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Abstract Background The study of circulating biomarkers and their association with disease outcomes has become progressively complex due to advances in the measurement of these biomarkers through multiplex technologies. The Least Absolute Shrinkage and Selection Operator (LASSO) is a data analysis method that may be utilized for biomarker selection in these high dimensional data. However, it is unclear which LASSO-type method is preferable when considering data scenarios that may be present in serum biomarker research, such as high correlation between biomarkers, weak associations with the outcome, and sparse number of true signals. The goal of this study was to compare the LASSO to five LASSO-type methods given these scenarios. Methods A simulation study was performed to compare the LASSO, Adaptive LASSO, Elastic Net, Iterated LASSO, Bootstrap-Enhanced LASSO, and Weighted Fusion for the binary logistic regression model. The simulation study was designed to reflect the data structure of the population-based Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD), specifically the sample size (N = 1000 for total population, 500 for sub-analyses), correlation of biomarkers (0.20, 0.50, 0.80), prevalence of overweight (40%) and obese (12%) outcomes, and the association of outcomes with standardized serum biomarker concentrations (log-odds ratio = 0.05–1.75). Each LASSO-type method was then applied to the TESAOD data of 306 overweight, 66 obese, and 463 normal-weight subjects with a panel of 86 serum biomarkers. Results Based on the simulation study, no method had an overall superior performance. The Weighted Fusion correctly identified more true signals, but incorrectly included more noise variables. The LASSO and Elastic Net correctly identified many true signals and excluded more noise variables. In the application study, biomarkers of overweight and obesity selected by all methods were Adiponectin, Apolipoprotein H, Calcitonin, CD14, Complement 3, C-reactive protein, Ferritin, Growth Hormone, Immunoglobulin M, Interleukin-18, Leptin, Monocyte Chemotactic Protein-1, Myoglobin, Sex Hormone Binding Globulin, Surfactant Protein D, and YKL-40. Conclusions For the data scenarios examined, choice of optimal LASSO-type method was data structure dependent and should be guided by the research objective. The LASSO-type methods identified biomarkers that have known associations with obesity and obesity related conditions.

Selecting indicators and outcome measures is an essential step in program evaluation. Given the distinctiveness and specificity of many community-based programs, nonprofit managers, evaluators, and research teams rarely share the design, development, and decision-making process that transforms good ideas into a cohesive evaluation plan. However, for some national non-profit organizations that serve vulnerable target populations, such as military service members recently returned from Iraq and Afghanistan, outcomes based accountability and program effectiveness are mission-centric. This paper aims to describe the background, framework, and lessons learned from a multi-year, national program evaluation of The Mission Continues’ Fellowship Program. For this summative evaluation, standardized measures were used to assess the biopsychosocial outcomes of participating in this veteran-focused civic service and leadership program with post-9/11/01 veterans. Consistent use of rigorous program evaluation methods and standardized measures supports the optimization and dissemination of best practices and evidence-based programs for the military and veteran populations.

Asocierea hepatitelor cronice cu diverse tipuri de dislipidemii este o realitate nu numai pentru pacientul obez, la care ne aşteptăm să găsim hipercolesterolemii sau/şi hipertrigliceridemii, dar şi pentru copilul normoponderal. Cauzele acestei asocieri sunt multiple, însă trebuie să avem în vedere, în primul rând, predispoziţia familială şi transmiterea genetică a unor forme de dislipidemii. În acelaşi timp, unele dislipidemii sunt secundare hepatopatiilor cronice, astfel că se formează un cerc vicios în care tratamentul de primă intenţie a dezechilibrelor metabolice este de mare importanţă în succesul terapiei antivirale.

Chronic hepatitis association with various types of dyslipidemia is a reality not only for the obese pediatric patient, in which we expect to find hypercholesterolemia and / or hypertriglyceridemias, but also for normal weight children with hepatitis. The causes of this association are multiple, but we need to consider first the innate predisposition and transmission of genetic forms of dyslipidemia. Meanwhile, some secondary dyslipidemia are chronic liver disease related. Those considerations are forming a vicious circle in which primary treatment of metabolic imbalances has a great importance for the success of antiviral therapy.

Objective: To examine social connection as a protective factor against exam stress. Participants: 55 undergraduate students at two universities. Methods: Students were evaluated on an exam day for their hardest class and at baseline, a day in a week where they had no exams. Social connection, salivary cortisol, perceived stress, and cognitive control (measured with the Stroop test) were assessed. Exam scores were later reported. Results: Higher social connection was associated with lower perceived stress on exam day. At a small liberal arts school, higher levels of social connection were associated with higher Stroop scores. This correlation with cognitive control was not significant at a large public university. Conclusions: These findings indicate that social connection may be a protective factor in mitigating perceived stress and cognitive control capabilities may help facilitate reduced exam stress in some school environments.

Colistin is an important last-line antibiotic to treat highly resistant Enterobacter infections. Resistance to colistin has emerged among clinical isolates but has been associated with a significant growth defect. Here, we describe a clinical Enterobacter isolate with a deletion of mgrB, a regulator of colistin resistance, leading to high-level resistance in the absence of a growth defect. The identification of a path to resistance unrestrained by growth defects suggests colistin resistance could become more common in Enterobacter.

New York uses a two-tier assay to screen newborns for Krabbe disease and Pompe disease. Individual enzyme activities are measured in the first-tier, and specimens from newborns with low activity are reflexed to second tier Sanger sequencing of the associated gene. Using only this two-tiered approach, the screen positive and false positive rates were high. In this study, we added an additional step that examines the activity of four additional lysosomal enzymes. Results for all enzymes are integrated using the multivariate pattern recognition software called Collaborative Laboratory Integrated Reports (CLIR) to assess the risk for disease. Results after one year of screening using the new algorithm are compared to the prior year of screening without consideration of the additional enzymes and use of CLIR. With CLIR the number of babies referred for Krabbe disease was reduced by almost 80% (from 48 to 10) and the number of babies referred for Pompe disease was reduced by almost 32% (22 to 15).

By binding to actin filaments, non-muscle myosin II (NMII) generates actomyosin networks that hold unique contractile properties. Their dynamic nature is essential for neuronal biology including the establishment of polarity, growth cone formation and motility, axon growth during development (and axon regeneration in the adult), radial and longitudinal axonal tension, and synapse formation and function. In this review, we discuss the current knowledge on the spatial distribution and function of the actomyosin cytoskeleton in different axonal compartments. We highlight some of the apparent contradictions and open questions in the field, including the role of NMII in the regulation of axon growth and regeneration, the possibility that NMII structural arrangement along the axon shaft may control both radial and longitudinal contractility, and the mechanism and functional purpose underlying NMII enrichment in the axon initial segment. With the advances in live cell imaging and super resolution microscopy, it is expected that in the near future the spatial distribution of NMII in the axon, and the mechanisms by which it participates in axonal biology will be further untangled.

Corneal penetration is a key rate limiting step in the bioavailability of topical ophthalmic formulations that incorporate poorly permeable drugs. Recent advances have greatly aided the ocular delivery of such drugs using colloidal drug delivery systems. Ribavirin, a poorly permeable BCS class-III drug, was incorporated in bioadhesive multiple W/O/W microemulsion (ME) to improve its corneal permeability. The drug-loaded ME was evaluated regarding its physical stability, droplet size, PDI, zeta potential, ultrastructure, viscosity, bioadhesion, in vitro release, transcorneal permeability, cytotoxicity, safety and ocular tolerance. Our ME possessed excellent physical stability, as it successfully passed several cycles of centrifugation and freeze–thaw tests. The formulation has a transparent appearance due to its tiny droplet size (10 nm). TEM confirmed ME droplet size and revealed its multilayered structure. In spite of the high aqueous solubility and the low permeability of ribavirin, this unique formulation was capable of sustaining its release for up to 24 h and improving its corneal permeability by 3-fold. The in vitro safety of our ME was proved by its high percentage cell viability, while its in vivo safety was confirmed by the absence of any sign of toxicity or irritation after either a single dose or 14 days of daily dosing. Our ME could serve as a vehicle for enhanced ocular delivery of drugs with different physicochemical properties, including those with low permeability.

Thin elastic solids are easily deformed into a myriad of three-dimensional shapes, which may contain sharp localized structures as in a crumpled candy wrapper or have smooth and diffuse features like the undulating edge of a flower. Anticipating and controlling these morphologies is crucial to a variety of applications involving textiles, synthetic skins, and inflatable structures. Here, we show that a “wrinkle-to-crumple” transition, previously observed in specific settings, is a ubiquitous response for confined sheets. This unified picture is borne out of a suite of model experiments on polymer films confined to liquid interfaces with spherical, hyperbolic, and cylindrical geometries, which are complemented by experiments on macroscopic membranes inflated with gas. We use measurements across this wide range of geometries, boundary conditions, and length scales to quantify several robust morphological features of the crumpled phase, and we build an empirical phase diagram for crumple formation that disentangles the competing effects of curvature and compression. Our results suggest that crumples are a generic microstructure that emerge at large curvatures due to a competition of elastic and substrate energies.

Cancer is a complex disease affecting millions of people worldwide, with over a hundred clinically approved drugs available. In order to improve therapy, treatment, and response, it is essential to draw better maps of the targets of cancer drugs and possible side interactors. This study presents a large-scale screening method to find associations of cancer drugs with human genes. The analysis is focused on the current collection of Food and Drug Administration (FDA)-approved drugs (which includes about one hundred chemicals). The approach integrates global gene-expression transcriptomic profiles with drug-activity profiles of a set of 60 human cell lines obtained for a collection of chemical compounds (small bioactive molecules). Using a standardized expression for each gene versus standardized activity for each drug, Pearson and Spearman correlations were calculated for all possible pairwise gene-drug combinations. These correlations were used to build a global bipartite network that includes 1007 gene-drug significant associations. The data are integrated into an open web-tool called GEDA (Gene Expression and Drug Activity) which includes a relational view of cancer drugs and genes, disclosing the putative indirect interactions found for FDA-approved drugs as well as the known targets of these drugs. The results also provide insight into the complex action of pharmaceuticals, presenting an alternative view to address predicted pleiotropic effects of the drugs.

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

Conspicuous coloration coupled with secondary defensive mechanisms is known as aposematic coloration and is used in predator avoidance and defense. Classic theory argues that aposematic signals tend to be more effective in larger organisms as they are intrinsically more easily detected by predators and are also more profitable prey items. Thus, it has been hypothesized that conspicuous coloration evolves in tandem with increased body size in aposematic prey because this likely increases the visibility and efficacy of the signal. To test this hypothesis, we used a comparative phylogenetic approach to investigate associations between body size and conspicuous coloration in two North American salamander genera: Ambystoma and Plethodon, both of which secrete noxious compounds to deter predators. Our analyses showed that increased conspicuous coloration co-evolved with increased body size in Ambystoma, yet we found the opposite relationship in the Plethodon clade. We speculate this is likely because Ambystoma are generally larger than Plethodon and exhibit gregarious mating behavior. Future studies should explore the toxicity of slimy skin secretions and how this may contribute to aposematic signaling in salamanders.

Starch synthases (SSs) are responsible for depositing the majority of glucoses in starch. Structural knowledge on these enzymes that is available from the crystal structures of rice granule bound starch synthase (GBSS) and barley SSI provides incomplete information on substrate binding and active site architecture. Here we report the crystal structures of the catalytic domains of SSIV from Arabidopsis thaliana, of GBSS from the cyanobacterium CLg1 and GBSSI from the glaucophyte Cyanophora paradoxa, with all three bound to ADP and the inhibitor acarbose. The SSIV structure illustrates in detail the modes of binding for both donor and acceptor in a plant SS. CLg1GBSS contains, in the same crystal structure, examples of molecules with and without bound acceptor, which illustrates the conformational changes induced upon acceptor binding that presumably precede catalytic activity. With structures available from several isoforms of plant and non-plant SSs, as well as the closely related bacterial glycogen synthases, we analyze, at the structural level, the common elements that define a SS, the elements that are necessary for substrate binding and singularities of the GBSS family that could underlie its processivity. While the phylogeny of the SSIII/IV/V has been recently discussed, we now further report the detailed evolutionary history of the GBSS/SSI/SSII type of SSs enlightening the origin of the GBSS enzymes used in our structural analysis.

The Administrative Data Research Facilities (ADRF) Network is a new U.S.-based effort aimed at advancing the uses of administrative data in social science research. Together with Georgetown University’s Massive Data Institute, the ADRF Network hosted its first conference in November 2017 to share approaches and build collaborative opportunities. The conference illustrated the importance of private sector data, the need for data intermediaries, and the essential process of building trust in moving forward this emerging field in the United States.

Introduction: In recent years, a wide variety of rating scales and questionnaires for movement disorders have been developed and published, making reviews on their contents, and attributes convenient for the potential users. Sleep disorders are frequently present in movement disorders, and some movement disorders are accompanied by specific sleep difficulties.Aim: The aim of this study is to perform a narrative review of the most frequently used rating scales for movement disorders with sleep problems, with special attention to those recommended by the International Parkinson and Movement Disorders Society.Methods: Online databases (PubMed, SCOPUS, Web of Science, Google Scholar), related references from papers and websites and personal files were searched for information on comprehensive or global rating scales which assessed sleep disturbances in the following movement disorders: akathisia, chorea, dystonia, essential tremor, myoclonus, multiple system atrophy, Parkinson's disease, progressive supranuclear palsy, and tics and Tourette syndrome. For each rating scale, its objective and characteristics, as well as a summary of its psychometric properties and recommendations of use are described.Results: From 22 rating scales identified for the selected movement disorders, only 5 included specific questions on sleep problems. Movement Disorders Society-Unified Parkinson's Disease Rating scale (MDS-UPDRS), Non-Motor Symptoms Scale and Questionnaire (NMSS and NMSQuest), Scales for Outcomes in Parkinson's Disease (SCOPA)-Autonomic and Progressive Supranuclear Palsy Rating Scale (PSPRS) were the only rating scales that included items for assessing sleep disturbances.Conclusions: Despite sleep problems are frequent in movement disorders, very few of the rating scales addresses these specific symptoms. This may contribute to an infra diagnosis and mistreatment of the sleep problems in patients with movement disorders.

ABSTRACT Antibiotic resistance is a growing crisis and a grave threat to human health. It is projected that antibiotic-resistant infections will lead to 10 million annual deaths worldwide by the year 2050. Among the most significant threats are carbapenem-resistant Enterobacteriaceae (CRE), including carbapenem-resistant Klebsiella pneumoniae (CRKP), which lead to mortality rates as high as 40 to 50%. Few treatment options are available to treat CRKP, and the polymyxin antibiotic colistin is often the “last-line” therapy. However, resistance to colistin is increasing. Here, we identify multidrug-resistant, carbapenemase-positive CRKP isolates that were classified as susceptible to colistin by clinical diagnostics yet harbored a minor subpopulation of phenotypically resistant cells. Within these isolates, the resistant subpopulation became predominant after growth in the presence of colistin but returned to baseline levels after subsequent culture in antibiotic-free media. This indicates that the resistance was phenotypic, rather than due to a genetic mutation, consistent with heteroresistance. Importantly, colistin therapy was unable to rescue mice infected with the heteroresistant strains. These findings demonstrate that colistin heteroresistance may cause in vivo treatment failure during K. pneumoniae infection, threatening the use of colistin as a last-line treatment for CRKP. Furthermore, these data sound the alarm for use of caution in interpreting colistin susceptibility test results, as isolates identified as susceptible may in fact resist antibiotic therapy and lead to unexplained treatment failures. IMPORTANCE This is the first report of colistin-heteroresistant K. pneumoniae in the United States. Two distinct isolates each led to colistin treatment failure in an in vivo model of infection. The data are worrisome, especially since the colistin heteroresistance was not detected by current diagnostic tests. As these isolates were carbapenem resistant, clinicians might turn to colistin as a last-line therapy for infections caused by such strains, not knowing that they in fact harbor a resistant subpopulation of cells, potentially leading to treatment failure. Our findings warn that colistin susceptibility testing results may be unreliable due to undetected heteroresistance and highlight the need for more accurate and sensitive diagnostics.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by repeated episodes of REM sleep-related vocalizations and/or complex motor behaviors. Definite diagnosis of RBD is based on history and polysomnography, both of which are less accessible due to the lack of trained specialists and high cost. While RBD may be associated with disorders like narcolepsy, focal brain lesions, and encephalitis, idiopathic RBD (iRBD) may convert to Parkinson’s disease (PD) and other synucleinopathies in more than 80% of patients and it is to date the most specific clinical prodromal marker of PD. Identification of individuals at high risk for development of PD is becoming one of the most important topics for current PD-related research as well as for future treatment trials targeting prodromal PD. Furthermore, concomitant clinical symptoms, such as subtle motor impairment, hyposmia, autonomic dysfunction, or cognitive difficulties, in subjects with iRBD may herald its phenoconversion to clinically manifest parkinsonism. The assessment of these motor and non-motor symptoms in iRBD may increase the sensitivity and specificity in identifying prodromal PD subjects. This review evaluates the diagnostic accuracy of individual rating scales and validated single items for screening of RBD and the role and accuracy of available clinical, electrophysiological, imaging, and tissue biomarkers in predicting the phenoconversion from iRBD to clinically manifest synucleinopathies.

BACKGROUND:Polymeric immunoglobulin receptor (pIgR) transport of secretory immunoglobulin A (SIgA) to mucosal surfaces is thought to promote gut integrity and immunity to Salmonella enterica serovar Typhimurium (S. Typhimurium), an invasive pathogen in mice. To elucidate potential mechanisms, we assessed intestinal barrier function and both oral and systemic S. Typhimurium virulence in pIgR knockout (KO) and wildtype (WT) mice. METHODS:In uninfected animals, we harvested jejunal segments for Ussing chamber analyses of transepithelial resistance (TER); mesenteric lymph nodes (mLN) for bacterial culture; and serum and stool for IgA. Separately, we infected mice either orally or intravenously (IV) with S. Typhimurium to compare colonization, tissue dynamics, and inflammation between KOs and WTs. RESULTS:Uninfected KOs displayed decreased TER and dramatically increased serum IgA and decreased fecal IgA vs. WT; however, KO mLNs yielded fewer bacterial counts. Remarkably, WTs challenged orally with S. Typhimurium exhibited increased splenomegaly, tissue colonization, and pro-inflammatory cytokines vs. pIgR KOs, which showed increased survival following either oral or IV infection. CONCLUSIONS:Absence of pIgR compromises gut integrity but does not exacerbate bacterial translocation nor S. Typhimurium infection. These findings raise the possibility that immune adaptation to increased gut permeability and elevated serum IgA in the setting of SIgA deficiency provides compensatory protection against invasive gut pathogens.

Breast cancer is the most common cancer in women in both developed and developing countries and the second most common cancer in the world. Developing countries are increasingly adopting a Western lifestyle, such as changes in diet and delayed first childbirth, lower parity, and shorter periods of breastfeeding, which are important determinants of a higher incidence of breast cancer among those regions. Low- and middle-income countries (LMICs) represent most of the countries with the highest mortality rates, ranging from 40% to 60%. Furthermore, developing countries account for scarce survival data, and the few data available coincide with the observed incidence and mortality differences. Five-year survival rates for breast cancer are much worse for LMICs countries such as Brazil, India, and Algeria in comparison with the United States and Sweden. Paucity of early detection programs explain these poor survival rates, which results in a high proportion of women presenting with late-stage disease, along with lack of adequate diagnosis and treatment facilities. Emphasis is urgently needed on health education, to promote early diagnosis of breast cancer, highlighting the importance of creating more public facilities that provide treatment, which are key components for the improvement in breast cancer care in developing countries.

OBJECTIVES/SPECIFIC AIMS: To describe the epidemiology of patients with carbapenem-resistant Enterobacteriaceae (CRE) bacteriuria in metropolitan Atlanta, GA and to identify risk factors associated with progression to an invasive CRE infection. We hypothesize that having an indwelling urinary catheter increases the risk of progression. METHODS/STUDY POPULATION: The Georgia Emerging Infections Program (EIP) performs active population- and laboratory-based surveillance to identify CRE isolated from a sterile site (e.g. blood) or urine among patients who reside in the 8-county metropolitan Atlanta area (population ~4 million). The Georgia EIP performs a chart review of each case to extract data on demographics, culture location, resistance patterns, healthcare exposures, and other underlying risk factors. We used a retrospective cohort study design to include all Georgia EIP cases with Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, or Klebsiella (formerly Enterobacter) aerogenes, adapting the current EIP definition of resistance to only include isolates resistant to meropenem, imipenem or doripenem (minimum inhibitory concentration ≥ 4) first identified in a urine culture from 8/1/2011 to 7/31/2017. Patients with CRE identified in a sterile site culture prior to a urine culture will be excluded. Within this cohort, we will identify which patients had a subsequent similar CRE isolate identified from a sterile site between one day and one year after the original urine culture was identified (termed “progression”). CRE isolates will be defined as similar if they are the same species and have the same carbapenem susceptibility pattern. Univariable analyses using T-tests or other nonparametric tests for continuous variables, and Chi-square tests (or Fisher’s exact tests as appropriate) for categorical variables will compare patient demographics, comorbidities and presence of invasive devices including urinary catheters between patients who had progression to an invasive infection and those who did not have progression. Covariates with a p-value of < 0.2 will be eligible for inclusion in the multivariable logistic regression model with progression to invasive infection as the primary outcome. All statistical analyses will be done in SAS 9.4. RESULTS/ANTICIPATED RESULTS: From 8/1/2011 to 7/31/2017 we have preliminarily identified 546 patients with CRE first identified in urine, representing an annual incidence rate of 1.1 cases per 100,000 population. Most cases were K. pneumoniae (352, 64%), followed by E. coli (117, 21%), E. cloacae (48, 9%), K. aerogenes (18, 3%), and K. oxytoca (11, 2%). The mean patient age was 64 +/− 18 years and the majority (308, 56%) were female. Clinical characterization through chart review was available for 507 patients. The majority of the patients were black (301, 59%), followed by white (166, 33%), Asian (12, 2%), and other or unknown race (28, 6%). 466 (92%) patients had at least one underlying comorbid condition with a median Charlson Comorbidity Index of 3 (IQR 1-5). 460 (91%) infections were considered healthcare-associated (366 community-onset and 94 hospital-onset), while 44 (9%) were community-associated. 279 (55%) patients had a urinary catheter within the two days prior to the CRE culture. The analysis of patients who progress to an invasive CRE infection, including the results of the univariable and multivariable analyses assessing risk factors for progression is in progress and will be reported in the future. DISCUSSION/SIGNIFICANCE OF IMPACT: In metropolitan Atlanta, the annual incidence of CRE first isolated in urine was estimated to be 1.1 cases per 100,000 population between 2011 and 2017, with the majority of the cases being K. pneumoniae. Most patients had prior healthcare exposure and more than 50% of the patients had a urinary catheter. Our anticipated results will identify risk factors associated with progression from CRE bacteriuria to an invasive infection with a specific focus on having a urinary catheter, as this is a potentially modifiable characteristic that could be a target of future interventions.

First paragraphs: In 1962, Ms. Fannie Lou Hamer traveled to the county seat in Indianola, Mississippi, in order to register to vote. This wasn’t her first time and it wouldn’t be the last. Although she had been warned with threats of violence and threats of death, she was determined to continue until she was able to exercise her right to participate in electoral politics. Upon her return to the Marlow Plantation, the plantation owner, W.D., confronted her. She had been a dedicated employee for 18 years as a share­cropper, time- and recordkeeper, cook, and domes­tic. He told her to withdraw her application for voter registration or leave. Her home, as paltry as it was, was a condition of her employment and that of her husband, Pap. Like many African Ameri­cans, she faced homelessness and joblessness as the price of political participation. She must have feared with good reason that she would be lynched...

Diagnostic test sensitivity affects rate estimates for laboratory-confirmed influenza–associated hospitalizations. We used data from FluSurv-NET, a national population-based surveillance system for laboratory-confirmed influenza hospitalizations, to capture diagnostic test type by patient age and influenza season. We calculated observed rates by age group and adjusted rates by test sensitivity. Test sensitivity was lowest in adults >65 years of age. For all ages, reverse transcription PCR was the most sensitive test, and use increased from 65 years. After 2009, hospitalization rates adjusted by test sensitivity were ≈15% higher for children 65 years of age. Test sensitivity adjustments improve the accuracy of hospitalization rate estimates.

One objective of the Emerging Infections Program (EIP) of the US Centers for Disease Control and Prevention is to provide training opportunities in infectious disease epidemiology. To determine the extent of training performed since the program's inception in 1995, we reviewed training efforts at the 10 EIP sites. By 2015, all sites hosted trainees (most were graduate public health students and physicians) who worked on a variety of infectious disease surveillance and epidemiologic projects. Trainee projects at all sites were used for graduate student theses or practicums. Numerous projects resulted in conference presentations and publications in peer-reviewed journals. Local public health and health care partners have also benefitted from EIP presentations and training. Consideration should be given to standardizing and documenting EIP training and to sharing useful training initiatives with other state and local health departments and academic institutions.

Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.

The acidity constants Ka1 and Ka2 of 2-(5-mercapto-1,3,4-thiadiazol-2-ylthio)acetic acid have been determined both by experimental and theoretical methods. pKa computations at B3LYP/6-311+G(d,p) level of theory were carried out for the two tautomeric forms, thiol and thione, of the above-mentioned acid. Comparisons between the experimental and theoretical values led to the establishing of the most stable tautomer of 2-(5-mercapto-1,3,4-thiadiazol-2-ylthio)acetic acid in aqueous solution. Also, a DFT study regarding the reactivity, aromaticity and population analysis of the two tautomers has been performed.