Integrated Modeling, Mapping, and Simulation (IMMS) Framework for Exercise and Response Planning

EmergenCy management personnel at federal, stale, and local levels can benefit from the increased situational awareness and operational efficiency afforded by simulation and modeling for emergency preparedness, including planning, training and exercises. To support this goal, the Department of Homeland Security's Science & Technology Directorate is funding the Integrated Modeling, Mapping, and Simulation (IMMS) program to create an integrating framework that brings together diverse models for use by the emergency response community. SUMMIT, one piece of the IMMS program, is the initial software framework that connects users such as emergency planners and exercise developers with modeling resources, bridging the gap in expertise and technical skills between these two communities. SUMMIT was recently deployed to support exercise planning for National Level Exercise 2010. Threat, casualty. infrastructure, and medical surge models were combined within SUMMIT to estimate health care resource requirements for the exercise ground truth

Lapatinib-based therapy for women with advanced/metastatic HER2 positive breast cancer

Background: Lapatinib alone or in combination with other agents, mostly capecitabine is used for patients with advanced/metastatic HER2 positive breast cancer (HER2+BC) after progression on trastuzumab based therapy. Here we report our experience with lapatinib based therapy in this setting. Material and Methods: 67 consecutive patients received lapatinib based therapy. 58 (86.6%) received lapatinib + capecitabine (LC), 7 (10.4%) with other agents and 2 (3.0%) as single agent lapatinib. Data was collected from patients’ records retrospectively. Results: Objective response to lapatinib based therapy in 64 evaluable patients was 64.0% in all patients and 64.0% in patients who received LC. Median progression free survival and overall survival were 10 and 27 months in all patients and 10 and 17 months in patients who received LC, respectively. 16 (24.0%) patients had dose delay > 1 week and/or dose reduction. Conclusion: Lapatinib based therapy is an effective treatment for women with advanced/metastatic HER2+BC after prior exposure to trastuzumab. It yields meaningful response rates, progression free and overall survival. Some patients require dose adjustments. Key Words: lapatinib-based therapy, metastatic breast cancer, HER2 positive breast cancer, trastuzumab

First Cultivation and Characterization of Mycobacterium ulcerans from the Environment

Mycobacterium ulcerans infection, or Buruli ulcer, is the third most common mycobacteriosis of humans worldwide, after tuberculosis and leprosy. Buruli ulcer is a neglected, devastating, necrotizing disease, sometimes producing massive, disfiguring ulcers, with huge social impact. Buruli ulcer occurs predominantly in impoverished, humid, tropical, rural areas of Africa, where the incidence has been increasing, surpassing tuberculosis and leprosy in some regions. Besides being a disease of the poor, Buruli ulcer is a poverty-promoting chronic infectious disease. There is strong evidence that M. ulcerans is not transmitted person to person but is an environmental pathogen transmitted to humans from its aquatic niches. However, until now M. ulcerans has not been isolated in pure culture from environmental sources. This manuscript describes the first isolation, to our knowledge, of M. ulcerans in pure culture from an environmental source. This strain, which is highly virulent for mice, has microbiological features typical of African strains of M. ulcerans and was isolated from an aquatic insect from a Buruli ulcer–endemic area in Benin, West Africa. Our findings support the concept that M. ulcerans is a pathogen of humans with an aquatic environmental niche and will have positive consequences for the control of this neglected and socially important tropical disease

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Bose-Einstein correlations of charged hadrons in proton-proton collisions at s\sqrt s = 13 TeV

Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s}$ = 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s}$ = 7 TeV, as well as with theoretical predictions.[graphic not available: see fulltext]Bose-Einstein correlations of charged hadrons are measured over a broad multiplicity range, from a few particles up to about 250 reconstructed charged hadrons in proton-proton collisions at $\sqrt{s} =$ 13 TeV. The results are based on data collected using the CMS detector at the LHC during runs with a special low-pileup configuration. Three analysis techniques with different degrees of dependence on simulations are used to remove the non-Bose-Einstein background from the correlation functions. All three methods give consistent results. The measured lengths of homogeneity are studied as functions of particle multiplicity as well as average pair transverse momentum and mass. The results are compared with data from both CMS and ATLAS at $\sqrt{s} =$ 7 TeV, as well as with theoretical predictions

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Performance of missing transverse momentum reconstruction in proton-proton collisions at root s=13 TeV using the CMS detector

The performance of missing transverse momentum ((p) over right arrow (miss)(T)) reconstruction algorithms for the CMS experiment is presented, using proton-proton collisions at a center-of-mass energy of 13 TeV, collected at the CERN LHC in 2016. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The results include measurements of the scale and resolution of (p) over right arrow (miss)(T), and detailed studies of events identified with anomalous (p) over right arrow (miss)(T). The performance is presented of a (p) over right arrow (miss)(T) reconstruction algorithm that mitigates the effects of multiple proton-proton interactions, using the "pileup per particle identification" method. The performance is shown of an algorithm used to estimate the compatibility of the reconstructed (p) over right arrow (miss)(T) with the hypothesis that it originates from resolution effects.Peer reviewe

Constraints on the Higgs boson width from off-shell production and decay to Z-boson pairs

Constraints are presented on the total width of the recently discovered Higgs boson, GH, using its relative on-shell and off-shell production and decay rates to a pair of Z bosons, where one Z boson decays to an electron or muon pair, and the other to an electron, muon, or neutrino pair. The analysis is based on the data collected by the CMS experiment at the LHC in 2011 and 2012, corresponding to integrated luminosities of 5.1fb-1 at a center-of-mass energy vs=7 TeV and 19.7fb-1at vs=8 TeV. A simultaneous maximum likelihood fit to the measured kinematic distributions near the resonance peak and above the Z-boson pair production threshold leads to an upper limit on the Higgs boson width of GH<22 MeV at a 95% confidence level, which is 5.4 times the expected value in the standard model at the measured mass of mH=125.6 GeV