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This paper describes the formation of, and initial results for, a new FLUXNET coordination network for ecosystem-scale methane (CH₄) measurements at 60 sites globally, organized by the Global Carbon Project in partnership with other initiatives and regional flux tower networks. The objectives of the effort are presented along with an overview of the coverage of eddy covariance (EC) CH₄ flux measurements globally, initial results comparing CH₄ fluxes across the sites, and future research directions and needs. Annual estimates of net CH₄ fluxes across sites ranged from −0.2 ± 0.02 g C m−2 yr−1 for an upland forest site to 114.9 ± 13.4 g C m−2 yr−1 for an estuarine freshwater marsh, with fluxes exceeding 40 g C m−2 yr−1 at multiple sites. Average annual soil and air temperatures were found to be the strongest predictor of annual CH₄ flux across wetland sites globally. Water table position was positively correlated with annual CH₄ emissions, although only for wetland sites that were not consistently inundated throughout the year. The ratio of annual CH₄ fluxes to ecosystem respiration increased significantly with mean site temperature. Uncertainties in annual CH₄ estimates due to gap-filling and random errors were on average ±1.6 g C m−2 yr−1 at 95% confidence, with the relative error decreasing exponentially with increasing flux magnitude across sites. Through the analysis and synthesis of a growing EC CH₄ flux database, the controls on ecosystem CH₄ fluxes can be better understood, used to inform and validate Earth system models, and reconcile differences between land surface model- and atmospheric-based estimates of CH₄ emissions.

Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC is a genetically diverse, highly heterogeneous, and rapidly evolving disease that challenges our ability to individualize treatment for incomplete responders and relapsed patients. Currently, the frontline standard chemotherapy, composed of anthracyclines, alkylating agents, and taxanes, is commonly used to treat high-risk and locally advanced TNBC. Several FDA-approved drugs that target programmed cell death protein-1 (Keytruda) and programmed death ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise in improving clinical outcomes for a subset of TNBC. These inhibitors that target key genetic mutations and specific molecular signaling pathways that drive malignant tumor growth have been used as single agents and/or in combination with standard chemotherapy regimens. Here, we review the current TNBC treatment options, unmet clinical needs, and actionable drug targets, including epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERβ), phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with chemo-resistance, aggressive dissemination, and early relapse, we hope to design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic strategy to control and eradicate incurable TNBC in the future.

Wetland methane (CH 4 ) emissions ( F C H 4 ) are important in global carbon budgets and climate change assessments. Currently, F C H 4 projections rely on prescribed static temperature sensitivity that varies among biogeochemical models. Meta-analyses have proposed a consistent F C H 4 temperature dependence across spatial scales for use in models; however, site-level studies demonstrate that F C H 4 are often controlled by factors beyond temperature. Here, we evaluate the relationship between F C H 4 and temperature using observations from the FLUXNET-CH 4 database. Measurements collected across the globe show substantial seasonal hysteresis between F C H 4 and temperature, suggesting larger F C H 4 sensitivity to temperature later in the frost-free season (about 77% of site-years). Results derived from a machine-learning model and several regression models highlight the importance of representing the large spatial and temporal variability within site-years and ecosystem types. Mechanistic advancements in biogeochemical model parameterization and detailed measurements in factors modulating CH 4 production are thus needed to improve global CH 4 budget assessments. Wetland methane emissions contribute to global warming, and are oversimplified in climate models. Here the authors use eddy covariance measurements from 48 global sites to demonstrate seasonal hysteresis in methane-temperature relationships and suggest the importance of microbial processes.

Over a 15-month period at one center, 14 patients were identified who presented with community-acquired necrotizing fasciitis due to Staphylococcus aureus infection. Their median age was 46 years, and risk factors included current or past injection-drug use (six patients) and previous methicillin-resistant infections. Four patients had no serious coexisting conditions or risk factors. At one center, 14 patients were identified who presented with community-acquired necrotizing fasciitis. All these patients survived, but most required wide surgical excision and intensive care. Necrotizing fasciitis appears to be a new, virulent form of methicillin-resistant S. aureus infection. Staphylococcus aureus is a ubiquitous pathogen and one of the most common causes of severe community-associated (also referred to as community-acquired) infections of skin and soft tissue. 1 – 4 Until recently, S. aureus strains from community-associated infections were almost uniformly susceptible to penicillinase-resistant β-lactam antibiotics (i.e., methicillin and oxacillin). However, over the past few years, community-associated infections caused by methicillin-resistant S. aureus (MRSA) have become commonplace in multiple locales in the United States and worldwide 5 – 10 ; at our center, 62 percent of community-associated S. aureus infections are due to MRSA. 11 The majority of community-associated MRSA infections have been skin and . . .

Abstract Background In 2013, New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli, a type of carbapenem-resistant Enterobacteriaceae uncommon in the United States, was identified in a tertiary care hospital (hospital A) in northeastern Illinois. The outbreak was traced to a contaminated duodenoscope. Patient-sharing patterns can be described through social network analysis and ego networks, which could be used to identify hospitals most likely to accept patients from a hospital with an outbreak. Methods Using Illinois' hospital discharge data and the Illinois extensively drug-resistant organism (XDRO) registry, we constructed an ego network around hospital A. We identified which facilities NDM outbreak patients subsequently visited and whether the facilities reported NDM cases. Results Of the 31 outbreak cases entered into the XDRO registry who visited hospital A, 19 (61%) were subsequently admitted to 13 other hospitals during the following 12 months. Of the 13 hospitals, the majority (n = 9; 69%) were in our defined ego network, and 5 of those 9 hospitals consequently reported at least 1 additional NDM case. Ego network facilities were more likely to identify cases compared to a geographically defined group of facilities (9/22 vs 10/66; P = .01); only 1 reported case fell outside of the ego network. Conclusions The outbreak hospital's ego network accurately predicted which hospitals the outbreak patients would visit. Many of these hospitals reported additional NDM cases. Prior knowledge of this ego network could have efficiently focused public health resources on these high-risk facilities. Using social network analysis to construct an ego network around a hospital that experienced an outbreak of a rare carbapenem-resistant Enterobacteriaceae, we accurately predicted which hospitals outbreak patients would subsequently visit and, therefore, the hospitals that reported additional cases.

Based on archival data from an urban school district, this retrospective correlational study examined the extent to which certain types of student-school counselor contacts, based on a student-report high school exit survey, could predict high school students' postsecondary enrollment in 2- and 4-year colleges within 5 years of graduating from high school. In addition to these variables, information such as ethnicity, grade point average, and free and reduced lunch status were used to identify other trends in the data. Multiple logistic regression analysis showed that counselor contact regarding college planning and attendance and demographic information regarding free and reduced lunch status were significant predictors of postsecondary enrollment. Counselor contact regarding goal setting, concerns about grades, and needing more college information did not significantly predict postsecondary college enrollment. Findings suggest some school counselor duties can serve as sources of social capital, which can help increase student social capital.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are endemic in the Chicago region. We assessed the regional impact of a CRE control intervention targeting high-prevalence facilities; that is, long-term acute-care hospitals (LTACHs) and ventilator-capable skilled nursing facilities (vSNFs). Methods: In July 2017, an academic–public health partnership launched a regional CRE prevention bundle: (1) identifying patient CRE status by querying Illinois’ XDRO registry and periodic point-prevalence surveys reported to public health, (2) cohorting or private rooms with contact precautions for CRE patients, (3) combining hand hygiene adherence, monitoring with general infection control education, and guidance by project coordinators and public health, and (4) daily chlorhexidine gluconate (CHG) bathing. Informed by epidemiology and modeling, we targeted LTACHs and vSNFs in a 13-mile radius from the coordinating center. Illinois mandates CRE reporting to the XDRO registry, which can also be manually queried or generate automated alerts to facilitate interfacility communication. The regional intervention promoted increased automation of alerts to hospitals. The prespecified primary outcome was incident clinical CRE culture reported to the XDRO registry in Cook County by month, analyzed by segmented regression modeling. A secondary outcome was colonization prevalence measured by serial point-prevalence surveys for carbapenemase-producing organism colonization in LTACHs and vSNFs. Results: All eligible LTACHs (n = 6) and vSNFs (n = 9) participated in the intervention. One vSNF declined CHG bathing. vSNFs that implemented CHG bathing typically bathed residents 2–3 times per week instead of daily. Overall, there were significant gaps in infection control practices, especially in vSNFs. Also, 75 Illinois hospitals adopted automated alerts (56 during the intervention period). Mean CRE incidence in Cook County decreased from 59.0 cases per month during baseline to 40.6 cases per month during intervention ( P < .001). In a segmented regression model, there was an average reduction of 10.56 cases per month during the 24-month intervention period ( P = .02) (Fig. 1), and an estimated 253 incident CRE cases were averted. Mean CRE incidence also decreased among the stratum of vSNF/LTACH intervention facilities ( P = .03). However, evidence of ongoing CRE transmission, particularly in vSNFs, persisted, and CRE colonization prevalence remained high at intervention facilities (Table 1). Conclusions: A resource-intensive public health regional CRE intervention was implemented that included enhanced interfacility communication and targeted infection prevention. There was a significant decline in incident CRE clinical cases in Cook County, despite high persistent CRE colonization prevalence in intervention facilities. vSNFs, where understaffing or underresourcing were common and lengths of stay range from months to years, had a major prevalence challenge, underscoring the need for aggressive infection control improvements in these facilities. Funding: The Centers for Disease Control and Prevention (SHEPheRD Contract No. 200-2011-42037) Disclosures: M.Y.L. has received research support in the form of contributed product from OpGen and Sage Products (now part of Stryker Corporation), and has received an investigator-initiated grant from CareFusion Foundation (now part of BD).

Oncogenic K-RAS mutations are found in virtually all pancreatic cancers, making K-RAS one of the most targeted oncoproteins for drug development in cancer therapies. Despite intense research efforts over the past three decades, oncogenic K-RAS has remained largely “undruggable”. Rather than targeting an upstream component of the RAS signaling pathway (i.e., EGFR/HER2) and/or the midstream effector kinases (i.e., RAF/MEK/ERK/PI3K/mTOR), we propose an alternative strategy to control oncogenic K-RAS signal by targeting its most downstream signaling module, Seven-In-Absentia Homolog (SIAH). SIAH E3 ligase controls the signal output of oncogenic K-RAS hyperactivation that drives unchecked cell proliferation, uncontrolled tumor growth, and rapid cancer cell dissemination in human pancreatic cancer. Therefore, SIAH is an ideal therapeutic target as it is an extraordinarily conserved downstream signaling gatekeeper indispensable for proper RAS signaling. Guided by molecular insights and core principles obtained from developmental and evolutionary biology, we propose an anti-SIAH-centered anti-K-RAS strategy as a logical and alternative anticancer strategy to dampen uncontrolled K-RAS hyperactivation and halt tumor growth and metastasis in pancreatic cancer. The clinical utility of developing SIAH as both a tumor-specific and therapy-responsive biomarker, as well as a viable anti-K-RAS drug target, is logically simple and conceptually innovative. SIAH clearly constitutes a major tumor vulnerability and K-RAS signaling bottleneck in pancreatic ductal adenocarcinoma (PDAC). Given the high degree of evolutionary conservation in the K-RAS/SIAH signaling pathway, an anti-SIAH-based anti-PDAC therapy will synergize with covalent K-RAS inhibitors and direct K-RAS targeted initiatives to control and eradicate pancreatic cancer in the future.

Anaphylaxis is a life-threatening reaction with respiratory, cardiovascular, cutaneous, or gastrointestinal manifestations resulting from exposure to an offending agent, usually a food, insect sting, medication, or physical factor. It causes approximately 1,500 deaths in the United States annually. Occasionally, anaphylaxis can be confused with septic or other forms of shock, asthma, airway foreign body, panic attack, or other entities. Urinary and serum histamine levels and plasma tryptase levels drawn after onset of symptoms may assist in diagnosis. Prompt treatment of anaphylaxis is critical, with subcutaneous or intramuscular epinephrine and intravenous fluids remaining the mainstay of management. Adjunctive measures include airway protection, antihistamines, steroids, and beta agonists. Patients taking beta blockers may require additional measures. Patients should be observed for delayed or protracted anaphylaxis and instructed on how to initiate urgent treatment for future episodes.

In the past few years, notable advances have occurred in our understanding of the epidemiology and clinical importance of drug resistance among uropathogens that cause uncomplicated urinary tract infections (UTIs) or cystitis. Guidelines recommend trimethoprim-sulfamethoxazole for empirical treatment of uncomplicated UTI unless trimethoprim-sulfamethoxazole resistance in a community exceeds 10% to 20%. The rationale for this 10% to 20% cutoff appears to be related to clinical and economical considerations and to concerns about the emergence of fluoroquinolone-resistant bacteria. In patients with uncomplicated UTIs caused by uropathogens resistant to trimethoprim-sulfamethoxazole who were treated with this drug combination, clinical outcomes were clarified recently and found to be suboptimal (<60% clinical cure). Following guidelines for empirical treatment of uncomplicated UTIs is problematic. Surveillance of antimicrobial resistance among uropathogens that cause uncomplicated UTIs is performed rarely. Hospital antibiograms provide data on resistance among bacteria that cause community-associated UTIs; however, antibiograms overestimate drug resistance among uropathogens that cause UTIs and may mislead clinicians about the prevalence of local resistance. We review options for management of uncomplicated UTIs in light of these considerations.