the validity of the DSM-IV's textual claim that a diagnosis of conduct disorder is valid only when symptoms are due to an internal dysfunction.

Effectiveness of community services for discharged mental hospital patients.

This study of 579 state hospital patients charts the pattern of their care in the community in the two or three years following hospital discharge, and examines the relationship of aftercare services to readmission rates. Findings suggest that, among the most chronic patients, a substantial number of aftercare visits may be related to lower hospital readmission rates.