Reporting of equity in observational epidemiology: A methodological review.

Background: Observational studies can inform how we understand and address persisting health inequities through the collection, reporting and analysis of health equity factors. However, the extent to which the analysis and reporting of equity-relevant aspects in observational research are generally unknown. Thus, we aimed to systematically evaluate how equity-relevant observational studies reported equity considerations in the study design and analyses. Methods: We searched MEDLINE for health equity-relevant observational studies from January 2020 to March 2022, resulting in 16 828 articles. We randomly selected 320 studies, ensuring a balance in focus on populations experiencing inequities, country income settings, and coronavirus disease 2019 (COVID-19) topic. We extracted information on study design and analysis methods. Results: The bulk of the studies were conducted in North America (n = 95, 30%), followed by Europe and Central Asia (n = 55, 17%). Half of the studies (n = 171, 53%) addressed general health and well-being, while 49 (15%) focused on mental health conditions. Two-thirds of the studies (n = 220, 69%) were cross-sectional. Eight (3%) engaged with populations experiencing inequities, while 22 (29%) adapted recruitment methods to reach these populations. Further, 67 studies (21%) examined interaction effects primarily related to race or ethnicity (48%). Two-thirds of the studies (72%) adjusted for characteristics associated with inequities, and 18 studies (6%) used flow diagrams to depict how populations experiencing inequities progressed throughout the studies. Conclusions: Despite over 80% of the equity-focused observational studies providing a rationale for a focus on health equity, reporting of study design features relevant to health equity ranged from 0-95%, with over half of the items reported by less than one-quarter of studies. This methodological study is a baseline assessment to inform the development of an equity-focussed reporting guideline for observational studies as an extension of the well-known Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guideline.

Troponin Structural Dynamics in the Native Cardiac Thin Filament Revealed by Cryo Electron Microscopy.

Cardiac muscle contraction occurs due to repetitive interactions between myosin thick and actin thin filaments (TF) regulated by Ca2+ levels, active cross-bridges, and cardiac myosin-binding protein C (cMyBP-C). The cardiac TF (cTF) has two nonequivalent strands, each comprised of actin, tropomyosin (Tm), and troponin (Tn). Tn shifts Tm away from myosin-binding sites on actin at elevated Ca2+ levels to allow formation of force-producing actomyosin cross-bridges. The Tn complex is comprised of three distinct polypeptides - Ca2+-binding TnC, inhibitory TnI, and Tm-binding TnT. The molecular mechanism of their collective action is unresolved due to lack of comprehensive structural information on Tn region of cTF. C1 domain of cMyBP-C activates cTF in the absence of Ca2+ to the same extent as rigor myosin. Here we used cryo-EM of native cTFs to show that cTF Tn core adopts multiple structural conformations at high and low Ca2+ levels and that the two strands are structurally distinct. At high Ca2+ levels, cTF is not entirely activated by Ca2+ but exists in either partially or fully activated state. Complete dissociation of TnI C-terminus is required for full activation. In presence of cMyBP-C C1 domain, Tn core adopts a fully activated conformation, even in absence of Ca2+. Our data provide a structural description for the requirement of myosin to fully activate cTFs and explain increased affinity of TnC to Ca2+ in presence of active cross-bridges. We suggest that allosteric coupling between Tn subunits and Tm is required to control actomyosin interactions.

Effectiveness of road safety interventions: An evidence and gap map.

Background: Road Traffic injuries (RTI) are among the top ten leading causes of death in the world resulting in 1.35 million deaths every year, about 93% of which occur in low- and middle-income countries (LMICs). Despite several global resolutions to reduce traffic injuries, they have continued to grow in many countries. Many high-income countries have successfully reduced RTI by using a public health approach and implementing evidence-based interventions. As many LMICs develop their highway infrastructure, adopting a similar scientific approach towards road safety is crucial. The evidence also needs to be evaluated to assess external validity because measures that have worked in high-income countries may not translate equally well to other contexts. An evidence gap map for RTI is the first step towards understanding what evidence is available, from where, and the key gaps in knowledge. Objectives: The objective of this evidence gap map (EGM) is to identify existing evidence from all effectiveness studies and systematic reviews related to road safety interventions. In addition, the EGM identifies gaps in evidence where new primary studies and systematic reviews could add value. This will help direct future research and discussions based on systematic evidence towards the approaches and interventions which are most effective in the road safety sector. This could enable the generation of evidence for informing policy at global, regional or national levels. Search Methods: The EGM includes systematic reviews and impact evaluations assessing the effect of interventions for RTI reported in academic databases, organization websites, and grey literature sources. The studies were searched up to December 2019. Selection Criteria: The interventions were divided into five broad categories: (a) human factors (e.g., enforcement or road user education), (b) road design, infrastructure and traffic control, (c) legal and institutional framework, (d) post-crash pre-hospital care, and (e) vehicle factors (except car design for occupant protection) and protective devices. Included studies reported two primary outcomes: fatal crashes and non-fatal injury crashes; and four intermediate outcomes: change in use of seat belts, change in use of helmets, change in speed, and change in alcohol/drug use. Studies were excluded if they did not report injury or fatality as one of the outcomes. Data Collection and Analysis: The EGM is presented in the form of a matrix with two primary dimensions: interventions (rows) and outcomes (columns). Additional dimensions are country income groups, region, quality level for systematic reviews, type of study design used (e.g., case-control), type of road user studied (e.g., pedestrian, cyclists), age groups, and road type. The EGM is available online where the matrix of interventions and outcomes can be filtered by one or more dimensions. The webpage includes a bibliography of the selected studies and titles and abstracts available for preview. Quality appraisal for systematic reviews was conducted using a critical appraisal tool for systematic reviews, AMSTAR 2. Main Results: The EGM identified 1859 studies of which 322 were systematic reviews, 7 were protocol studies and 1530 were impact evaluations. Some studies included more than one intervention, outcome, study method, or study region. The studies were distributed among intervention categories as: human factors (n = 771), road design, infrastructure and traffic control (n = 661), legal and institutional framework (n = 424), post-crash pre-hospital care (n = 118) and vehicle factors and protective devices (n = 111). Fatal crashes as outcomes were reported in 1414 records and non-fatal injury crashes in 1252 records. Among the four intermediate outcomes, speed was most commonly reported (n = 298) followed by alcohol (n = 206), use of seatbelts (n = 167), and use of helmets (n = 66). Ninety-six percent of the studies were reported from high-income countries (HIC), 4.5% from upper-middle-income countries, and only 1.4% from lower-middle and low-income countries. There were 25 systematic reviews of high quality, 4 of moderate quality, and 293 of low quality. Authors' Conclusions: The EGM shows that the distribution of available road safety evidence is skewed across the world. A vast majority of the literature is from HICs. In contrast, only a small fraction of the literature reports on the many LMICs that are fast expanding their road infrastructure, experiencing rapid changes in traffic patterns, and witnessing growth in road injuries. This bias in literature explains why many interventions that are of high importance in the context of LMICs remain poorly studied. Besides, many interventions that have been tested only in HICs may not work equally effectively in LMICs. Another important finding was that a large majority of systematic reviews are of low quality. The scarcity of evidence on many important interventions and lack of good quality evidence-synthesis have significant implications for future road safety research and practice in LMICs. The EGM presented here will help identify priority areas for researchers, while directing practitioners and policy makers towards proven interventions.

Effect of the N-terminal extension in myosin essential light chain A1 on the mechanism of actomyosin ATP hydrolysis.

Myosin essential light chains A1 and A2 are identical isoforms except for an extension of ∼40 amino acids at the N terminus of A1 that binds F-actin. The extension has no bearing on the burst hydrolysis rate (M-ATP → M-ADP-Pi) as determined by chemical quench flow (100 µM isoenzyme). Whereas actomyosin-S1A2 steady state MgATPase (low ionic strength, 20 °C) is hyperbolically dependent on concentration: Vmax 7.6 s-1, Kapp 6.4 µM (F-actin) and Vmax 10.1 s-1, Kapp 5.5 µM (native thin filaments, pCa 4), the relationship for myosin-S1A1 is bimodal; an initial rise at low concentration followed by a decline to one-third the Vmax of S1A2, indicative of more than one rate-limiting step and A1-enforced flux through the slower actomyosin-limited hydrolysis pathway. In double-mixing stopped-flow with an indicator, Ca(II)-mediated activation of Pi dissociation (regulatedAM-ADP-Pi → regulatedAM-ADP + Pi) is attenuated by A1 attachment to thin filaments (pCa 4). The maximum accelerated rates of Pi dissociation are: 81 s-1 (S1A1, Kapp 8.9 µM) versus 129 s-1 (S1A2, Kapp 58 µM). To investigate apomyosin-S1-mediated activation, thin filaments (EGTA) are premixed with a given isomyosin-S1 and double-mixing is repeated with myosin-S1A1 in the first mix. Similar maximum rates of Pi dissociation are observed, 44.5 s-1 (S1A1) and 47.1 s-1 (S1A2), which are lower than for Ca(II) activation. Overall, these results biochemically demonstrate how the longer light chain A1 can contribute to slower contraction and higher force and the shorter version A2 to faster contraction and lower force, consistent with their distribution in different types of striated muscle.

PROTOCOL: Effectiveness of economic development interventions in humanitarian settings in low- and middle-income countries: A mixed-method systematic review.

This is the protocol for a Campbell systematic review. The review will address the following research questions: (1) What are the effects of economic development interventions on the economic outcomes of people in humanitarian settings? What factors explain any observed variations in effect such as setting, programme design features or duration? (2) What are the effects of economic development interventions on the food security, nutrition, the psychosocial and mental health, and the physical health outcomes of populations in humanitarian settings? (3) What are the success factors and barriers that affect the implementation and effectiveness of economic development interventions on populations affected by humanitarian crisis?

PROTOCOL: Effects of interventions to improve access to financial services for micro-, small- and medium-sized enterprises in low- and middle-income countries: An evidence and gap map.

Background: Micro-, small-, and medium-sized enterprises (MSMEs) account for the vast majority of firms in most economies, particularly in developing nations, and are key contributors to job creation and global economic development. However, the most significant impediment to MSME development in low- and middle-income countries is a lack of access to both investment and working capital financing. Due to a lack of essential track record, appropriate collateral, and credit history, MSMEs are frequently denied business loans by traditional lending institutions. In addition, SMEs' inability to access funding is hindered by institutional, structural, and non-financial factors. To address this, both the public and private sectors employ indirect and direct finance interventions to help MSMEs in developing and emerging economies enhance and increase their financing needs. Given the importance of MSMEs in the economy, a comprehensive overview of and systematic synthesizing of the evidence of the effects of financial access interventions for MSMEs, capturing a wide variety of outcome variables, is useful. Objectives: The objective of this evidence and gap map (EGM) is to describe the existing evidence on the effects of various interventions dedicated to supporting and improving MSMEs' access to credit, as well as the corresponding firm performance and/or welfare outcomes. Methods: An EGM is a systematic evidence product that displays the existing evidence relevant to a specific research question. An EGM's end product is a research article or report, but it can also be shared via an interactive map drawn as a matrix of included studies and their corresponding interventions and outcomes. Interventions in low- and middle-income countries that target specific population subgroups are included on the map. The EGM considers five types of interventions: (i) strategy, legislation and regulatory; (ii) systems and institutions; (iii) facilitate access; (iv) lending instruments or financial products; and (v) demand-side interventions. The map, on the other hand, covers outcome domains for policy environment, financial inclusion, firm performance, and welfare. Impact evaluations or systematic reviews of relevant interventions for a previously defined target population are included in the EGM. Studies using experimental or non-experimental designs, as well as systematic reviews, are eligible. The EGM excludes before-and-after study designs with no suitable comparison group. Furthermore, the map excludes literature reviews, key informant interviews, focus group discussions, and descriptive analyses. Search strings were used to conduct electronic searches in databases. To ensure that the research team had identified a significant portion of relevant research works, the search strategy was supplemented with gray literature searches and systematic review citation tracking. We have compiled studies that are either completed or in progress. For practical reasons, studies are limited to papers written in English and are not restricted by publication date. Selection Criteria: We included studies that examined interventions to enhance MSMEs' access to finance in low- and middle-income countries targeting MSMEs including households, smallholder farmers and single person enterprise as well as financial institutions/agencies and their staff. The EGM considers five types of interventions that aim to: (i) deliver strategy, legislation, and regulatory aspects; (ii) systems and institutions that enable financing; (iii) facilitate access to finance; (iv) deliver different lending instruments or financial products, including traditional forms of microcredit; and (v) demand-side interventions such as programs on financial literacy. The map includes outcome domains surrounding policy environment, financial inclusion, firm performance, and welfare. Eligible studies must be experimental, non-experimental, or systematic reviews. In addition, the study designs must have a suitable comparison group before and after the implementation of interventions. Results: The EGM includes 413 studies. The majority of the studies (379 studies) analyzed microenterprises, such as households and smallholder farmers; 7 studies analyzed community groups; while 109 studies analyzed small and medium enterprises. There were 147 studies on interventions that targeted multiple firm sizes. Lending instruments/financial products are the most common intervention across all firm types. When it comes to the types of firms that receive the said financial intervention, the data is overwhelmingly in favor of microenterprises (278 studies), followed by systems and organizations (138 studies) that support better access to such financial products and services. Welfare outcomes have the most evidence out of all of the outcomes of interest, followed by firm performance and financial inclusion. Among all firm types, welfare outcomes are primarily targeted at microenterprises. With 59 studies, we can say that small businesses have a significantly large number of enterprise performance outcomes. of the 413 studies, 243 used non-experimental or quasi-experimental designs (mainly propensity score matching and instrumental variable approaches), 136 used experimental methods, and 34 were systematic reviews. 175 studies (43%) provided evidence from Sub-Saharan Africa, 142 studies (35%) from South Asia, 86 studies (21%) from East Asia and the Pacific, 66 studies (16%) from Latin America and the Caribbean, 28 studies (7%), Europe and Central Asia, and 21 studies (5%) from the Middle East and North Africa. Most of the included evidence covers low-income (26%) and lower-middle income countries (66%), and to a lesser extent upper-middle-income countries (26%). Conclusion: This map depicts the existing evidence and gaps on the effects of interventions to enhance MSMEs' access to financial services in low and middle-income countries. Interventions directed at microenterprises with welfare outcomes have a significant number of research outcomes in the literature. SME evaluations have looked at firm performance, with less focus to employment and the welfare effects on owners and employees, including poverty reduction. Microcredit/loans have been the focus of a large number of research papers (238 studies), indicating the field's growing popularity. However, emerging financial interventions such as facilitating access to digital financial services are relatively under-studied. Several studies also investigate rural or population in remote areas with 192 studies, 126 studies on poor and disadvantaged, and 114 papers on women. Most of the research is conducted in Sub-Saharan Africa (175 studies) and South Asia (142 studies) so further research in other regions could be conducted to allow a more holistic understanding of the effects of financial inclusion interventions. Credit lines, supply chain finance, and trade financing, which are some of the ADB's financial tools have limited evidence. Future studies should look into strategy, law, and regulation interventions, as well as interventions targeted at SMEs, and examine policy and regulatory environment outcomes as well as welfare outcomes. Interventions on the demand side and their impact on the policy and regulatory environment, as well as facilitating access are relatively understudied.

PROTOCOL: The impact of agricultural mechanisation on women's economic empowerment: A mixed-methods systematic review.

This is the protocol for a Campbell systematic review. The main objective of the review is to answer the following questions: What is the impact of mechanisation on agriculture? What is the impact of mechanisation on women's economic empowerment? The study will review the impact of mechanisation on labour demand and supply, land and labour productivity, farmers' incomes, health and women's empowerment. All literature will be considered, including nonintervention studies and studies not reporting gender-disaggregated results.

PROTOCOL: Value chain interventions for improving women's economic empowerment: A mixed-method systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows: The primary objective of this review is to understand as well as evaluate what approaches, strategies or interventions focused on women's engagement in agricultural value chains and markets that have led to women's economic empowerment in low-and-middle-income countries. The secondary objective of this review is to examine in which contexts are these approaches effective (or ineffective)? What are the contextual barriers and facilitators, determining the participation of women in, and benefits from, engagement in the value chain in low-and middle-income countries programme effectiveness. Finally, this review aims to refine the theory of change that describes how value chain interventions lead to women's economic empowerment using evidence drawn from both rigorous quantitative impact evaluation studies and qualitative studies.

Effectiveness of interventions for improving social inclusion outcomes for people with disabilities in low- and middle-income countries: A systematic review.

Background: People with disabilities-more than a billion people worldwide-are frequently excluded from social and political life, and often experience stigmatising attitudes and behaviours from people without disabilities. This stigma, coupled with inaccessible environments and systems and institutional barriers (e.g., lack of inclusive legislation), may result in discrimination against people with disabilities (and their families) to the degree that they are not able to enjoy their rights on an equal basis with others. Objectives: This review examines the effectiveness of interventions for improving social inclusion outcomes (acquisition of skills for social inclusion, broad-based social inclusion, and improved relationships) for people with disabilities in low- and middle-income countries (LMICs). Search Methods: We searched academic and online databases, carried out citation tracking of included studies, and contacted experts to ensure our search was as comprehensive as possible. We also ran the searches with search terms specific to social inclusion review using Open Alex in EPPI reviewer. Selection Criteria: We included all studies which reported on impact evaluations of interventions to improve social inclusion outcomes for people with disabilities in LMIC. Data Collection and Analysis: We used review management software EPPI Reviewer to screen the search results. Two review authors independently extracted the data from each study report, including for the confidence in study findings appraisal. Data and information were extracted regarding available characteristics of participants, intervention characteristics and control conditions, research design, sample size, risk of bias and outcomes, and results. Random-effects inverse variance weighted meta-analytic methods were used to synthesise standardised mean differences for the outcomes. Main Results: We identified 37 experimental and quasi-experimental studies. Studies were conducted in 16 countries, with the majority of the included studies (n = 13) from South Asia and nine each from East Asia, the Pacific, the Middle East, and North Africa. Most studies targeted children with disabilities (n = 23), and 12 targeted adults with disabilities. Most focused on people with intellectual disabilities (n = 20) and psychosocial disabilities (n = 13). Regarding intervention content, most (n = 17) of the included programmes aimed to improve the social and communication skills of people with disabilities through social skills training programmes. Ten studies aimed at providing personal assistance and support and evaluated the effects of a parent training programme on the interactive skills of parents of children and their children with disabilities. We calculated effect sizes from experimental and quasi-experimental studies for outcomes on skills for social inclusion, relationships of people with disabilities with family and community members, and broad-based social inclusion among people with disabilities. A meta-analysis of 16 studies indicates an overall positive, statistically significant and large effect of the interventions for skills for social inclusion with standardised mean difference (SMD) = 0.87, confidence interval (CI) = 0.57 to 1.16, k = 26, I 2 = 77%, p < 0.001). For relationships across 12 studies, we find a positive but moderate effect (SMD = 0.61, CI = 0.41 to 0.80, k = 15, I 2 = 64%, p < 0.01). As for the overall effect on broad-based social inclusion, we find the average effect size was large, and there was significant dispersion across studies (SMD = 0.72, CI = 0.33 to 1.11, k = 2, I 2 = 93%, p < 0.01). Despite the significant and large effects estimated by the studies, some limitations must be noted. Although there was a consensus on the direction of the effects, the studies presented considerable heterogeneity in the size of the effects. A majority (n = 27) of studies were assessed to be of low confidence related to methodological limitations, so the findings must be interpreted with caution. Tests for publication bias show that the effect sizes of social skills (p < 0.01) and social inclusion (p = 0.01) are all likely to be inflated by the existence of the publication bias. Authors' Conclusions: The review's findings suggest that various interventions to improve the social inclusion of people with disabilities have a significant positive effect. Interventions such as social and communication training and personal assistance led to significant improvement in the social behaviour and social skills of people with disabilities. Studies targeting broad-based social inclusion showed a large and significant positive effect. A moderate effect was reported from interventions designed to improve relationships between people with disabilities and their families and communities. However, the findings of this review must be interpreted cautiously, given the low confidence in study methods, severe heterogeneity and significant publication bias. The available evidence focused primarily on individual-level barriers such as interventions for improving social or communications skills of people with disabilities and not the systemic drivers of exclusions such as addressing societal barriers to inclusion, such as stigma reduction, and interventions to strengthen legislation, infrastructure, and institutions.

Mapping reviews, scoping reviews, and evidence and gap maps (EGMs): the same but different- the "Big Picture" review family.

Scoping reviews, mapping reviews, and evidence and gap maps are evidence synthesis methodologies that address broad research questions, aiming to describe a bigger picture rather than address a specific question about intervention effectiveness. They are being increasingly used to support a range of purposes including guiding research priorities and decision making. There is however a confusing array of terminology used to describe these different approaches. In this commentary, we aim to describe where there are differences in terminology and where this equates to differences in meaning. We demonstrate the different theoretical routes that underpin these differences. We suggest ways in which the approaches of scoping and mapping reviews may differ in order to guide consistency in reporting and method. We propose that mapping and scoping reviews and evidence and gap maps have similarities that unite them as a group but also have unique differences. Understanding these similarities and differences is important for informing the development of methods used to undertake and report these types of evidence synthesis.

PROTOCOL: Treatment for depressive disorder among adults: An evidence and gap map of systematic reviews.

This is the protocol for a Campbell evidence and gap map. The objective of the map is to map available systematic reviews on the effectiveness of treatments for depressive disorders among adults. Specifically, this EGM includes studies on the effectiveness of treatments across a range of outcome domains.

PROTOCOL: An evidence and gap map of studies of implementation issues for interventions for those affected by and at risk of homelessness in high-income countries.

This is the protocol for a Campbell systematic review. The objectives are as follows. The proposed evidence and gap map will present relevant process evaluations and other studies of barriers and facilitators, both qualitative and quantitative, for eligible homelessness interventions to highlight the issues arising in the implementation of these interventions. Specifically, the objectives of the map are to: (i) develop a clear taxonomy of interventions and implementation issues (e.g., barriers and facilitators-factors which works as barriers to hinder successful implementation of policies and programmes and factors which facilitate the intervention and therefore support its implementation) related to homelessness in high-income countries; (ii) map available systematic reviews and primary studies of the implementation issues of interventions for those experiencing homelessness and those at risk of homelessness, with an overview provided in a summary report; (iii) provide a searchable database of included studies accessible to research users via CHI website.

High-resolution cryo-EM structure of the junction region of the native cardiac thin filament in relaxed state.

Cardiac contraction depends on molecular interactions among sarcomeric proteins coordinated by the rising and falling intracellular Ca2+ levels. Cardiac thin filament (cTF) consists of two strands composed of actin, tropomyosin (Tm), and equally spaced troponin (Tn) complexes forming regulatory units. Tn binds Ca2+ to move Tm strand away from myosin-binding sites on actin to enable actomyosin cross-bridges required for force generation. The Tn complex has three subunits-Ca2+-binding TnC, inhibitory TnI, and Tm-binding TnT. Tm strand is comprised of adjacent Tm molecules that overlap "head-to-tail" along the actin filament. The N-terminus of TnT (e.g., TnT1) binds to the Tm overlap region to form the cTF junction region-the region that connects adjacent regulatory units and confers to cTF internal cooperativity. Numerous studies have predicted interactions among actin, Tm, and TnT1 within the junction region, although a direct structural description of the cTF junction region awaited completion. Here, we report a 3.8 Å resolution cryo-EM structure of the native cTF junction region at relaxing (pCa 8) Ca2+ conditions. We provide novel insights into the "head-to-tail" interactions between adjacent Tm molecules and interactions between the Tm junction with F-actin. We demonstrate how TnT1 stabilizes the Tm overlap region via its interactions with the Tm C- and N-termini and actin. Our data show that TnT1 works as a joint that anchors the Tm overlap region to actin, which stabilizes the relaxed state of the cTF. Our structure provides insight into the molecular basis of cardiac diseases caused by missense mutations in TnT1.

Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament.

Cardiac myosin binding protein C (cMyBP-C) modulates cardiac contraction via direct interactions with cardiac thick (myosin) and thin (actin) filaments (cTFs). While its C-terminal domains (e.g. C8-C10) anchor cMyBP-C to the backbone of the thick filament, its N-terminal domains (NTDs) (e.g. C0, C1, M, and C2) bind to both myosin and actin to accomplish its dual roles of inhibiting thick filaments and activating cTFs. While the positions of C0, C1 and C2 on cTF have been reported, the binding site of the M-domain on the surface of the cTF is unknown. Here, we used cryo-EM to reveal that the M-domain interacts with actin via helix 3 of its ordered tri-helix bundle region, while the unstructured part of the M-domain does not maintain extensive interactions with actin. We combined the recently obtained structure of the cTF with the positions of all the four NTDs on its surface to propose a complete model of the NTD binding to the cTF. The model predicts that the interactions of the NTDs with the cTF depend on the activation state of the cTF. At the peak of systole, when bound to the extensively activated cTF, NTDs would inhibit actomyosin interactions. In contrast, at falling Ca2+ levels, NTDs would not compete with the myosin heads for binding to the cTF, but would rather promote formation of active cross-bridges at the adjacent regulatory units located at the opposite cTF strand. Our structural data provides a testable model of the cTF regulation by the cMyBP-C.

PROTOCOL: Critical appraisal of methodological quality and reporting items of systematic reviews with meta-analysis in evidence-based social science in China: A systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows: (1) To evaluate the reporting quality of systematic reviews published in Chinese social science journals against the PRISMA and MOOSE standards; (2) To evaluate the methodology quality of systematic reviews published in Chinese social science journals against the AMSTAR-2 and DART standards; and (3) To analyze other characteristics of systematic reviews published in Chinese social science journals using content analysis.

PROTOCOL: The effectiveness, implementation and cost effectiveness of mentoring programmes in reducing anti-social, violent and offending behaviour in children aged 17 years and below: A mixed method systematic review.

This is the protocol for a Campbell systematic review. The review will address the following research questions: What is the evidence on the effects of adult mentoring programmes in reducing anti-social, violent and offending behaviour in children aged under 18 years? Are these effects sustained after the end of mentoring? Which aspects/features of adult mentoring programmes promote the reduction of anti-social, violent and criminal behaviour in children aged under 18 years? What are the hindering factors/barriers that affect the successful implementation of adult mentoring programmes in children aged under 18 years? What are the supporting factors/facilitators that contribute to the successful implementation of adult mentoring programmes in children aged under 18 years? What is the evidence on programme costs and incremental cost effectiveness? (The incremental (or marginal cost) is the cost of providing the intervention over and above the cost of usual services).