Planarians recruit piRNAs for mRNA turnover in adult stem cells.

PIWI proteins utilize small RNAs called piRNAs to silence transposable elements, thereby protecting germline integrity. In planarian flatworms, PIWI proteins are essential for regeneration, which requires adult stem cells termed neoblasts. Here, we characterize planarian piRNAs and examine the roles of PIWI proteins in neoblast biology. We find that the planarian PIWI proteins SMEDWI-2 and SMEDWI-3 cooperate to degrade active transposons via the ping-pong cycle. Unexpectedly, we discover that SMEDWI-3 plays an additional role in planarian mRNA surveillance. While SMEDWI-3 degrades numerous neoblast mRNAs in a homotypic ping-pong cycle, it is also guided to another subset of neoblast mRNAs by antisense piRNAs and binds these without degrading them. Mechanistically, the distinct activities of SMEDWI-3 are primarily dictated by the degree of complementarity between target mRNAs and antisense piRNAs. Thus, PIWI proteins enable planarians to repurpose piRNAs for potentially critical roles in neoblast mRNA turnover.

Strategies for obstetricians and gynecologists to advance reproductive autonomy in a post-Roe landscape.

The monumental reversal of Roe vs Wade dramatically impacted the landscape of reproductive healthcare access in the United States. The decision most significantly affects communities that historically have been and continue to be marginalized by systemic racism, classism, and ableism within the medical system. To minimize the harm of restrictive policies that have proliferated since the Supreme Court overturned Roe, it is incumbent on obstetrician-gynecologists to modify practice patterns to meet the pressing reproductive health needs of their patients and communities. Change will require cross-discipline advocacy focused on advancing equity and supporting the framework of reproductive justice. Now, more than ever, obstetrician-gynecologists have a critical responsibility to implement new approaches to service delivery and education that will expand access to evidence-based, respectful, and person-centered family planning and early pregnancy care regardless of their practice location or subspecialty.

Emin: A First-Principles Thermochemical Descriptor for Predicting Molecular Synthesizability.

Predicting the synthesizability of a new molecule remains an unsolved challenge that chemists have long tackled with heuristic approaches. Here, we report a new method for predicting synthesizability using a simple yet accurate thermochemical descriptor. We introduce Emin, the energy difference between a molecule and its lowest energy constitutional isomer, as a synthesizability predictor that is accurate, physically meaningful, and first-principles based. We apply Emin to 134,000 molecules in the QM9 data set and find that Emin is accurate when used alone and reduces incorrect predictions of "synthesizable" by up to 52% when used to augment commonly used prediction methods. Our work illustrates how first-principles thermochemistry and heuristic approximations for molecular stability are complementary, opening a new direction for synthesizability prediction methods.

Radical Stereochemistry: Accounting for Diastereomers in Kinetic Mechanism Development.

Recent work in combustion and atmospheric chemistry has revealed cases in which diastereomers must be distinguished to accurately model a reacting flow. This paper presents an open-source framework for introducing such stereoisomer resolution into a kinetic mechanism. We detail our definitions and algorithms for labeling and enumerating the stereoisomers of a molecule and then generalize our system to describe the transition state (TS) of a reaction. This allows for the stereospecific enumeration of reactants and products while accounting for "fleeting" stereochemistry that is unique to the TS. We also present the AutoMech Chemical Identifier (AMChI), an InChI-like string identifier that accounts for stereocenters omitted by InChI. This identifier is extended to describe the TSs of reactions, providing a universal lookup key for specific reaction channels. The final piece of our methodology is an analytic formula to remove redundancy from a stereoresolved mechanism when its enantiomers exist as a racemic mixture, making it as compact as possible while fully accounting for the differences between diastereomers. In applying our methodology to two subsets of the NUIGMech1.1 mechanism, we find that our approach reduces the extra species added for large-fuel oxidation from 2231 (133%, full expansion) to 694 (41%, nonredundant expansion). We also find that for pyrolysis more than a quarter of the species in the expanded mechanism cannot be properly described by an InChI string, requiring an AMChI string to communicate their identity. Finally, we find that roughly one-quarter of the large-fuel oxidation reactions and one-third of the pyrolysis reactions include fleeting TS stereochemistry, which may have relevant effects on their kinetics.

Indigenous maternal and infant outcomes and women's experiences of midwifery care: A mixed-methods systematic review.

BACKGROUND: The impact of midwifery, and especially Indigenous midwifery, care for Indigenous women and communities has not been comprehensively reviewed. To address this knowledge gap, we conducted a mixed-methods systematic review to understand Indigenous maternal and infant outcomes and women's' experiences with midwifery care. METHODS: We searched nine databases to identify primary studies reporting on midwifery and Indigenous maternal and infant birth outcomes and experiences, published in English since 2000. We synthesized quantitative and qualitative outcome data using a convergent segregated mixed-methods approach and used a mixed-methods appraisal tool (MMAT) to assess the methodological quality of included studies. The Aboriginal and Torres Strait Islander Quality Appraisal Tool (ATSI QAT) was used to appraise the inclusion of Indigenous perspectives in the evidence. RESULTS: Out of 3044 records, we included 35 individual studies with 55% (19 studies) reporting on maternal and infant health outcomes. Comparative studies (n = 13) showed no significant differences in mortality rates but identified reduced preterm births, earlier prenatal care, and an increased number of prenatal visits for Indigenous women receiving midwifery care. Quality of care studies indicated a preference for midwifery care among Indigenous women. Sixteen qualitative studies highlighted three key findings - culturally safe care, holistic care, and improved access to care. The majority of studies were of high methodological quality (91% met ≥80% criteria), while only 14% of studies were considered to have appropriately included Indigenous perspectives. CONCLUSION: This review demonstrates the value of midwifery care for Indigenous women, providing evidence to support policy recommendations promoting midwifery care as a physically and culturally safe model for Indigenous women and families.

'It's quite a balancing act': A qualitative study of parents' experiences and information needs related to the COVID-19 pandemic.

INTRODUCTION: Throughout the coronavirus disease 2019 (COVID-19) pandemic, parents and children faced significant challenges as a result of prevention measures implemented to control the spread of the disease. Ensuring that families have access to essential health information is critical for improving health outcomes and adherence to public health recommendations. Understanding parents' experiences and information needs related to the pandemic and associated health measures (e.g., vaccination, mask wearing, social distancing, etc.) will inform the development and dissemination of resources tailored to parents' needs to support informed decision making. METHODS: We conducted a qualitative descriptive study. Between September and November 2021, parents across Canada were recruited online via social media and community organisation newsletters and listservs to participate in focus groups via Zoom. Focus groups were audio-recorded and transcribed verbatim. Data were coded and analysed using thematic analysis. Participants completed a demographic questionnaire before the focus groups (via SimpleSurveys). RESULTS: Sixty-seven parents participated in 12 focus groups between October and November 2021. In relation to experiences, parents felt they were (1) constantly trying to balance everything, and (2) trying to do their best with the information they had at the time when making decisions. Regarding information needs, parents reflected on (1) how difficult it was navigating copious amounts of changing information and finding credible sources to rely on, (2) the need for resources that were easily accessible, credible and in plain language and (3) the need for resources that were tailored to their needs to support them and their children make informed decisions. CONCLUSIONS: Trying to mitigate the risk of COVID-19 infection and adhere to public health recommendations, while balancing various factors (work, online learning, and social interactions) and navigating changing information, was overwhelming for many parents. Reflecting on their needs, parents suggested tailored resources that provided concise, credible information in plain language to help them make informed decisions and navigate conflicting information. These findings reveal important knowledge gaps and highlight areas that need to be addressed to support parents during the pandemic period and beyond. PATIENT OR PUBLIC CONTRIBUTION: Members of our established Paediatric Parent Advisory Group (P-PAG) were involved as collaborators throughout the planning (grant proposal), development and execution of the study. P-PAG members gave input on the design of the questionnaire, interview guide, recruitment strategy and interpretation of findings.

Understanding How Youth Search for Mental Health Information Online: A Qualitative Descriptive Study.

The objective of this study was to understand how youth search for mental health information online. Youth partners were engaged at the onset of the project and provided input throughout on the design, conduct and analysis. Individual, semi-structured interviews with Canadian youth with experience searching for mental health information online were conducted. Data collection and reflexive thematic analysis proceeded concurrently. Fourteen youth were interviewed. Four main themes related to how youth search online emerged: mind-set shapes the search process; external factors shape the search process; key attributes of helpful information; and cues affecting trustworthiness of online information. Findings can inform the development of youth-friendly online mental health information that is perceived as helpful and trustworthy by youth. Ensuring youth have access to quality online mental health information, accessible to how they search for it, is critical to the mental health and development of youth.

OH Roaming and Beyond in the Unimolecular Decay of the Methyl-Ethyl-Substituted Criegee Intermediate: Observations and Predictions.

Alkene ozonolysis generates short-lived Criegee intermediates that are a significant source of hydroxyl (OH) radicals. This study demonstrates that roaming of the separating OH radicals can yield alternate hydroxycarbonyl products, thereby reducing the OH yield. Specifically, hydroxybutanone has been detected as a stable product arising from roaming in the unimolecular decay of the methyl-ethyl-substituted Criegee intermediate (MECI) under thermal flow cell conditions. The dynamical features of this novel multistage dissociation plus a roaming unimolecular decay process have also been examined with ab initio kinetics calculations. Experimentally, hydroxybutanone isomers are distinguished from the isomeric MECI by their higher ionization threshold and distinctive photoionization spectra. Moreover, the exponential rise of the hydroxybutanone kinetic time profile matches that for the unimolecular decay of MECI. A weaker methyl vinyl ketone (MVK) photoionization signal is also attributed to OH roaming. Complementary multireference electronic structure calculations have been utilized to map the unimolecular decay pathways for MECI, starting with 1,4 H atom transfer from a methyl or methylene group to the terminal oxygen, followed by roaming of the separating OH and butanonyl radicals in the long-range region of the potential. Roaming via reorientation and the addition of OH to the vinyl group of butanonyl is shown to yield hydroxybutanone, and subsequent C-O elongation and H-transfer can lead to MVK. A comprehensive theoretical kinetic analysis has been conducted to evaluate rate constants and branching yields (ca. 10-11%) for thermal unimolecular decay of MECI to conventional and roaming products under laboratory and atmospheric conditions, consistent with the estimated experimental yield (ca. 7%).

OH Roaming during the Ozonolysis of α-Pinene: A New Route to Highly Oxygenated Molecules?

The formation of low-volatility organic compounds in the ozonolysis of α-pinene, the dominant atmospheric monoterpene, provides an important route to aerosol formation. In this work, we consider a previously unexplored set of pathways for the formation of highly oxygenated molecules in α-pinene ozonolysis. Pioneering, direct experimental observations of Lester and co-workers have demonstrated a significant production of hydroxycarbonyl products in the dissociation of Criegee intermediates. Theoretical analyses indicate that this production arises from OH roaming-induced pathways during the OO fission of the vinylhydroperoxides (VHPs), which in turn come from internal H transfers in the Criegee intermediates. Ab initio kinetics computations are used here to explore the OH roaming-induced channels that arise from the ozonolysis of α-pinene. For computational reasons, the calculations consider a surrogate for α-pinene, where two spectator methyl groups are replaced with H atoms. Multireference electronic structure calculations are used to illustrate a variety of energetically accessible OH roaming pathways for the four VHPs arising from the ozonolysis of this α-pinene surrogate. Ab initio transition-state theory-based master equation calculations indicate that for the dissociation of stabilized VHPs, these OH roaming pathways are kinetically significant with a branching that generally increases from ∼20% at room temperature up to ∼70% at lower temperatures representative of the troposphere. For one of the VHPs, this branching already exceeds 60% at room temperature. For the overall ozonolysis process, these branching ratios would be greatly reduced by a limited branching to the stabilized VHP, although there would also be some modest roaming fraction for the nonthermal VHP dissociation process. The strong exothermicities of the roaming-induced isomerizations/additions and abstractions suggest new routes to fission of the cyclobutane rings. Such ring fissions would facilitate further autoxidation reactions, thereby providing a new route for producing highly oxygenated nonvolatile precursors to aerosol formation.

High-Accuracy Heats of Formation for Alkane Oxidation: From Small to Large via the Automated CBH-ANL Method.

It is generally challenging to obtain high-accuracy predictions for the heat of formation for species with more than a handful of heavy atoms, such as those of importance in standard combustion mechanisms. To this end, we construct the CBH-ANL approach and illustrate that, for a set of 194 alkane oxidation species, it can be used to produce ΔHf(0 K) values with 2σ uncertainties of 0.2-0.5 kcal mol-1. This set includes the alkanes, hydroperoxides, and alkyl, peroxy, and hydroperoxyalkyl radicals for 17 representative hydrocarbon fuels containing up to 10 heavy atoms with various degrees of branching in the alkane backbone. The CBH-ANL approach, automated in the QTC and AutoMech software suites, builds balanced chemical equations for the calculation of ΔHf(0 K), in which the reference species may be up to five heavy atoms. The high-level ANL0 and ANL1 reference ΔHf(0 K) values are further refined for even the largest of these reference species with a novel laddering approach. We perform a comprehensive quantification of the uncertainties for both the individual reference species (the largest of which is 0.15 kcal mol-1) and the propagation of those uncertainties when used in the calculation of ΔHf(0 K) for the 194 target species. We examine the sensitivity of the predicted ΔHf(0 K) values to (i) electronic energies from various methods, including ωB97X-D/cc-pVTZ, B2PLYP-D3/cc-pVTZ, CCSD(T)-F12b/cc-pVDZ-F12//B2PLYP-D3/cc-pVTZ, and CCSD(T)-F12b/cc-pVTZ-F12//B2PLYP-D3/cc-pVTZ; (ii) the zero-point vibrational energies (ZPVEs), where we consider harmonic ZPVEs as well as two scaling-based estimates of the anharmonic ZPVEs, all implemented for both ωB97X-D/cc-pVTZ and B2PLYP-D3/cc-pVTZ calculations; (iii) the particular CBH-ANL scheme employed; and (iv) the procedure for choosing the reference conformer for the analyses. The discussion concludes with a summary of the estimated overall uncertainty in the predictions and a validation of the predictions for the alkane subset.

Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms.

mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid-encoded version of 2-12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.

A high-protein total diet replacement alters the regulation of food intake and energy homeostasis in healthy, normal-weight adults.

PURPOSE: Dietary intake can affect energy homeostasis and influence body weight control. The aim of this study was to compare the impact of high-protein total diet replacement (HP-TDR) versus a control (CON) diet in the regulation of food intake and energy homeostasis in healthy, normal-weight adults. METHODS: In this acute randomized controlled, cross-over study, participants completed two isocaloric arms: a) HP-TDR: 35% carbohydrate, 40% protein, and 25% fat; b) CON: 55% carbohydrate, 15% protein, and 30% fat. The diets were provided for 32 h while inside a whole-body calorimetry unit. Appetite sensations, appetite-related hormones, and energy metabolism were assessed. RESULTS: Forty-three healthy, normal-weight adults (19 females) participated. Appetite sensations did not differ between diets (all p > 0.05). Compared to the CON diet, the change in fasting blood markers during the HP-TDR intervention was smaller for peptide tyrosine-tyrosine (PYY; - 18.9 ± 7.9 pg/mL, p = 0.02) and greater for leptin (1859 ± 652 pg/mL, p = 0.007). Moreover, postprandial levels of glucagon-like peptide 1 (1.62 ± 0.36 pM, p < 0.001) and PYY (31.37 ± 8.05 pg/mL, p < 0.001) were higher in the HP-TDR. Significant correlations were observed between energy balance and satiety (r = - 0.41, p = 0.007), and energy balance and PFC (r = 0.33, p = 0.033) in the HP-TDR. CONCLUSION: Compared to the CON diet, the HP-TDR increased blood levels of anorexigenic hormones. Moreover, females and males responded differently to the intervention in terms of appetite sensations and appetite-related hormones. TRIAL REGISTRATION: NCT02811276 (retrospectively registered on 16 June 2016) and NCT03565510 (retrospectively registered on 11 June 2018).

Dysregulation in Multiple Transcriptomic Endometrial Pathways Is Associated with Recurrent Implantation Failure and Recurrent Early Pregnancy Loss.

Overlapping disease aetiologies associated with multiple altered biological processes have been identified that change the endometrial function leading to recurrent implantation failure (RIF) and recurrent early pregnancy loss (REPL). We aimed to provide a detailed insight into the nature of the biological malfunction and related pathways of differentially expressed genes in RIF and REPL. Endometrial biopsies were obtained from 9 women experiencing RIF, REPL and control groups. Affymetrix microarray analysis was performed to measure the gene expression level of the endometrial biopsies. Unsupervised clustering of endometrial samples shows scattered distribution of gene expression between the RIF, REPL and control groups. 2556 and 1174 genes (p value < 0.05, Fold change > 1.2) were significantly altered in the endometria of RIF and REPL patients' group, respectively compared to the control group. Downregulation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the differentially expressed genes (DEGs) in RIF and REPL including ribosome and oxidative phosphorylation pathways. Gene Ontology (GO) analysis revealed ribosomes and mitochondria inner membrane as the most significantly downregulated cellular component (CC) affected in RIF and REPL. Determination of the dysregulated genes and related biological pathways in RIF and REPL will be key in understanding their molecular pathology and of major importance in addressing diagnosis, prognosis, and treatment issues

Substitution Reactions in the Pyrolysis of Acetone Revealed through a Modeling, Experiment, Theory Paradigm.

The development of high-fidelity mechanisms for chemically reactive systems is a challenging process that requires the compilation of rate descriptions for a large and somewhat ill-defined set of reactions. The present unified combination of modeling, experiment, and theory provides a paradigm for improving such mechanism development efforts. Here we combine broadband rotational spectroscopy with detailed chemical modeling based on rate constants obtained from automated ab initio transition state theory-based master equation calculations and high-level thermochemical parametrizations. Broadband rotational spectroscopy offers quantitative and isomer-specific detection by which branching ratios of polar reaction products may be obtained. Using this technique, we observe and characterize products arising from H atom substitution reactions in the flash pyrolysis of acetone (CH3C(O)CH3) at a nominal temperature of 1800 K. The major product observed is ketene (CH2CO). Minor products identified include acetaldehyde (CH3CHO), propyne (CH3CCH), propene (CH2CHCH3), and water (HDO). Literature mechanisms for the pyrolysis of acetone do not adequately describe the minor products. The inclusion of a variety of substitution reactions, with rate constants and thermochemistry obtained from automated ab initio kinetics predictions and Active Thermochemical Tables analyses, demonstrates an important role for such processes. The pathway to acetaldehyde is shown to be a direct result of substitution of acetone's methyl group by a free H atom, while propene formation arises from OH substitution in the enol form of acetone by a free H atom.

Creating efficiencies in the extraction of data from randomized trials: a prospective evaluation of a machine learning and text mining tool.

BACKGROUND: Machine learning tools that semi-automate data extraction may create efficiencies in systematic review production. We evaluated a machine learning and text mining tool's ability to (a) automatically extract data elements from randomized trials, and (b) save time compared with manual extraction and verification. METHODS: For 75 randomized trials, we manually extracted and verified data for 21 data elements. We uploaded the randomized trials to an online machine learning and text mining tool, and quantified performance by evaluating its ability to identify the reporting of data elements (reported or not reported), and the relevance of the extracted sentences, fragments, and overall solutions. For each randomized trial, we measured the time to complete manual extraction and verification, and to review and amend the data extracted by the tool. We calculated the median (interquartile range [IQR]) time for manual and semi-automated data extraction, and overall time savings. RESULTS: The tool identified the reporting (reported or not reported) of data elements with median (IQR) 91% (75% to 99%) accuracy. Among the top five sentences for each data element at least one sentence was relevant in a median (IQR) 88% (83% to 99%) of cases. Among a median (IQR) 90% (86% to 97%) of relevant sentences, pertinent fragments had been highlighted by the tool; exact matches were unreliable (median (IQR) 52% [33% to 73%]). A median 48% of solutions were fully correct, but performance varied greatly across data elements (IQR 21% to 71%). Using ExaCT to assist the first reviewer resulted in a modest time savings compared with manual extraction by a single reviewer (17.9 vs. 21.6 h total extraction time across 75 randomized trials). CONCLUSIONS: Using ExaCT to assist with data extraction resulted in modest gains in efficiency compared with manual extraction. The tool was reliable for identifying the reporting of most data elements. The tool's ability to identify at least one relevant sentence and highlight pertinent fragments was generally good, but changes to sentence selection and/or highlighting were often required. PROTOCOL: https://doi.org/10.7939/DVN/RQPJKS.

Machine-Learning Predictions of High Arsenic and High Manganese at Drinking Water Depths of the Glacial Aquifer System, Northern Continental United States.

Globally, over 200 million people are chronically exposed to arsenic (As) and/or manganese (Mn) from drinking water. We used machine-learning (ML) boosted regression tree (BRT) models to predict high As (>10 µg/L) and Mn (>300 µg/L) in groundwater from the glacial aquifer system (GLAC), which spans 25 states in the northern United States and provides drinking water to 30 million people. Our BRT models' predictor variables (PVs) included recently developed three-dimensional estimates of a suite of groundwater age metrics, redox condition, and pH. We also demonstrated a successful approach to significantly improve ML prediction sensitivity for imbalanced data sets (small percentage of high values). We present predictions of the probability of high As and high Mn concentrations in groundwater, and uncertainty, at two nonuniform depth surfaces that represent moving median depths of GLAC domestic and public supply wells within the three-dimensional model domain. Predicted high likelihood of anoxic condition (high iron or low dissolved oxygen), predicted pH, relative well depth, several modeled groundwater age metrics, and hydrologic position were all PVs retained in both models; however, PV importance and influence differed between the models. High-As and high-Mn groundwater was predicted with high likelihood over large portions of the central part of the GLAC.

Behavioural and cognitive behavioural therapy for obsessive compulsive disorder (OCD) in individuals with autism spectrum disorder (ASD).

BACKGROUND: Autistic spectrum disorder (ASD) is an increasingly recognised neurodevelopmental condition; that is, a neurologically-based condition which interferes with the acquisition, retention or application of specific skills. ASD is characterised by challenges with socialisation and communication, and by stereotyped and repetitive behaviours. A stereotyped behaviour is one which is repeated over and over again and which seems not to have any useful function. ASD often co-occurs with mental health disorders, including obsessive compulsive disorder (OCD). People with ASD may show certain cognitive differences (i.e. differences in ways of thinking) which influence their response to therapies. Thus, there is a need for evidence-based guidelines to treat mental health issues in this group. OCD, a common condition characterised by repeated obsessional thoughts and compulsive acts, occurs with greater frequency in persons with ASD than in the general population. Genetic, anatomic, neurobiological and psychological factors have been proposed to explain this co-occurrence. However, care should be taken to distinguish stereotyped and repetitive behaviours characteristic of ASD from obsessive compulsive acts in OCD. Cognitive behavioural therapy (CBT) is the recommended treatment for OCD, but studies have suggested that this treatment may be less effective in those with OCD co-occurring with ASD. Hence, modifications to CBT treatment may be helpful when treating OCD co-occurring with ASD to optimise outcomes. OBJECTIVES: To assess the effectiveness of behavioural and cognitive behavioural therapy for obsessive compulsive disorder (OCD) in children and adults with autism spectrum disorder (ASD). SEARCH METHODS: We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, five other bibliographic databases, international trial registries and other sources of grey literature (to 24 August 2020). We checked the reference lists of included studies and relevant systematic reviews to identify additional studies missed from the original electronic searches. We contacted subject experts for further information when needed. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cross-over, cluster- and quasi-randomised controlled trials involving both adults and children with diagnoses of OCD and ASD. We included studies of participants with co-occurring conditions (i.e. those experiencing other mental illnesses or neurodevelopmental conditions at the same time), but we did not include individuals who had a co-occurring global learning difficulty. Treatment could be in any setting or format and include behavioural therapy (BT) and cognitive behavioural therapy (CBT), which may have been adapted for those with ASD. Comparator interventions included no treatment, waiting list, attention placebo (where the control group receives non-specific aspects of therapy, but not the active ingredient) and treatment as usual (TAU, where the control group receives the usual treatment, according to accepted standards). DATA COLLECTION AND ANALYSIS: Three review authors independently screened studies for inclusion. The authors extracted relevant data from the one eligible study, assessed the risk of bias and certainty of evidence (GRADE). Outcomes of interest were changes in OCD symptoms and treatment completion (primary outcome), and severity of depressive symptoms, anxiety symptoms and behavioural difficulties, as well as degree of family accommodation (secondary outcomes). We did not conduct meta-analyses as only one study met the selection criteria. MAIN RESULTS: We included only one RCT of 46 participants in our analysis. This study compared CBT for OCD in persons with high-functioning ASD with a control group who received anxiety management only. There were no differences in rates of treatment completion between the CBT (87%) and anxiety management (87%) groups (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.80 to 1.25; low-certainty evidence). Behavioural difficulties were not included as an outcome measure in the study. This study showed that there may be a benefit at the end of treatment favouring CBT compared with anxiety management in OCD symptoms (mean difference (MD) -3.00, 95% CI -8.02 to 2.02), depression symptoms (MD -1.80, 95% CI -11.50 to 7.90), anxiety symptoms (MD -3.20, 95% CI -11.38 to 4.98), and quality of life (MD 5.20, 95% CI -1.41 to 11.81), but the evidence was of low certainty.  AUTHORS' CONCLUSIONS: Evidence is limited regarding the efficacy of CBT for treatment of OCD in ASD. There is much scope for future study, not only examining the efficacy of CBT for OCD in ASD, but also the particular ways that OCD manifests in and affects people with ASD and the role of the family in treatment response.

Research- and health-related youth advisory groups in Canada: An environmental scan with stakeholder interviews.

BACKGROUND: Engaging youth throughout the research process improves research quality and outcomes. Youth advisory groups provide one way for youth to express their opinions on relevant issues. OBJECTIVE: This study aimed to identify research- and health-related youth advisory groups ('groups') in Canada and understand the best practices of these groups. METHODS: Google searches and supplementary methods were used to identify relevant groups in Canada. Group information was extracted from websites or through interviews with key informants. RESULTS: We identified 40 groups. Groups were commonly part of a hospital/healthcare facility, nonprofit/health organization or research group. The majority focused on a specific content area, most commonly, mental health. Over half the groups advised on health services. Members' ages ranged from 9 to 35 years. The number of members ranged from 5 to 130. Interviews (n = 12) identified seven categories relating to group practices: (a) group purpose/objectives, (b) group development, (c) group operations, (d) group structure, (e) adult involvement, (f) membership and recruitment and (g) group access. Challenges and facilitators to the success of groups were described within the following themes: (a) retaining engagement, (b) creating a safe environment and (c) putting youth in positions of influence. Advice and recommendations were provided regarding the development of a new group. CONCLUSION: This study provides a comprehensive overview of research- and health-related youth advisory groups in Canada. This information can be used to identify groups that stakeholders could access as well as inform the development of a new group. PATIENT OR PUBLIC CONTRIBUTION: Youth advisory group representatives were interviewed as part of the study.

Agricultural origins on the Anatolian plateau.

This paper explores the explanations for, and consequences of, the early appearance of food production outside the Fertile Crescent of Southwest Asia, where it originated in the 10th/9th millennia cal BC. We present evidence that cultivation appeared in Central Anatolia through adoption by indigenous foragers in the mid ninth millennium cal BC, but also demonstrate that uptake was not uniform, and that some communities chose to actively disregard cultivation. Adoption of cultivation was accompanied by experimentation with sheep/goat herding in a system of low-level food production that was integrated into foraging practices rather than used to replace them. Furthermore, rather than being a short-lived transitional state, low-level food production formed part of a subsistence strategy that lasted for several centuries, although its adoption had significant long-term social consequences for the adopting community at Boncuklu. Material continuities suggest that Boncuklu's community was ancestral to that seen at the much larger settlement of Çatalhöyük East from 7100 cal BC, by which time a modest involvement with food production had been transformed into a major commitment to mixed farming, allowing the sustenance of a very large sedentary community. This evidence from Central Anatolia illustrates that polarized positions explaining the early spread of farming, opposing indigenous adoption to farmer colonization, are unsuited to understanding local sequences of subsistence and related social change. We go beyond identifying the mechanisms for the spread of farming by investigating the shorter- and longer-term implications of rejecting or adopting farming practices.

Effectiveness and safety of interventions to manage childhood overweight and obesity: An Overview of Cochrane systematic reviews.

BACKGROUND: Childhood overweight and obesity are associated with adverse physical, social, and psychological outcomes. OBJECTIVES: We conducted an overview of Cochrane systematic reviews on the effectiveness and risks of interventions to treat overweight and obesity in children and adolescents. METHODS: In June 2019, we searched the Cochrane Database of Systematic Reviews for eligible reviews. The primary outcomes were change in adiposity (body mass and body mass index [BMI] z-score) and adverse events. Two reviewers screened studies and one reviewer extracted and another verified data. Two reviewers assessed methodological quality and reached consensus. Data were synthesized narratively. RESULTS: We included seven Cochrane reviews published between 2011 and 2017 containing evidence from 167 randomized controlled trials with 21,050 participants. Lifestyle and behavioural interventions more effectively reduced weight compared with no intervention, usual care, or another behavioural treatment (three reviews, low-to-moderate certainty). Parent-child lifestyle and behavioural interventions more effectively reduced BMI z-score compared with no intervention (one review, low certainty). Decision support tools for healthcare providers more effectively limited increases in BMI z-score compared with usual care (one review, moderate certainty). Pharmacologic treatments combined with behavioural modification more effectively reduced adiposity compared with placebo or usual care (one review, low certainty), but the risk of adverse events was greater than non-pharmacologic therapy. Surgical interventions (e.g., LAP-BAND) combined with behavioural modification more effectively reduced adiposity compared with behavioural modification alone (one review, low certainty). Those who underwent surgery reported a higher number of adverse events compared with those treated with lifestyle modification. CONCLUSIONS: There is low-certainty evidence that lifestyle and behavioural interventions, pharmacologic interventions, and surgical interventions are effective in weight management for children with overweight and obesity. Safety data remain lacking across all intervention modalities. Future research should focus on implementation strategies. Further, a focus on overall well-being may be more beneficial than weight management specifically.