The Role of Licorice Chalcones as Molecular Genes and Signaling Pathways Modulator-A Review of Experimental Implications for Nicotine-Induced Non-Small Cell Lung Cancer Treatment.

Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation of the nicotinic acetylcholine receptor (α7nAChR)-mediated cell-signaling pathways and molecular genes involved in proliferation, angiogenesis, and metastasis. Chalcones (CHs) and their derivatives are intermediate plant metabolites involved in flavonol biosynthesis. Isoliquiritigenin (ILTG), licochalcone A-E (LicoA-E), and echinatin (ECH) are the most common natural CHs isolated from the root of Glycyrrhiza (also known as licorice). In vitro and/or vivo experiments have shown that licorice CHs treatment exhibits a range of pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. Despite advances in NSCLC treatment, the mechanisms of licorice CHs in nicotine-induced NSCLC treatment remain unknown. Therefore, the aim of this paper is to review experimental studies through the PubMed/Medline database that reveal the effects of licorice CHs and their potential mechanisms in nicotine-induced NSCLC treatment.

Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.

INTRODUCTION: Experimental studies in animals have yielded conflicting results on the role of Tumor Necrosis Factor (TNF) in sepsis and endotoxemia, with some reporting adaptive and others inappropriate effects. A meta-analysis of the available literature was performed to determine the factors explaining this discrepancy. METHODS: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered with PROSPERO (CRD42020167384) prior to data collection. PubMed and Embase were the databases queried. Risk of bias was evaluated using the SYRCLE Risk of Bias Tool. All animal studies investigating sepsis-related mortality and modified TNF signaling were considered eligible. The exclusion criteria were: lack of mortality data, 7-day mortality rates below 10% in both wild type and TNF-altered pathway animals, and absence of an English abstract. To determine the role of TNF according to the experimental protocol, three approaches were used: first an approach based on the statistical significance of each experiment, then the pooled mortality was calculated, and finally the weighted risk ratio for mortality was assessed. RESULTS: A total of 175 studies were included in the analysis, comprising a total of 760 experiments and involving 19,899 animals. The main species used were mice (77%) and rats (21%). The most common method of TNF pathway modulation was TNF pathway inactivation that was primarily associated with an inappropriate secretion of TNF. At the opposite, TNF injection was associated with an adaptive role of TNF. Lipopolysaccharide (LPS) injection was the most used stimulus to establish an infectious model (42%) and was strongly associated with an inappropriate role of TNF. Conversely, live bacterial models, especially the cecal ligation and puncture (CLP) model, pneumonia, meningitis, and gastrointestinal infection, were associated with an adaptive role. This was particularly evident for Listeria monocytogenes, Streptococcus pneumoniae. CONCLUSION: The role of TNF during infection varies depending on the experimental model used. Models that mimic clinical conditions, based on virulent bacteria that cause high mortality even at low inocula, demonstrated an adaptive role of TNF. Conversely, models based on LPS or low-pathogenic live bacteria, administered at doses well above physiological thresholds and combined with early antibiotic therapy, were associated with an inappropriate role.

Using a novel 'difference-in-differences' method and syndromic surveillance to estimate the change in local healthcare utilisation during periods of media reporting in the early stages of the COVID-19 pandemic in England.

OBJECTIVES: Syndromic surveillance supplements traditional laboratory reporting for infectious diseases monitoring. Prior to widespread COVID-19 community surveillance, syndromic surveillance was one of several systems providing real-time information on changes in healthcare-seeking behaviour. The study objective was to identify changes in healthcare utilisation during periods of high local media reporting in England using 'difference-in-differences' (DiD). STUDY DESIGN: A retrospective observational study was conducted using five media events in January-February 2020 in England on four routinely monitored syndromic surveillance indicators. METHODS: Dates 'exposed' to a media event were estimated using Google Trends internet search intensity data (terms = 'coronavirus' and local authority [LA]). We constructed a negative-binomial regression model for each indicator and event time period to estimate a direct effect. RESULTS: We estimated a four-fold increase in telehealth 'cough' calls and a 1.4-fold increase in emergency department (ED) attendances for acute respiratory illness in Brighton and Hove, when a so-called 'superspreading event' in this location was reported in local and national media. Significant decreases were observed in the Buxton (telehealth and ED attendance) and Wirral (ED attendance) areas during media reports of a returnee from an outbreak abroad and a quarantine site opening in the area respectively. CONCLUSIONS: We used a novel approach to directly estimate changes in syndromic surveillance reporting during the early phase of the COVID-19 pandemic in England, providing contextual information on the interpretation of changes in health indicators. With careful consideration of event timings, DiD is useful in producing real-time estimates on specific indicators for informing public health action.

Mutual Aid Groups for Loneliness, Psychosocial Disability, and Continuity of Care.

The objective of the present study was to evaluate the effectiveness of mutual help groups in continuity of care, loneliness and psychosocial disability in a Colombian context. For this, a quasi-experimental design is used, with pre- and post-intervention assessments due to non-randomized participant allocation. The study involved 131 individuals with mental disorders. The Psychosocial Disability Scale, The Alberta Scale of Continuity of Services in Mental Health, the UCLA Scale and the Zarit Caregiver Burden Scale were employed. The intervention was based on the core components of mutual aid groups. Significant differences (p < 0.001) were observed for the study variables, particularly in Loneliness, Continuity of Care, and various domains of psychosocial disability. A large effect size was found for these variables after the intervention. Most variables exhibited a moderate to large effect. This study demonstrates the effectiveness of mutual groups facilitated by mental health personnel at the primary care level.

The effect of the 2009 revised U.S. guidelines for gestational weight gain on maternal and infant health: a quasi-experimental study.

BACKGROUND: Excess gestational weight gain (GWG) has adverse short- and long-term effects on the health of mothers and infants. In 2009, the US Institute of Medicine revised its guidelines for GWG and reduced the recommended GWG for women who are obese. There is limited evidence on whether these revised guidelines affected GWG and downstream maternal and infant outcomes. METHODS: We used data from the 2004-2019 waves of the Pregnancy Risk Assessment Monitoring System, a serial cross-sectional national dataset including over 20 states. We conducted a quasi-experimental difference-in-differences analysis to assess pre/post changes in maternal and infant outcomes among women who were obese, while "differencing out" the pre/post changes among a control group of women who were overweight. Maternal outcomes included GWG and gestational diabetes; infant outcomes included preterm birth (PTB), low birthweight (LBW), and very low birthweight (VLBW). Analysis began in March 2021. RESULTS: There was no association between the revised guidelines and GWG or gestational diabetes. The revised guidelines were associated with reduced PTB (- 1.19% points, 95%CI: - 1.86, - 0.52), LBW (- 1.38% points 95%CI: - 2.07, - 0.70), and VLBW (- 1.30% points, 95%CI: - 1.68, - 0.92). Results were robust to several sensitivity analyses. CONCLUSION: The revised 2009 GWG guidelines were not associated with changes in GWG or gestational diabetes but were associated with improvements in infant birth outcomes. These findings will help inform further programs and policies aimed at improving maternal and infant health by addressing weight gain in pregnancy.

Traditional medicinal plants in the treatment of gastrointestinal parasites in humans: A systematic review and meta-analysis of clinical and experimental evidence.

Gastrointestinal (GI) parasites cause significant morbidity and mortality worldwide. The use of conventional antiparasitic drugs is often inhibited due to limited availability, side effects or parasite resistance. Medicinal plants can be used as alternatives or adjuncts to current antiparasitic therapies. This systematic review and meta-analysis aimed to critically synthesise the literature on the efficacy of different plants and plant compounds against common human GI parasites and their toxicity profiles. Searches were conducted from inception to September 2021. Of 5393 screened articles, 162 were included in the qualitative synthesis (159 experimental studies and three randomised control trials [RCTs]), and three articles were included in meta-analyses. A total of 507 plant species belonging to 126 families were tested against different parasites, and most of these (78.4%) evaluated antiparasitic efficacy in vitro. A total of 91 plant species and 34 compounds were reported as having significant in vitro efficacy against parasites. Only a few plants (n = 57) were evaluated for their toxicity before testing their antiparasitic effects. The meta-analyses revealed strong evidence of the effectiveness of Lepidium virginicum L. against Entamoeba histolytica with a pooled mean IC50 of 198.63 µg/mL (95% CI 155.54-241.72). We present summary tables and various recommendations to direct future research.

Effect of COVID-19 prevention as part of an urban renewal programme.

OBJECTIVES: To address existing inequalities, the Barcelona City Council launched a Neighbourhood Plan in 2016-2020. During the first wave of the COVID-19 pandemic, the Neighbourhood Plan interventions were intensified. This study aimed to assess the effect of the plan on the incidence of COVID-19 during the first wave of the pandemic in Barcelona. STUDY DESIGN: We used a quasi-experimental design with 16 intervention neighbourhoods and 17 neighbourhoods in the comparison group with similar socioeconomic characteristics. METHODS: We calculated the cumulative incidence rate (CIR) of COVID-19 per 100,000 inhabitants by sex, age groups, and neighbourhood of residence. Poisson regression models were fitted to estimate the crude relative risk and relative risk adjusted by socioeconomic status (cRR and aRR) and their 95% confidence intervals (CIs). RESULTS: The CIR of COVID-19 was lower in the intervention neighbourhoods (CIR: 841 per 100,000 inhabitants) than in the comparison group (CIR: 973 per 100,000 inhabitants). On multivariate analysis, the aRR was 0.77 (CI: 0.70-0.83) for men and 0.89 (CI: 0.83-0.96) for women. Among men older than 75 years (aRR = 0.73; CI: 0.62-0.86), statistically significant differences were found in the intervention neighbourhoods compared to the comparison group. This pattern was not observed in women older than 75 years (aRR = 1.13; CI: 0.99-1.30). CONCLUSION: This research finds positive short-term effect in the intervention neighbourhoods. We conclude that the COVID-19 control and prevention interventions are likely to explain the better performance in the neighbourhoods included in the Neighbourhood Plan.

Beneficial role of kaempferol and its derivatives from different plant sources on respiratory diseases in experimental models.

Respiratory illnesses impose a significant health burden and cause deaths worldwide. Despite many advanced strategies to improve patient outcomes, they are often less effective. There is still considerable room for improvement in the treatment of various respiratory diseases. In recent years, alternative medicinal agents derived from food plants have shown better beneficial effects against a wide variety of disease models, including cancer. In this regard, kaempferol (KMF) and its derivatives are the most commonly found dietary flavonols. They have been found to exhibit protective effects on multiple chronic diseases like diabetes, fibrosis, and so on. A few recent articles have reviewed the pharmacological actions of KMF in cancer, central nervous system diseases, and chronic inflammatory diseases. However, there is no comprehensive review that exists regarding the beneficial effects of KMF and its derivatives on both malignant- and non-malignant respiratory diseases. Many experimental studies reveal that KMF and its derivatives are helpful in managing a wide range of respiratory diseases, including acute lung injury, fibrosis, asthma, cancer, and chronic obstructive pulmonary disease, and their underlying molecular mechanisms. In addition, we also discussed the chemistry and sources, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, methods to enhance bioavailability, as well as our perspective on future research with KMF and its derivatives.

Minimum wiping pressure and number of wipes that can remove dirt during bed baths using disposable towels: a multi-study approach.

BACKGROUND: Friction irritation by wiping increases the risk of skin problems. In bed baths with cotton towels, wiping three times with weak pressure (10-20 mmHg ≈ 1333-2666 Pa) can remove dirt while maintaining skin barrier function. However, few studies have examined the appropriate frictional irritation with disposable towels. This study aimed to analyse the wiping pressure and number of wipes currently applied by nurses when using disposable towels during bed baths and propose the minimum values for removing dirt from the skin. METHODS: This multi-study approach consisted of cross-sectional and crossover design components. In Study 1, 101 nurses in two hospitals were observed by recording the wiping pressure and number of wipes when using both disposable (nonwoven) and cotton (woven) towels. Wiping pressure and number of wipes by towel materials were analysed using a linear mixed model. In Study 2, 50 adults received oily and aqueous dirt on their forearms, which were wiped six-times with disposable towels, applying randomly assigned pressure categories. We used colour image analysis and a linear mixed model to estimate the dirt removal rate for each combination of wiping pressure and number of wipes. RESULTS: Study 1 showed that although wiping pressure did not differ by towel material, the number of wipes was significantly higher for disposable wipes than cotton wipes. Approximately 5% of nurses applied strong wiping pressure or wiped too often. In Study 2, wiping three times with disposable towels at least 5-10 mmHg achieved dirt removal rates of ≥80%. CONCLUSIONS: Some nurses excessively wiped using disposable towels, which might cause skin problems. However, excessive wiping is not required to adequately remove dirt, regardless of the towel material used in various clinical situations. We recommend wiping at 10-20 mmHg of pressure (just like stroking gently) at least three times to improve the quality of bed baths. These findings highlight the need to develop skin-friendly bed bath educational programmes, particularly using appropriate frictional irritation to reduce the risk of skin problems.

Mechanistic Insight into Hydroboration of Imines from Combined Computational and Experimental Studies.

Boron Lewis acid-catalyzed and catalyst-free hydroboration reactions of imines are attractive due to the mild reaction conditions. In this work, the mechanistic details of the hydroboration reactions of two different kinds of imines with pinacolborane (HBpin) are investigated by combining density functional theory calculations and some experimental studies. For the hydroboration reaction of N-(α-methylbenzylidene)aniline catalyzed by tris[3,5-bis(trifluoromethyl)phenyl]borane (BArF 3 ), our calculations show that the reaction proceeds through a boron Lewis acid-promoted hydride transfer mechanism rather than the classical Lewis acid activation mechanism. For the catalyst- and solvent-free hydroboration reaction of imine, N-benzylideneaniline, our calculations and experimental studies indicate that this reaction is difficult to occur under the reaction conditions reported previously. With a combination of computational and experimental studies, we have established that the commercially available BH3 ⋅ SMe2 can serve as an efficient catalyst for the hydroboration reactions of N-benzylideneaniline and similar imines. The hydroboration reactions catalyzed by BH3 ⋅ SMe2 are most likely to proceed through a hydroboration/B-H/B-N σ-bond metathesis pathway, which is very different from that of the reaction catalyzed by BArF 3 .

The effect of the 2009 WIC revision on maternal and child health: A quasi-experimental study.

BACKGROUND: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is the largest U.S. nutrition program for low-income pregnant women. It was revised in 2009, with the goal of improving nutritional content of food packages, enhancing nutrition education, and strengthening breast feeding support. Few studies have assessed the effects of this revision on perinatal health. OBJECTIVES: To investigate the impact of the revised WIC program on maternal and child health in a large, multi-state data set. METHODS: We conducted a quasi-experimental difference-in-differences analysis, comparing the pre/post changes among WIC recipients to changes among non-recipients. We adjusted for key sociodemographic covariates in multivariable linear models. We used data from the Pregnancy Risk Assessment Monitoring System (PRAMS) for 18 states from 2004 to 2017. RESULTS: The main analysis included 331,946 mother-infant dyads. WIC recipients were more likely to be younger, Black or Hispanic/Latina, unmarried, and of greater parity. The revised WIC program was associated with reduced likelihood of more-than-recommended GWG (-1.29% points, 95% confidence interval [CI] -2.03, -0.56) and increased likelihood of ever breast fed (1.18% points, 95% CI 0.28, 2.08). We also identified heterogeneous effects on GWG, with more pronounced associations among women 35 and older. There were no associations with foetal growth. CONCLUSIONS: The revised WIC program was associated with improvements in women's gestational weight gain and infant breast feeding.

The impact of environmental and occupational exposures of manganese on pulmonary, hepatic, and renal functions.

Manganese (Mn) is an essential trace element for humans, but long-term environmental or occupational exposures can lead to numerous health problems. Although many studies have identified an association between Mn exposures and neurological abnormalities, emerging data suggest that occupationally and environmentally relevant levels of Mn may also be linked to multiple organ dysfunction in the general population. In this regard, many experimental and clinical studies provide support for a causal link between Mn exposure and structural and functional changes that are responsible for organ dysfunction in major organs like lung, liver, and kidney. The underlying mechanisms suggested to Mn toxicity include altered activities of the components of intracellular signaling cascades, oxidative stress, apoptosis, affected cell cycle regulation, autophagy, angiogenesis, and an inflammatory response. We further discussed the sources and possible mechanisms of Mn absorption and distribution in different organs. Finally, treatment strategies available for treating Mn toxicity as well as directions for future studies were discussed.

Climate impacts on organisms, ecosystems and human societies: integrating OCLTT into a wider context.

Physiological studies contribute to a cause and effect understanding of ecological patterns under climate change and identify the scope and limits of adaptation. Across most habitats, this requires analyzing organism responses to warming, which can be modified by other drivers such as acidification and oxygen loss in aquatic environments or excess humidity or drought on land. Experimental findings support the hypothesis that the width and temperature range of thermal performance curves relate to biogeographical range. Current warming causes range shifts, hypothesized to include constraints in aerobic power budget which in turn are elicited by limitations in oxygen supply capacity in relation to demand. Different metabolic scopes involved may set the borders of both the fundamental niche (at standard metabolic rate) and the realized niche (at routine rate). Relative scopes for aerobic performance also set the capacity of species to interact with others at the ecosystem level. Niche limits and widths are shifting and probably interdependent across life stages, with young adults being least thermally vulnerable. The principles of thermal tolerance and performance may also apply to endotherms including humans, their habitat and human society. Overall, phylogenetically based comparisons would need to consider the life cycle of species as well as organism functional properties across climate zones and time scales. This Review concludes with a perspective on how mechanism-based understanding allows scrutinizing often simplified modeling approaches projecting future climate impacts and risks for aquatic and terrestrial ecosystems. It also emphasizes the usefulness of a consensus-building process among experimentalists for better recognition in the climate debate.

In vitro investigation of biophysical interactions between Ag(I) complexes of bis(methyl)(thia/selena)salen and ct-DNA via multi-spectroscopic, physicochemical and molecular docking methods along with cytotoxicity study.

Four silver(I) (Ag(I)) complexes: 1.PF6 , 2.PF6 , 1.ClO4 and 2.ClO4 of bis(methyl)thia salen (1) and bis (methyl)selena salen (2) with two different counter anions (PF6 - and ClO4 - ) have been investigated for DNA binding properties. In vitro interactional association between the Ag(I) complexes and ct-DNA has been examined by performing spectroscopic titrations on absorption spectrophotometer and fluorescence spectrophotometer. A competitive binding study has also been done using a fluorescence spectrophotometer with ethidium bromide as a classical intercalator. The spectroscopic methods revealed a major groove. Viscometry and agarose gel electrophoresis experiments have also been performed as physicochemical methods to confirm the binding of complex molecules with DNA. Molecular docking analysis has been executed to obtain the theoretical insight into the mode of binding. The docking study demonstrated the major groove binding of all four complexes to the DNA with electrostatic metal-phosphate interactions (between the metal and the backbone of DNA) and hydrophobic interactions. Cytotoxicity of the complexes has been studied on the Human Fibroblast foreskin (HFF) cell line. The cytotoxicity results showed positive gesture for moving ahead to the next level of screening; the values were above 10 µM which are appreciated for the normal cell lines.

Study of a Controlled Piezoelectric Damper.

In this work an original construction of a vibration damper controlled by means of a valve with a short time of operation lag is presented. The valve-controlling properties of the damper regulates the flow of fluid between the chambers of the damper and was constructed using piezoelectric actuators, whose characteristic feature is the possibility to change dimensions, e.g., length, under the influence of voltage. As a result, by changing voltage it is possible to control the throttle of the flow by changing the width of a gap, which influences a change of damping forces. Such a solution enables a quicker change of damping forces than in other kinds of controlled damper. Due to the obtained properties, the damper may be applied to reduce the vibrations of vehicles and machines that undergo quick-change loads. In the article, the results of experimental studies of the aforementioned damper are presented. Based on the results, dissipative characteristics were determined. Also, results of numerical studies comprising the development of a numerical model of a controlled piezoelectric damper are shown. Results of numerical studies, as well as experimental studies, are presented in the form of dissipative characteristics. Comparison of results of numerical and experimental studies confirms the possibility to apply this kind of construction in semi-active systems of vibration reduction of vehicles and machines.

Role of Defect Engineering and Surface Functionalization in the Design of Carbon Nanotube-Based Nitrogen Oxide Sensors.

Nitrogen oxides (NOx) are among the main atmospheric pollutants; therefore, it is important to monitor and detect their presence in the atmosphere. To this end, low-dimensional carbon structures have been widely used as NOx sensors for their outstanding properties. In particular, carbon nanotubes (CNTs) have been widely used as toxic-gas sensors owing to their high specific surface area and excellent mechanical properties. Although pristine CNTs have shown promising performance for NOx detection, several strategies have been developed such as surface functionalization and defect engineering to improve the NOx sensing of pristine CNT-based sensors. Through these strategies, the sensing properties of modified CNTs toward NOx gases have been substantially improved. Therefore, in this review, we have analyzed the defect engineering and surface functionalization strategies used in the last decade to modify the sensitivity and the selectivity of CNTs to NOx. First, the different types of surface functionalization and defect engineering were reviewed. Thereafter, we analyzed experimental, theoretical, and coupled experimental-theoretical studies on CNTs modified through surface functionalization and defect engineering to improve the sensitivity and selectivity to NOx. Finally, we presented the conclusions and the future directions of modified CNTs as NOx sensors.

Corporate social responsibility in times of need: Community support during the COVID-19 pandemics.

Since the outbreak of COVID-19, the hotel sector has engaged in various corporate social responsibility (CSR) initiatives to show solidarity with local communities. Our research examines the impact of such initiatives on tourists' intentions to spread positive word-of-mouth (WOM) and their intentions to visit when the current pandemic ends. Our experimental results suggest community support in the form of providing free accommodation to homeless people increases tourists' intentions to spread positive WOM, bringing reputational benefits. But such initiatives reduce tourists' intentions to visit, presenting potential business risks. Our results further suggest that community support in the form of providing free accommodation to medical professionals has little impact, as it shows no significant difference to control (no CSR initiatives).

Savings or Selection? Initial Spending Reductions in the Medicare Shared Savings Program and Considerations for Reform.

Policy Points Concerns have been raised about risk selection in the Medicare Shared Savings Program (MSSP). Specifically, turnover in accountable care organization (ACO) physicians and patient panels has led to concerns that ACOs may be earning shared-savings bonuses by selecting lower-risk patients or providers with lower-risk panels. We find no evidence that changes in ACO patient populations explain savings estimates from previous evaluations through 2015. We also find no evidence that ACOs systematically manipulated provider composition or billing to earn bonuses. The modest savings and lack of risk selection in the original MSSP design suggest opportunities to build on early progress. Recent program changes provide ACOs with more opportunity to select providers with lower-risk patients. Understanding the effect of these changes will be important for guiding future payment policy. CONTEXT: The Medicare Shared Savings Program (MSSP) establishes incentives for participating accountable care organizations (ACOs) to lower spending for their attributed fee-for-service Medicare patients. Turnover in ACO physicians and patient panels has raised concerns that ACOs may be earning shared-savings bonuses by selecting lower-risk patients or providers with lower-risk panels. METHODS: We conducted three sets of analyses of Medicare claims data. First, we estimated overall MSSP savings through 2015 using a difference-in-differences approach and methods that eliminated selection bias from ACO program exit or changes in the practices or physicians included in ACO contracts. We then checked for residual risk selection at the patient level. Second, we reestimated savings with methods that address undetected risk selection but could introduce bias from other sources. These included patient fixed effects, baseline or prospective assignment, and area-level MSSP exposure to hold patient populations constant. Third, we tested for changes in provider composition or provider billing that may have contributed to bonuses, even if they were eliminated as sources of bias in the evaluation analyses. FINDINGS: MSSP participation was associated with modest and increasing annual gross savings in the 2012-2013 entry cohorts of ACOs that reached $139 to $302 per patient by 2015. Savings in the 2014 entry cohort were small and not statistically significant. Robustness checks revealed no evidence of residual risk selection. Alternative methods to address risk selection produced results that were substantively consistent with our primary analysis but varied somewhat and were more sensitive to adjustment for patient characteristics, suggesting the introduction of bias from within-patient changes in time-varying characteristics. We found no evidence of ACO manipulation of provider composition or billing to inflate savings. Finally, larger savings for physician group ACOs were robust to consideration of differential changes in organizational structure among non-ACO providers (eg, from consolidation). CONCLUSIONS: Participation in the original MSSP program was associated with modest savings and not with favorable risk selection. These findings suggest an opportunity to build on early progress. Understanding the effect of new opportunities and incentives for risk selection in the revamped MSSP will be important for guiding future program reforms.

Evaluation of a pragmatic trial of a collaborative school-based obesity prevention intervention in a low-income urban district.

Broader adoption of effective school-based obesity prevention interventions is critical to the success of ongoing efforts to address the childhood obesity epidemic. School-level barriers to adopting evidence-based interventions may be overcome by empowering school-level leaders to select appropriate intervention components. We used a quasi-experimental pragmatic trial design to evaluate a tailored obesity prevention intervention in 9 schools in a mid-sized urban school district in upstate New York from fall 2013 to spring 2016. We analyzed repeated height and weight measurements from an existing district screening system on 5882 students from intervention and control schools matched using propensity score methods. We assessed diet and physical activity changes in intervention schools using surveys and direct observation. The intervention led to a change of -0.27 (p = 0.026, 95% Confidence Interval (CI): -0.51, -0.03) and -0.28 (p = 0.031, 95% CI: -0.54, -0.03) BMI units in spring 2014 and fall 2014, respectively. There were no significant differences between intervention and control from spring 2015 to spring 2016. Despite the lack of sustained effects on BMI, we demonstrated the potential of supporting school leaders in a low-income district to implement supportive policy and practice changes and of using an existing BMI screening system to reduce the burden of health promotion evaluation.

How to choose your study design.

Research designs are broadly divided into observational studies (i.e. cross-sectional; case-control and cohort studies) and experimental studies (randomised control trials, RCTs). Each design has a specific role, and each has both advantages and disadvantages. Moreover, while the typical RCT is a parallel group design, there are now many variants to consider. It is important that both researchers and paediatricians are aware of the role of each study design, their respective pros and cons, and the inherent risk of bias with each design. While there are numerous quantitative study designs available to researchers, the final choice is dictated by two key factors. First, by the specific research question. That is, if the question is one of 'prevalence' (disease burden) then the ideal is a cross-sectional study; if it is a question of 'harm' - a case-control study; prognosis - a cohort and therapy - a RCT. Second, by what resources are available to you. This includes budget, time, feasibility re-patient numbers and research expertise. All these factors will severely limit the choice. While paediatricians would like to see more RCTs, these require a huge amount of resources, and in many situations will be unethical (e.g. potentially harmful intervention) or impractical (e.g. rare diseases). This paper gives a brief overview of the common study types, and for those embarking on such studies you will need far more comprehensive, detailed sources of information.