Leaky resistance and the conditions for the existence of lytic bacteriophage.

In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIR is maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIR in these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility-a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria-their "existence conditions."

Behaviors, movements, and transmission of droplet-mediated respiratory diseases during transcontinental airline flights.

With over 3 billion airline passengers annually, the inflight transmission of infectious diseases is an important global health concern. Over a dozen cases of inflight transmission of serious infections have been documented, and air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Despite sensational media stories and anecdotes, the risks of transmission of respiratory viruses in an airplane cabin are unknown. Movements of passengers and crew may facilitate disease transmission. On 10 transcontinental US flights, we chronicled behaviors and movements of individuals in the economy cabin on single-aisle aircraft. We simulated transmission during flight based on these data. Our results indicate there is low probability of direct transmission to passengers not seated in close proximity to an infectious passenger. This data-driven, dynamic network transmission model of droplet-mediated respiratory disease is unique. To measure the true pathogen burden, our team collected 229 environmental samples during the flights. Although eight flights were during Influenza season, all qPCR assays for 18 common respiratory viruses were negative.

The Airplane Cabin Microbiome.

Serving over three billion passengers annually, air travel serves as a conduit for infectious disease spread, including emerging infections and pandemics. Over two dozen cases of in-flight transmissions have been documented. To understand these risks, a characterization of the airplane cabin microbiome is necessary. Our study team collected 229 environmental samples on ten transcontinental US flights with subsequent 16S rRNA sequencing. We found that bacterial communities were largely derived from human skin and oral commensals, as well as environmental generalist bacteria. We identified clear signatures for air versus touch surface microbiome, but not for individual types of touch surfaces. We also found large flight-to-flight beta diversity variations with no distinguishing signatures of individual flights, rather a high between-flight diversity for all touch surfaces and particularly for air samples. There was no systematic pattern of microbial community change from pre- to post-flight. Our findings are similar to those of other recent studies of the microbiome of built environments. In summary, the airplane cabin microbiome has immense airplane to airplane variability. The vast majority of airplane-associated microbes are human commensals or non-pathogenic, and the results provide a baseline for non-crisis-level airplane microbiome conditions.

Personality and reported quality of life in Parkinson's disease.

OBJECTIVE: Personality affects an individual's ability to cope with the burden of chronic disease. However, the impact of personality on quality of life (QoL) in Parkinson's disease (PD) is not well characterized. The goal of this study is to determine the effect of personality on QoL in PD. METHODS: The study included 92 patients with idiopathic PD from Baltimore-Washington area movement disorder neurology clinics. QoL was assessed using the 37-item Parkinson's disease Quality of Life Questionnaire (PDQL) total score, and the Neuroticism-Extraversion-Openness Inventory was used to determine personality traits. RESULTS: Step-wise regression models examined the contribution of personality, depression, demographic, and PD variables on PDQL-assessed QoL. Neuroticism, conscientiousness, years of education, and depression explained 42% of the variance in the PDQL total score after adjusting for other disease variables. High neuroticism (ß = -0.727, 95% confidence interval (CI) -1.125, -0.328, p < 0.0001) and depression (ß = -9.058, 95%CI -17.46, -0.657, p = 0.035) negatively affected the PDQL, while high conscientiousness (ß = 0.468, 95%CI 0.078, 0.858, p = 0.019), and years of education (ß = 1.441, 95%CI 0.371, 2.510, p = 0.009) were positive factors. CONCLUSIONS: Personality can have a positive or negative influence on QoL in PD. PD patients with otherwise similar disease burdens and depressive symptoms may experience different levels of QoL depending on the level of neurotic or conscientious personality traits. Therefore, when interpreting patient responses on the PDQL, it is important to understand whether they reflect aspects of PD, that is, motor impairment and depression, which are amenable to treatment or whether they reflect personality traits.

Clinical Pearls in Tremor and Other Hyperkinetic Movement Disorders.

Hyperkinetic movements, such as tremor, myoclonus, chorea, and dystonia, occur in many neurologic and medical conditions. Accurate clinical evaluation is the important first step for the proper diagnosis and treatment of patients with abnormal movements.

Dynamics of shigellosis epidemics: estimating individual-level transmission and reporting rates from national epidemiologic data sets.

Shigellosis, a diarrheal disease, is endemic worldwide and is responsible for approximately 15,000 laboratory-confirmed cases in the United States every year. However, patients with shigellosis often do not seek medical care. To estimate the burden of shigellosis, we extended time-series susceptible-infected-recovered models to infer epidemiologic parameters from underreported case data. We applied the time-series susceptible-infected-recovered-based inference schemes to analyze the largest surveillance data set of Shigella sonnei in the United States from 1967 to 2007 with county-level resolution. The dynamics of shigellosis transmission show strong annual and multiyear cycles, as well as seasonality. By using the schemes, we inferred individual-level parameters of shigellosis infection, including seasonal transmissibilities and basic reproductive number (R0). In addition, this study provides quantitative estimates of the reporting rate, suggesting that the shigellosis burden in the United States may be more than 10 times the number of laboratory-confirmed cases. Although the estimated reporting rate is generally under 20%, and R0 is generally under 1.5, there is a strong negative correlation between estimates of the reporting rate and R0. Such negative correlations are likely to pose identifiability problems in underreported diseases. We discuss complementary approaches that might further disentangle the true reporting rate and R0.

Pharmacologic treatment of anxiety disorders in Parkinson disease.

OBJECTIVE: Neither best practices nor an evidence base for the pharmacologic treatment of anxiety in Parkinson disease (PD) has been established. This study investigated pharmacologic treatment of anxiety disorders in idiopathic PD and the associated clinical features. DESIGN: Cross-sectional. SETTING: Three community-based movement disorder neurology practices. PARTICIPANTS: 250 subjects with PD. MEASUREMENTS: Anxiety disorder diagnoses were established by consensus using a panel of six psychiatrists with expertise in geriatric psychiatry and movement disorders. Current medications were provided by the treating neurologists at the time of interview. RESULTS: Among subjects with anxiety disorders only, 53% were untreated with medications. When anxious subjects with comorbid depressive disorders were included, 70.8% were on medications effective for treatment of anxiety. Subjects with anxiety and comorbid depressive disorders were more likely to be treated for their psychiatric disturbances than subjects with anxiety disorders alone (odds ratio: 8.33), as were subjects with comorbid motor fluctuations (odds ratio: 3.65). There were no differences in the types of anti-anxiety medications used in regard to the presence of depression or motor fluctuations. CONCLUSIONS: These findings suggest that over half of nondepressed PD patients with clinically significant anxiety are untreated with medication. A better understanding of the role of clinical features associated with anxiety in PD, such as depression and motor fluctuations, may improve the recognition and treatment of anxiety disorders in this population.

Prevalence of psychotic symptoms in a community-based Parkinson disease sample.

OBJECTIVES: : To determine the prevalence of psychotic phenomena, including minor symptoms, in a Parkinson disease (PD) sample and compare the clinical correlates associated with the various psychotic phenomena. To evaluate the extent to which cases met National Institute of Neurological Diseases and Stroke (NINDS)/National Institute of Mental Health (NIMH)-proposed criteria for PD-associated psychosis. METHODS: : A total of 250 patients with idiopathic PD and Mini Mental State Exam scores greater than 23 from three community-based movement disorder clinics underwent comprehensive research diagnostic evaluations by a geriatric psychiatrist as part of a study on mood disorders in PD. Psychotic symptoms were categorized using a checklist, which included a breakdown of hallucinations, delusions, and minor symptoms. Clinical characteristics of groups with minor and other psychotic symptoms were compared. The NINDS/NIMH criteria for PD-psychosis were retrospectively applied. RESULTS: : Of the total sample, 26% of patients were found to have any current psychotic symptoms, with 47.7% of those having isolated minor symptoms, and 52.3% having hallucinations and/or delusions. Compared to those with no current psychiatric symptoms, minor symptoms were associated with more depressive symptoms and worse quality of life, and 90.8% of those with psychotic symptoms fulfilled the NINDS/NIMH proposed criteria. CONCLUSIONS: : Psychotic symptoms are common in PD patients, with minor psychotic phenomena present in nearly half of affected patients in a community-based sample. Psychotic symptoms, including minor phenomena, were clinically significant. The NINDS/NIMH PD-psychosis criteria captured the clinical characteristics of psychosis as it relates to PD. Longitudinal studies are needed to determine whether minor psychotic symptoms represent a precursor to hallucinations and delusions, and to further validate diagnostic criteria.

'Anxious fluctuators' a subgroup of Parkinson's disease with high anxiety and problematic on-off fluctuations.

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypical form of anxiety. To understand whether fluctuating anxiety in PD exists as part of an endophenotype that is associated with other signs or symptoms, we prospectively assessed the change in anxiety and a battery of clinical variables when transitioning from the off-dopamine medication state to the on state in 200 people with PD. We performed latent profile analysis with observed variables as latent profile indicators measuring the on-off-state difference in anxiety, depression, motor function, daily functioning, and the wearing off questionnaire 19 item scale (WOQ-19) in order to model unobserved (i.e., latent) profiles. A two-class model produced the best fit. The majority of participants, 69%, were categorized as having a 'typical on-off response' compared to a second profile constituting 31% of the sample who experienced a worsening in anxiety in the off state that was three times that of other participants. This profile referred to as "anxious fluctuators" had a Hamilton Anxiety Rating Scale change between the off and on medication state of 10.22(32.85) compared to 3.27 (7.62), higher depression scores, greater disability and was less likely to improve on select WOQ-19 items when in the on-state. Anxious fluctuators were more likely to be male and have a family history of anxiety disorder. Given the adverse impact of this profile we believe it may be important to distinguish patients with a typical on-off response from those with this more problematic course of fluctuations.

Prevalence of anxiety disorders and anxiety subtypes in patients with Parkinson's disease.

Anxiety disorders are common in Parkinson's disease (PD), but are not well characterized. This study determined the prevalence and clinical correlates of all DSM-IV-TR anxiety disorder diagnoses in a sample of 127 subjects with idiopathic PD who underwent comprehensive assessments administered by a psychiatrist and neurologist. A panel of six psychiatrists with expertise in geriatric psychiatry and/or movement disorders established by consensus all psychiatric diagnoses. Current and lifetime prevalence of at least one anxiety disorder diagnosis was 43% (n = 55) and 49% (n = 63), respectively. Anxiety disorder not otherwise specified, a DSM diagnosis used for anxiety disturbances not meeting criteria for defined subtypes, was the most common diagnosis (30% lifetime prevalence, n = 38). Compared with nonanxious subjects, panic disorder (n = 13) was associated with earlier age of PD onset [50.3 (12.2) vs. 61.0 (13.7) years, P < 0.01], higher rates of motor fluctuations [77% (10/13) vs. 39% (25/64), P = 0.01] and morning dystonia [38% (5/13) vs. 13% (8/62), P < 0.03]. This high prevalence of anxiety disorders, including disturbances often not meeting conventional diagnostic criteria, suggests that anxiety in PD is likely underdiagnosed and undertreated and refined characterization of anxiety disorders in PD is needed. In addition, certain anxiety subtypes may be clinically useful markers associated with disease impact in PD.

Dynamics of indirectly transmitted infectious diseases with immunological threshold.

There are numerous examples of human pathogens which persist in environmental reservoirs while infectious outbreaks remain rare. In this manuscript, we consider the dynamics of infectious diseases for which the primary mode of transmission is indirect and mediated by contact with a contaminated reservoir. We evaluate the realistic scenario in which the number of ingested pathogens must be above a critical threshold to cause infection in susceptible individuals. This minimal infectious dose is a consequence of the clearance effect of the innate immune system. Infected individuals shed pathogens back into the aquatic reservoir, indirectly increasing the transmittability of the pathogen to the susceptible. Building upon prior works in the study of cholera dynamics, we introduce and analyze a family of reservoir mediated SIR models with a threshold pathogen density for infection. Analyzing this family of models, we show that an outbreak can result from noninfinitesimal introductions of either infected individuals or additional pathogens in the reservoir. We devise two new measures of how likely it is that an environmentally persistent pathogen will cause an outbreak: (i) the minimum fraction of infected individuals; and (ii) the minimum fluctuation size of in-reservoir pathogens. We find an additional control parameter involving the shedding rate of infected individuals, which we term the pathogen enhancement ratio, which determines whether outbreaks lead to epidemics or endemic disease states. Thus, the ultimate outcome of disease is controlled by the strength of fluctuations and the global stability of a nonlinear dynamical system, as opposed to conventional analysis in which disease reflects the linear destabilization of a disease free equilibrium. Our model predicts that in the case of waterborne diseases, suppressing the pathogen density in aquatic reservoirs may be more effective than minimizing the number of infected individuals.

"Pseudo-syndromes" associated with Parkinson disease, dementia, apathy, anxiety, and depression.

PURPOSE OF REVIEW: Physicians treating patients with Parkinson disease must evaluate not only motor symptoms but also acquire expertise in assessing the complex behavioral features that often accompany the disease, such as dementia, apathy, anxiety, and depression. RECENT FINDINGS: There is a risk of diagnostic confusion and error because many of the behavioral and motor symptoms accentuate, overlap, or mimic each other. SUMMARY: Awareness of potential diagnostic pitfalls and "pseudo-syndromes" should lead to more accurate clinical assessment and better care for our patients.

Ambiguous absence, ambiguous presence: a qualitative study of military reserve families in wartime.

The "Global War on Terrorism" has resulted in reservists being deployed at an ever-increasing rate. However, because reservists and their families are unaccustomed to deployments, many families may experience boundary ambiguity, a state in which family members are uncertain in their perception about who is in or out of the family and who is performing which roles and tasks within the family. This qualitative description study examined boundary ambiguity in military reserve families over time. A sample of 34 reservists, spouses, and parents was interviewed 7 times within the 1st year of the reservists' return from Iraq. During deployment, all family members experienced boundary ambiguity. Gathering information and attending a family support group provided some relief for families. After the reservists returned, couples as well as those who had experienced additional life events or losses experienced the highest levels of boundary ambiguity. However, this boundary ambiguity dissipated over time, as families tended to restabilize once the reservists had returned to work and a routine had been established.

Pharmacodynamic considerations of collateral sensitivity in design of antibiotic treatment regimen.

INTRODUCTION: Antibiotics have greatly reduced the morbidity and mortality due to infectious diseases. Although antibiotic resistance is not a new problem, its breadth now constitutes a significant threat to human health. One strategy to help combat resistance is to find novel ways to use existing drugs, even those that display high rates of resistance. For the pathogens Escherichia coli and Pseudomonas aeruginosa, pairs of antibiotics have been identified for which evolution of resistance to drug A increases sensitivity to drug B and vice versa. These research groups have proposed cycling such pairs to treat infections, and similar treatment strategies are being investigated for various cancer forms as well. While an exciting treatment prospect, no cycling experiments have yet been performed with consideration of pharmacokinetics and pharmacodynamics. To test the plausibility of such schemes and optimize them, we create a mathematical model with explicit pharmacokinetic/pharmacodynamic considerations. MATERIALS AND METHODS: We evaluate antibiotic cycling protocols using pairs of such antibiotics and investigate the speed of ascent of multiply resistant mutants. RESULTS: Our analyses show that when using low concentrations of antibiotics, treatment failure will always occur due to the rapid ascent and fixation of resistant mutants. However, moderate to high concentrations of some combinations of bacteriostatic and bactericidal antibiotics with multiday cycling prevent resistance from developing and increase the likelihood of treatment success. CONCLUSION: Our results call for guarded optimism in application and development of such treatment protocols.

Controlling viral outbreaks: Quantitative strategies.

Preparing for and responding to outbreaks of serious livestock infectious diseases are critical measures to safeguard animal health, public health, and food supply. Almost all of the current control strategies are empirical, and mass culling or "stamping out" is frequently the principal strategy for controlling epidemics. However, there are ethical, ecological, and economic reasons to consider less drastic control strategies. Here we use modeling to quantitatively study the efficacy of different control measures for viral outbreaks, where the infectiousness, transmissibility and death rate of animals commonly depends on their viral load. We develop a broad theoretical framework for exploring and understanding this heterogeneity. The model includes both direct transmission from infectious animals and indirect transmission from an environmental reservoir. We then incorporate a large variety of control measures, including vaccination, antivirals, isolation, environmental disinfection, and several forms of culling, which may result in fewer culled animals. We provide explicit formulae for the basic reproduction number, R0, for each intervention and for combinations. We evaluate the control methods for a realistic simulated outbreak of low pathogenic avian influenza on a mid-sized turkey farm. In this simulated outbreak, culling results in more total dead birds and dramatically more when culling all of the infected birds.

A Numbers Game: Ribosome Densities, Bacterial Growth, and Antibiotic-Mediated Stasis and Death.

We postulate that the inhibition of growth and low rates of mortality of bacteria exposed to ribosome-binding antibiotics deemed bacteriostatic can be attributed almost uniquely to these drugs reducing the number of ribosomes contributing to protein synthesis, i.e., the number of effective ribosomes. We tested this hypothesis with Escherichia coli K-12 MG1655 and constructs that had been deleted for 1 to 6 of the 7 rRNA (rrn) operons. In the absence of antibiotics, constructs with fewer rrn operons have lower maximum growth rates and longer lag phases than those with more ribosomal operons. In the presence of the ribosome-binding "bacteriostatic" antibiotics tetracycline, chloramphenicol, and azithromycin, E. coli strains with 1 and 2 rrn operons are killed at a substantially higher rate than those with more rrn operons. This increase in the susceptibility of E. coli with fewer rrn operons to killing by ribosome-targeting bacteriostatic antibiotics is not reflected in their greater sensitivity to killing by the bactericidal antibiotic ciprofloxacin, which does not target ribosomes, but also to killing by gentamicin, which does. Finally, when such strains are exposed to these ribosome-targeting bacteriostatic antibiotics, the time before these bacteria start to grow again when the drugs are removed, referred to as the post-antibiotic effect (PAE), is markedly greater for constructs with fewer rrn operons than for those with more rrn operons. We interpret the results of these other experiments reported here as support for the hypothesis that the reduction in the effective number of ribosomes due to binding to these structures provides a sufficient explanation for the action of bacteriostatic antibiotics that target these structures. IMPORTANCE: Chemotherapeutic agents, including antibiotics, have been used for more than a century; nevertheless, there are still major gaps in our understanding of how these drugs operate which limit future advances in antibacterial chemotherapy. Although the molecular mechanisms by which antibiotics bind to their target structures are largely known, fundamental questions about how these drugs actually kill and/or inhibit the replication of bacteria remain unanswered and subjects of controversy. We postulate that for the broad class of ribosome-binding bacteriostatic antibiotics, their reducing the number of active (functional) ribosomes per cell provides a sufficient explanation for the abatement of replication and the low rate of decline in densities of viable cells of bacteria exposed to these drugs. Using E. coli K-12 constructs with deletions of from one to six of the seven ribosome-RNA operons and the ribosome-binding bacteriostatic antibiotics tetracycline, chloramphenicol, and azithromycin, we tested this hypothesis. The results of our experiments are consistent with this "numbers game" hypothesis.

Job attitudes, job satisfaction, and job affect: A century of continuity and of change.

Over the past 100 years, research on job attitudes has improved in the sophistication of methods and in the productive use of theory as a basis for fundamental research into questions of work psychology. Early research incorporated a diversity of methods for measuring potential predictors and outcomes of job attitudes. Over time, methods for statistically assessing these relationships became more rigorous, but the field also became narrower. In recent years, developments in theory and methodology have reinvigorated research, which now addresses a rich panoply of topics related to the daily flow of affect, the complexity of personal motives and dispositions, and the complex interplay of attitude objects and motivation in shaping behavior. Despite these apparent changes, a review of the concepts and substantive arguments that underpin this literature have remained remarkably consistent. We conclude by discussing how we expect that these major themes will be addressed in the future, emphasizing topics that have proven to be enduring guides for understanding the ways that people construe and react to their appraisals of their work. (PsycINFO Database Record

Episodic processes in emotional labor: perceptions of affective delivery and regulation strategies.

This study examined emotional labor processes from a within-person, episodic framework. The authors hypothesized that the influence of negative emotions on affective delivery would be lessened by regulation strategies for supervisor perceptions but not self-perceptions. In addition, difficulty maintaining display rules was hypothesized to mediate the relation between negative emotions and self-perceptions of affective delivery. Finally, the influence of surface acting strategies on these processes as well as correlations with individual differences was investigated. Hypotheses were tested using ecological momentary assessment of a sample of cheerleading instructors. Results suggest that surface actors can regulate emotions effectively on an episode-to-episode basis but find the episode more difficult. In addition, surface actors exhibit more general tendencies to devalue themselves and experience fewer positive emotions.

On the 2-Row Rule for Infectious Disease Transmission on Aircraft.

BACKGROUND: With over two billion airline passengers annually, in-flight transmission of infectious diseases is an important global health concern. Many instances of in-flight transmission have been documented, but the relative influence of the many factors (see below) affecting in-flight transmission has not been quantified. Long-standing guidance by public health agencies is that the primary transmission risk associated with air travel for most respiratory infectious diseases is associated with sitting within two rows of an infectious passenger. The effect of proximity may be one of these factors. OBJECTIVE: The aim of this study was to determine the risk of infection within and beyond the 2-row rule given by public health guidance. METHODS: We searched the literature for reports of in-flight transmission of infection which included seat maps indicating where the infectious and infected passengers were seated. FINDINGS: There is a ∼ 6% risk to passengers seated within the 2-rows of infected individual(s) and there is ∼ 2% risk to passengers seated beyond 2-rows from the infectious individual. DISCUSSION: Contact tracing limited to passengers within 2-rows of the infectious individual(s) could fail to detect other cases of infections. This has important consequences for assessing the spread of infectious diseases. CONCLUSIONS: Infection at a distance from the index case indicates other factors, such as airflow, movement of passenger/crew members, fomites and contacts between passengers in the departure gate before boarding, or after deplaning, are involved.