Polycomb Repressor Complex 1 (PRC1) in ovarian cancer: a scoping literature review.

High grade serous carcinoma (HGSC) is the most common and the deadliest histologic subtype of epithelial ovarian cancer. HGSC is a therapeutic challenge, as it recurs in 80% of patients diagnosed, often as chemoresistant disease. The mechanism of this chemoresistance is not fully elucidated, but it is partly attributed to the ability of HGSC to maintain a stem-like phenotype that enables development of resistance to current therapies. Polycomb Repressor Complexes 1 and 2 (PRC1/2) have been implicated in the maintenance of the stem cell compartment through silencing tumor suppressor genes and regulating stem cells. These complexes are comprised of multiple polycomb group (PcG) proteins that play a role in normal development, and when deregulated contribute to the development of cancer [2]. Proteins included in PRC1 include B lymphoma mouse Moloney leukemia virus insertion region (BMI1), RING1, and chromobox (CBX) proteins. We aimed to review each of the protein components of PRC1 and their mechanistic relationships to promoting chemoresistant recurrences and propagation of ovarian cancer. Where possible, we reviewed therapeutic investigations of these proteins. We utilized a scoping literature review through Covidence to identify 42 articles meeting criteria for inclusion. The authors identified four relevant articles and the Yale MeSH Analysis Grid Generator was used to establish additional keywords and heading terms. A medical librarian used these terms and articles to draft an initial search strategy within each of the following databases: MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection, yielding 439 articles based on title and abstract. Abstracts were independently reviewed by the authors, identifying 77 articles for full text review, of which 35 were ultimately excluded, leaving 42 articles for full review. Our review identified the currently known mechanisms of the subunits of PRC1 that contribute to HGSC development, recurrence, and chemoresistance. By compiling a comprehensive review of available scientific knowledge, we support and direct further investigation into PRC1 that can affect meaningful advances in the treatment of HGSC.

Efficacy of Community-Delivered PEERS® for Adolescents: Increases in Social Skills and Decreases in Social Anxiety and Loneliness.

PURPOSE: PEERS® for Adolescents is an evidence-based social skills training program developed for individuals with autism spectrum disorder (ASD), which is now widely implemented by community providers in clinics and schools. However, majority of past efficacy studies on PEERS® were conducted in controlled research settings, with limited information about its effectiveness when delivered in the community. We sought to examine the effects of PEERS® on social functioning and mental health outcomes when delivered in an outpatient autism specialty clinic. METHODS: Clinical data from 45 adolescents with social challenges (age range: 11-18 years old; 31.1% female assigned at birth) were extracted for secondary analyses. Paired t-tests were performed to examine the pre- to post-intervention changes in social and mental health outcomes. Correlations between pre- and post-change scores of outcome measures were examined. RESULTS: Self-reported social skills knowledge, caregiver-reported social skills (measured by the Social Skills Improvement Systems) and the number of get-togethers hosted, increased significantly from pre- to post-intervention. Additionally, caregiver-reported anxiety and self-reported loneliness significantly decreased from pre- to post-intervention. Exploratory analyses showed that increases in caregiver-reported social skills were associated with decreases in self-reported loneliness. CONCLUSIONS: Our findings provide evidence supporting the efficacy of PEERS® for improving social knowledge and skills of adolescents with social challenges when delivered in the community. The current study also showed the potential benefit of PEERS® for improving adolescent mental health.

Validation of the Safety and Efficacy of Apixaban as Postoperative Thromboembolism Prophylaxis for Patients with Gynecologic Malignancies.

BACKGROUND: Venous thromboembolism is a preventable complication of gynecologic cancer surgery that leads to postoperative morbidity and mortality. This study compared apixaban with enoxaparin to identify whether apixaban had the same safety and efficacy for patients undergoing gynecologic cancer surgery. METHODS: The study identified patients with a gynecologic malignancy who underwent surgery and were prescribed apixaban at discharge between June 2020 and April 2023. International Classification of Diseases 10 codes were used to identify patients who had a thromboembolism within 90 days or a bleeding event within 60 days after surgery. The rates of events for patients prescribed apixaban were compared with those for a historical cohort of patients who received enoxaparin. Fisher's exact tests were used to compare categorical variables, and t tests were used to compare continuous variables. A logistic regression was performed to compare the odds of thromboembolism between the two groups. RESULTS: Baseline patient characteristics differed in terms of body mass index (BMI), race, route of surgery, and type of cancer. Of the 490 patients in the apixaban cohort, 12 (2.4%) had a thromboembolism compared with 3 (2.1%) of the 138 patients in the enoxaparin group (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI] 0.30-4.70; p > 0.999). The odds ratio was adjusted for BMI, age, and route of surgery. A bleeding event occurred for 1 (0.2%) of the 490 patients in the apixaban group and for 1 (0.7%) of the 138 patients in the enoxaparin group. CONCLUSIONS: This validation study showed that apixaban is a safe and effective method of postoperative venous thromboembolism prophylaxis. The data provide support to previous data and guideline updates recommending the use of apixaban for postoperative prophylaxis.

Targeting Tryptophan Catabolism in Ovarian Cancer to Attenuate Macrophage Infiltration and PD-L1 Expression.

High-grade serous carcinoma (HGSC) of the fallopian tube, ovary, and peritoneum is the most common type of ovarian cancer and is predicted to be immunogenic because the presence of tumor-infiltrating lymphocytes conveys a better prognosis. However, the efficacy of immunotherapies has been limited because of the immune-suppressed tumor microenvironment (TME). Tumor metabolism and immune-suppressive metabolites directly affect immune cell function through the depletion of nutrients and activation of immune-suppressive transcriptional programs. Tryptophan (TRP) catabolism is a contributor to HGSC disease progression. Two structurally distinct rate-limiting TRP catabolizing enzymes, indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2), evolved separately to catabolize TRP. IDO1/TDO2 are aberrantly expressed in carcinomas and metabolize TRP into the immune-suppressive metabolite kynurenine (KYN), which can engage the aryl hydrocarbon receptor to drive immunosuppressive transcriptional programs. To date, IDO inhibitors tested in clinical trials have had limited efficacy, but those inhibitors did not target TDO2, and we find that HGSC cell lines and clinical outcomes are more dependent on TDO2 than IDO1. To identify inflammatory HGSC cancers with poor prognosis, we stratified patient ascites samples by IL6 status, which correlates with poor prognosis. Metabolomics revealed that IL6-high patient samples had enriched KYN. TDO2 knockdown significantly inhibited HGSC growth and TRP catabolism. The orally available dual IDO1/TDO2 inhibitor, AT-0174, significantly inhibited tumor progression, reduced tumor-associated macrophages, and reduced expression of immune-suppressive proteins on immune and tumor cells. These studies demonstrate the importance of TDO2 and the therapeutic potential of AT-0174 to overcome an immune-suppressed TME. SIGNIFICANCE: Developing strategies to improve response to chemotherapy is essential to extending disease-free intervals for patients with HGSC of the fallopian tube, ovary, and peritoneum. In this article, we demonstrate that targeting TRP catabolism, particularly with dual inhibition of TDO2 and IDO1, attenuates the immune-suppressive microenvironment and, when combined with chemotherapy, extends survival compared with chemotherapy alone.

Differences in smoking behaviors and readiness to change for patients with COPD and differing categories of depressive symptoms: a descriptive cross-sectional design.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world with nearly 90% of cases caused by tobacco smoking. Nearly 40% of people with COPD are diagnosed with depression which impacts quality of life and smoking cessation. The purpose of this study was to describe factors influencing smoking behaviors and readiness to change in people with comorbid COPD and depression. METHODS: A descriptive cross-sectional design was used. A convenience sample of 222 participants self-reported and/or had a documented diagnosis of COPD. Participants completed study measures which included the PHQ-9 for depressive symptoms, assessment of smoking behaviors using The Cigarette Dependence Scale, report of readiness to change using The Smoking Stage of Change Questionnaire, The Smoking Decisional Balance Questionnaire, and The Processes of Change Questionnaire. Electronic and paper questionnaires were used. Data was stored in RedCap and analyzed using SPSS version 26. Based on variable type, descriptive and comparative analyses were conducted using ANOVA, t-test, chi-square, Pearson correlation, linear regression, and multiple linear regression to determine the relationships between smoking behaviors, COPD, and depressive symptoms. RESULTS: Only 18 participants were classified as having no depressive symptoms. Participants who smoked had high nicotine dependence and wanted to quit smoking. Overall, participants saw more cons to smoking and were engaged in the processes of change. The majority of participants were in the maintenance or contemplation stage. Cigarette dependence could decrease by 9% if depressive symptoms are treated. CONCLUSIONS: There is a need to assess COPD patients for depression and to assess COPD patients' smoking behaviors and readiness to change. Adequate treatment of depression could promote an individual to move through the stages of change from chronic contemplation to action, thus improving smoking cessation efforts for individuals with COPD. Understanding patients' smoking behaviors and readiness to change can aid in developing personalized interventions to achieve smoking cessation and improve long-term outcomes.

A spatiotemporal analysis of cattle herd movement in relation to drinking-water sources: implications for Cryptosporidium control in rural Kenya.

Given the increasing evidence that domestic contact with livestock is a risk factor for child diarrhoea in low- and middle-income countries, there have been calls for greater quantification of human-livestock contact in such countries. This study aimed to quantify seasonality in cattle proximity to domestic water sources and household compounds and develop a preliminary landscape model of faecal deposition by cattle. A total of 120 cattle in smallholder herds in the Asembo area of Siaya County, Kenya, were tracked over 1 week in April 2018 to July 2018 and November 2018 to February 2019 using GPS tracking devices. Dung deposition and behaviour were observed among 33 cattle from these herds over 185.4 hours. Mean cattle home ranges were small at 3.78 km2 and 5.85 km2 in the wet and dry seasons, respectively. There were significant differences between seasons in home range size, distance travelled from the household, and time spent tethered, but not in the time spent at domestic water sources or home range overlap with other herds. On average, 0.76 dung deposition events/hour were observed, with higher frequency in bulls. Variation in cattle proximity to household compounds and water sources did not account for seasonal variation in child diarrhoea in this population. The preliminary landscape model of faecal deposition by cattle could be further developed to inform interventions for safe separation of livestock and people, such as fencing and separate water troughs.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Among Air Passengers in China.

BACKGROUND: Modern transportation plays a key role in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and new variants. However, little is known about the exact transmission risk of the virus on airplanes. METHODS: Using the itinerary and epidemiological data of coronavirus disease 2019 (COVID-19) cases and close contacts on domestic airplanes departing from Wuhan city in China before the lockdown on 23 January 2020, we estimated the upper and lower bounds of overall transmission risk of COVID-19 among travelers. RESULTS: In total, 175 index cases were identified among 5797 passengers on 177 airplanes. The upper and lower attack rates (ARs) of a seat were 0.60% (34/5622, 95% confidence interval [CI] .43-.84%) and 0.33% (18/5400, 95% CI .21-.53%), respectively. In the upper- and lower-bound risk estimates, each index case infected 0.19 (SD 0.45) and 0.10 (SD 0.32) cases, respectively. The seats immediately adjacent to the index cases had an AR of 9.2% (95% CI 5.7-14.4%), with a relative risk 27.8 (95% CI 14.4-53.7) compared to other seats in the upper limit estimation. The middle seat had the highest AR (0.7%, 95% CI .4%-1.2%). The upper-bound AR increased from 0.7% (95% CI 0.5%-1.0%) to 1.2% (95% CI .4-3.3%) when the co-travel time increased from 2.0 hours to 3.3 hours. CONCLUSIONS: The ARs among travelers varied by seat distance from the index case and joint travel time, but the variation was not significant between the types of aircraft. The overall risk of SARS-CoV-2 transmission during domestic travel on planes was relatively low. These findings can improve our understanding of COVID-19 spread during travel and inform response efforts in the pandemic.

Mobility in China, 2020: a tale of four phases.

2020 was an unprecedented year, with rapid and drastic changes in human mobility due to the COVID-19 pandemic. To understand the variation in commuting patterns among the Chinese population across stable and unstable periods, we used nationwide mobility data from 318 million mobile phone users in China to examine the extreme fluctuations of population movements in 2020, ranging from the Lunar New Year travel season (chunyun), to the exceptional calm of COVID-19 lockdown, and then to the recovery period. We observed that cross-city movements, which increased substantially in chunyun and then dropped sharply during the lockdown, are primarily dependent on travel distance and the socio-economic development of cities. Following the Lunar New Year holiday, national mobility remained low until mid-February, and COVID-19 interventions delayed more than 72.89 million people returning to large cities. Mobility network analysis revealed clusters of highly connected cities, conforming to the social-economic division of urban agglomerations in China. While the mass migration back to large cities was delayed, smaller cities connected more densely to form new clusters. During the recovery period after travel restrictions were lifted, the netflows of over 55% city pairs reversed in direction compared to before the lockdown. These findings offer the most comprehensive picture of Chinese mobility at fine resolution across various scenarios in China and are of critical importance for decision making regarding future public-health-emergency response, transportation planning and regional economic development, among others.

Outcomes of the First Pregnancy After Fertility-Sparing Surgery for Early-Stage Cervical Cancer.

OBJECTIVE: To evaluate outcomes of the first pregnancy after fertility-sparing surgery in patients with early-stage cervical cancer. METHODS: We performed a population-based study of women aged 18-45 years with a history of stage I cervical cancer reported to the 2000-2012 California Cancer Registry. Data were linked to the OSHPD (California Office of Statewide Health Planning and Development) birth and discharge data sets. We included patients with cervical cancer who conceived at least 3 months after a fertility-sparing surgery, which included cervical conization or loop electrosurgical excision procedure. Those undergoing trachelectomy were excluded. The primary outcome was preterm birth. Secondary outcomes included growth restriction, neonatal morbidity, stillbirth, cesarean delivery, and severe maternal morbidity. We used propensity scores to match similar women from two groups in a 1:2 ratio of case group participants to control group participants: population individuals without cancer and individuals with cervical cancer (women who delivered before their cervical cancer diagnosis). Wald statistics and logistic regressions were used to evaluate outcomes. RESULTS: Of 4,087 patients with cervical cancer, 118 (2.9%) conceived after fertility-sparing surgery, and 107 met inclusion criteria and were matched to control group participants. Squamous cell carcinoma was the most common histology (63.2%), followed by adenocarcinoma (30.8%). Patients in the case group had higher odds of preterm birth before 37 weeks of gestation compared with both control groups (21.5% vs 9.3%, odds ratio [OR] 2.7, 95% CI 1.4-5.1; 21.5% vs 12.7%, OR 1.9, 95% CI 1.0-3.6), but not preterm birth before 32 weeks. Neonatal morbidity was more common among the patients in the case group relative to those in the cervical cancer control group (15.9% vs 6.9%, OR 2.5, 95% CI 1.2-5.5). There were no differences in rates of growth restriction, stillbirth, cesarean delivery, and maternal morbidity. CONCLUSION: In a population-based cohort, patients who conceived after surgery for cervical cancer had higher odds of preterm delivery compared with control groups.

Assessing the Effect of Global Travel and Contact Restrictions on Mitigating the COVID-19 Pandemic.

Travel restrictions and physical distancing have been implemented across the world to mitigate the coronavirus disease 2019 (COVID-19) pandemic, but studies are needed to understand their effectiveness across regions and time. Based on the population mobility metrics derived from mobile phone geolocation data across 135 countries or territories during the first wave of the pandemic in 2020, we built a metapopulation epidemiological model to measure the effect of travel and contact restrictions on containing COVID-19 outbreaks across regions. We found that if these interventions had not been deployed, the cumulative number of cases could have shown a 97-fold (interquartile range 79-116) increase, as of May 31, 2020. However, their effectiveness depended upon the timing, duration, and intensity of the interventions, with variations in case severity seen across populations, regions, and seasons. Additionally, before effective vaccines are widely available and herd immunity is achieved, our results emphasize that a certain degree of physical distancing at the relaxation of the intervention stage will likely be needed to avoid rapid resurgences and subsequent lockdowns.

Incidence of myelodysplastic syndrome and acute myeloid leukemia in patients receiving poly-ADP ribose polymerase inhibitors for the treatment of solid tumors: A meta-analysis of randomized trials.

BACKGROUND: Clinical trials demonstrated that PARPi (poly [adenosine diphosphate-ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. METHODS: Medline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control. RESULTS: We identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78-2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51-19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45-1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17-5.06). CONCLUSION: The pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.

Integrated vaccination and physical distancing interventions to prevent future COVID-19 waves in Chinese cities.

The coronavirus disease 2019 (COVID-19) pandemic has posed substantial challenges to the formulation of preventive interventions, particularly since the effects of physical distancing measures and upcoming vaccines on reducing susceptible social contacts and eventually halting transmission remain unclear. Here, using anonymized mobile geolocation data in China, we devise a mobility-associated social contact index to quantify the impact of both physical distancing and vaccination measures in a unified way. Building on this index, our epidemiological model reveals that vaccination combined with physical distancing can contain resurgences without relying on stay-at-home restrictions, whereas a gradual vaccination process alone cannot achieve this. Further, for cities with medium population density, vaccination can reduce the duration of physical distancing by 36% to 78%, whereas for cities with high population density, infection numbers can be well-controlled through moderate physical distancing. These findings improve our understanding of the joint effects of vaccination and physical distancing with respect to a city's population density and social contact patterns.

Fertility preservation in women with early-stage gynecologic cancer: optimizing oncologic and reproductive outcomes.

Almost all standard therapies for gynecologic cancer, including surgical intervention, gonadotoxic chemotherapy, and radiation therapy, threaten a woman's childbearing potential. Preservation of fertility should be discussed with premenopausal women with early-stage gynecologic cancer shortly after diagnosis and, for women who desire to preserve fertility, during treatment planning. Many authors have investigated both oncologic and reproductive outcomes following fertility-sparing therapy, and there is ongoing development of assisted reproduction techniques available to cancer patients and survivors. Women with early-stage (IA1-IB1) cervical cancer may be candidates for fertility-sparing cervical conization, simple trachelectomy, or radical trachelectomy. In women with stage I epithelial ovarian cancer, fertility-sparing surgery appears safe overall, although controversy remains in patients with high-risk features (eg, high pathologic grade, clear cell histology, or stage IC disease). In women with low-grade, early-stage endometrial cancer, hormonal therapy has emerged as a viable option. Criteria for patient selection for fertility-sparing therapy are not well defined, thus patients and providers must carefully discuss potential risks and benefits. In general, in carefully selected patients, survival outcomes do not appear to differ significantly between radical and fertility-sparing approaches. Women who undergo fertility-sparing therapies may experience a number of fertility and obstetric complications. Preconception counseling with high-risk obstetric specialists is important to optimize health before a woman attempts to conceive. Identifying appropriate candidates for fertility-sparing treatments, assessing fertility potential, and helping women conceive after cancer treatment is best accomplished through multidisciplinary collaboration between gynecologic oncologists and fertility specialists.

Uncovering two phases of early intercontinental COVID-19 transmission dynamics.

BACKGROUND: The COVID-19 pandemic has posed an ongoing global crisis, but how the virus spread across the world remains poorly understood. This is of vital importance for informing current and future pandemic response strategies. METHODS: We performed two independent analyses, travel network-based epidemiological modelling and Bayesian phylogeographic inference, to investigate the intercontinental spread of COVID-19. RESULTS: Both approaches revealed two distinct phases of COVID-19 spread by the end of March 2020. In the first phase, COVID-19 largely circulated in China during mid-to-late January 2020 and was interrupted by containment measures in China. In the second and predominant phase extending from late February to mid-March, unrestricted movements between countries outside of China facilitated intercontinental spread, with Europe as a major source. Phylogenetic analyses also revealed that the dominant strains circulating in the USA were introduced from Europe. However, stringent restrictions on international travel across the world since late March have substantially reduced intercontinental transmission. CONCLUSIONS: Our analyses highlight that heterogeneities in international travel have shaped the spatiotemporal characteristics of the pandemic. Unrestricted travel caused a large number of COVID-19 exportations from Europe to other continents between late February and mid-March, which facilitated the COVID-19 pandemic. Targeted restrictions on international travel from countries with widespread community transmission, together with improved capacity in testing, genetic sequencing and contact tracing, can inform timely strategies for mitigating and containing ongoing and future waves of COVID-19 pandemic.

Effect of non-pharmaceutical interventions for containing the COVID-19 outbreak in China.

BACKGROUND: The COVID-19 outbreak containment strategies in China based on non-pharmaceutical interventions (NPIs) appear to be effective. Quantitative research is still needed however to assess the efficacy of different candidate NPIs and their timings to guide ongoing and future responses to epidemics of this emerging disease across the World. METHODS: We built a travel network-based susceptible-exposed-infectious-removed (SEIR) model to simulate the outbreak across cities in mainland China. We used epidemiological parameters estimated for the early stage of outbreak in Wuhan to parameterise the transmission before NPIs were implemented. To quantify the relative effect of various NPIs, daily changes of delay from illness onset to the first reported case in each county were used as a proxy for the improvement of case identification and isolation across the outbreak. Historical and near-real time human movement data, obtained from Baidu location-based service, were used to derive the intensity of travel restrictions and contact reductions across China. The model and outputs were validated using daily reported case numbers, with a series of sensitivity analyses conducted. RESULTS: We estimated that there were a total of 114,325 COVID-19 cases (interquartile range [IQR] 76,776 - 164,576) in mainland China as of February 29, 2020, and these were highly correlated (p<0.001, R2=0.86) with reported incidence. Without NPIs, the number of COVID-19 cases would likely have shown a 67-fold increase (IQR: 44 - 94), with the effectiveness of different interventions varying. The early detection and isolation of cases was estimated to prevent more infections than travel restrictions and contact reductions, but integrated NPIs would achieve the strongest and most rapid effect. If NPIs could have been conducted one week, two weeks, or three weeks earlier in China, cases could have been reduced by 66%, 86%, and 95%, respectively, together with significantly reducing the number of affected areas. However, if NPIs were conducted one week, two weeks, or three weeks later, the number of cases could have shown a 3-fold, 7-fold, and 18-fold increase across China, respectively. Results also suggest that the social distancing intervention should be continued for the next few months in China to prevent case numbers increasing again after travel restrictions were lifted on February 17, 2020. CONCLUSION: The NPIs deployed in China appear to be effectively containing the COVID-19 outbreak, but the efficacy of the different interventions varied, with the early case detection and contact reduction being the most effective. Moreover, deploying the NPIs early is also important to prevent further spread. Early and integrated NPI strategies should be prepared, adopted and adjusted to minimize health, social and economic impacts in affected regions around the World.

Effect of non-pharmaceutical interventions to contain COVID-19 in China.

On 11 March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic1. The strategies based on non-pharmaceutical interventions that were used to contain the outbreak in China appear to be effective2, but quantitative research is still needed to assess the efficacy of non-pharmaceutical interventions and their timings3. Here, using epidemiological data on COVID-19 and anonymized data on human movement4,5, we develop a modelling framework that uses daily travel networks to simulate different outbreak and intervention scenarios across China. We estimate that there were a total of 114,325 cases of COVID-19 (interquartile range 76,776-164,576) in mainland China as of 29 February 2020. Without non-pharmaceutical interventions, we predict that the number of cases would have been 67-fold higher (interquartile range 44-94-fold) by 29 February 2020, and we find that the effectiveness of different interventions varied. We estimate that early detection and isolation of cases prevented more infections than did travel restrictions and contact reductions, but that a combination of non-pharmaceutical interventions achieved the strongest and most rapid effect. According to our model, the lifting of travel restrictions from 17 February 2020 does not lead to an increase in cases across China if social distancing interventions can be maintained, even at a limited level of an on average 25% reduction in contact between individuals that continues until late April. These findings improve our understanding of the effects of non-pharmaceutical interventions on COVID-19, and will inform response efforts across the world.

Activity-specific mobility of adults in a rural region of western Kenya.

Improving rural household access to resources such as markets, schools and healthcare can help alleviate poverty in low-income settings. Current models of geographic accessibility to various resources rarely take individual variation into account due to a lack of appropriate data, yet understanding mobility at an individual level is key to knowing how people access their local resources. Our study used both an activity-specific survey and GPS trackers to evaluate how adults in a rural area of western Kenya accessed local resources. We calculated the travel time and time spent at six different types of resource and compared the GPS and survey data to see how well they matched. We found links between several demographic characteristics and the time spent at different resources, and that the GPS data reflected the survey data well for time spent at some types of resource, but poorly for others. We conclude that demography and activity are important drivers of mobility, and a better understanding of individual variation in mobility could be obtained through the use of GPS trackers on a wider scale.

Association of Immediate Postpartum Etonogestrel Implant Insertion and Venous Thromboembolism.

OBJECTIVE: To estimate the rate of readmissions for postpartum venous thromboembolism (VTE) during the first 30 days postdelivery between women with and without the immediate postpartum insertion of the etonogestrel contraceptive implant. METHODS: The Nationwide Readmissions Database from 2016 was used to identify women with a singleton delivery, immediate postpartum insertion of the etonogestrel contraceptive implant, and readmission for VTE within 30 days of discharge. Those with a prior history of VTE or anticoagulant therapy were excluded. These women were compared with the number of women readmitted within 30 days for VTE who did not have the contraceptive implant placed during delivery admission. RESULTS: Of 3,387,120 deliveries, 8,369 women underwent etonogestrel contraceptive implant placement during the delivery admission. There was no difference identified in the rate of readmission for VTE between exposed and unexposed women. Of these, seven had received a postpartum etonogestrel contraceptive implant (0.85/1,000; 95% CI 0.22-1.45/1,000 deliveries), compared with 1,192 without an etonogestrel contraceptive implant (0.35/1,000; 95% CI 0.33-0.37/1,000 deliveries); odds ratio (OR) 2.41; 95% CI 0.58-9.89. The rates of diabetes, thrombophilia, systemic lupus erythematosus, and cesarean birth did not differ between groups. Women who underwent etonogestrel contraceptive implant placement were younger and were more likely to have government-sponsored health insurance, a smoking history, hypertension, peripartum infection, or postpartum hemorrhage than women who did not receive an etonogestrel contraceptive implant (P<.001). After adjusting for these confounders, there remained no difference in rates of VTE, adjusted OR 1.81; 95% CI 0.44-7.45. CONCLUSION: The immediate postpartum placement of the etonogestrel contraceptive implant was not associated with an increased rate of VTE; however, our sample size was underpowered to determine no difference.

Exploring fine-scale human and livestock movement in western Kenya.

Human and livestock mobility are key factors in the transmission of several high-burden zoonoses such as rift valley fever and trypanosomiasis, yet our knowledge of this mobility is relatively poor due to difficulty in quantifying population-level movement patterns. Significant variation in the movement patterns of individual hosts means it is necessary to capture their fine-scale mobility in order to gain useful knowledge that can be extrapolated to a population level. Here we explore how the movements of people and their ruminants, and their exposure to various types of land cover, correlate with ruminant ownership and other demographic factors which could affect individual exposure to zoonoses. The study was conducted in Busia County, western Kenya, where the population are mostly subsistence farmers operating a mixed crop/livestock farming system. We used GPS trackers to collect movement data from 26 people and their ruminants for 1 week per individual in July/August 2016, and the study was repeated at the end of the same year to compare movement patterns between the short rainy and dry seasons respectively. We found that during the dry season, people and their ruminants travelled further on trips outside of the household, and that people spent less time on swampland compared to the short rainy season. Our findings also showed that ruminant owners spent longer and travelled further on trips outside the household than non-ruminant owners, and that people and ruminants from poorer households travelled further than people from relatively wealthier households. These results indicate that some individual-level mobility may be predicted by season and by household characteristics such as ruminant ownership and household wealth, which could have practical uses for assessing individual risk of exposure to some zoonoses and for future modelling studies of zoonosis transmission in similar rural areas.