Adaptive social contact rates induce complex dynamics during epidemics.

Epidemics may pose a significant dilemma for governments and individuals. The personal or public health consequences of inaction may be catastrophic; but the economic consequences of drastic response may likewise be catastrophic. In the face of these trade-offs, governments and individuals must therefore strike a balance between the economic and personal health costs of reducing social contacts and the public health costs of neglecting to do so. As risk of infection increases, potentially infectious contact between people is deliberately reduced either individually or by decree. This must be balanced against the social and economic costs of having fewer people in contact, and therefore active in the labor force or enrolled in school. Although the importance of adaptive social contact on epidemic outcomes has become increasingly recognized, the most important properties of coupled human-natural epidemic systems are still not well understood. We develop a theoretical model for adaptive, optimal control of the effective social contact rate using traditional epidemic modeling tools and a utility function with delayed information. This utility function trades off the population-wide contact rate with the expected cost and risk of increasing infections. Our analytical and computational analysis of this simple discrete-time deterministic strategic model reveals the existence of an endemic equilibrium, oscillatory dynamics around this equilibrium under some parametric conditions, and complex dynamic regimes that shift under small parameter perturbations. These results support the supposition that infectious disease dynamics under adaptive behavior change may have an indifference point, may produce oscillatory dynamics without other forcing, and constitute complex adaptive systems with associated dynamics. Implications for any epidemic in which adaptive behavior influences infectious disease dynamics include an expectation of fluctuations, for a considerable time, around a quasi-equilibrium that balances public health and economic priorities, that shows multiple peaks and surges in some scenarios, and that implies a high degree of uncertainty in mathematical projections.

Human adaptation to climate change: An introduction to the special issue.

OBJECTIVES: Despite our focus on adaptation and human responses to climate, evolutionary and biological anthropologists (EBAs) are largely absent from conversations about contemporary "climate-change adaptation," a term popular in other disciplines, the development world, and related policy decisions. EBAs are missing a big opportunity to contribute to impactful, time-sensitive applied work: we have extensive theoretical and empirical knowledge pertinent to conversations about climate-change adaptation and to helping support communities as they cope. This special issue takes a tour of EBA contributions to our understanding of climate-change adaptation, from data on past and contemporary human communities to theoretically informed predictions about how individuals and communities will respond to climate change now and in the future. First, however, we must establish what we mean by "climate change" and "adaptation," along with other terms commonly used by EBAs; review what EBAs know about adaptation and about human responses to climate change; and identify just a few topics EBAs study that are pertinent to ongoing conversations about climate-change adaptation. In this article, we do just that. CONCLUSION: From our work on energy use to our work on demography, subsistence, social networks, and the salience of climate change to local communities, EBAs have an abundance of data and theoretical insights to help inform responses to contemporary climate change. We need to better reach the climate community and general public with our contributions.

Physiologic effects of furosemide in combination with water restriction when administered at 4 and 24 hours prior to high-intensity treadmill training.

Although controversial, due to its reported effectiveness in attenuating bleeding associated with exercise-induced pulmonary hemorrhage (EIPH), furosemide is currently a permitted race day medication in most North American racing jurisdictions. The objective of this study was to assess the efficacy of furosemide in reducing the presence and severity of EIPH when administered 24 hr prior to strenuous treadmill exercise. Eight exercised Thoroughbred horses received saline or 250 mg of furosemide either 4 or 24 hr prior to high-speed treadmill exercise in a balanced 3-way cross-over design. Blood samples were collected for determination of furosemide, lactate, hemoglobin, blood gas, and electrolyte concentrations. Heart rate and pulmonary arterial pressure were measured throughout the run and endoscopic examination and bronchoalveolar lavage (BAL) performed. Horses were assigned an EIPH score and the number of red blood cells in BAL fluid determined. Although not significantly different, endoscopic EIPH scores were lower in the 4-hr versus the 24-hr and saline groups. RBC counts were not significantly different between the treatment groups. Pulmonary arterial pressures were significantly increased at higher speeds; however, there were no significant differences between dose groups when controlling for speed. A small sample size and unknown bleeding history warrant a larger-scale study.

Effects of exercise, furosemide, blood depletion, and reinfusion on body fluid compartment volumes in horses.

High pulmonary blood pressure contributes to exercise-induced pulmonary hemorrhage. The objective of this study was to use bioimpedance spectroscopy to assess body fluid compartment volumes under 3 conditions in 6 racehorses: i) Pre- and post-supramaximal treadmill exercise (control); ii) Exercise 4 hours after furosemide (0.5 mg/kg body weight, IV); iii) Exercise, removal of ~14 L of blood and subsequent reinfusion of the blood. Statistical analysis used linear mixed effects models. Body compartment volumes did not change during the control runs. Total body water (TBW) (P = 0.007, P = 0.007), extracellular fluid (ECF) (P = 0.003, P = 0.003), and intracellular fluid (ICF) volumes (P = 0.04, P = 0.04) decreased pre- and post-exercise following furosemide administration. The ICF trended to decrease (P = 0.07) after slow removal of blood. Blood reinfusion increased TBW (P = 0.02, P = 0.02) and ICF (P = 0.005, P = 0.005) pre- and post-exercise.

Effets de l'exercice, du furosémide, de la diminution sanguine et de la ré-infusion sur les volumes des liquides corporels compartimentés chez les chevaux. Une pression sanguine pulmonaire élevée contribue à des hémorragies pulmonaires induites par l'exercice. L'objectif de la présente étude était d'utiliser la spectroscopie à bio-impédance pour évaluer les volumes des liquides corporels compartimentés sous trois conditions chez six chevaux de course : i) Pré- et post-supramaximal exercice au tapis roulant (témoin); ii) Exercice 4 h après administration de furosémide (0,5 mg/kg de poids corporel, IV); iii) Exercice, retrait d'environ 14 L de sang et ré-infusion subséquente du sang. Les analyses statistiques utilisaient des modèles linéaires à effets mixtes. Les volumes des compartiments corporels n'ont pas changé durant les essais témoins. Les volumes de la quantité totale d'eau corporelle (TBW) (P = 0,007, P = 0,007), de liquide extracellulaire (ECF) (P = 0,003, P = 0,003) et liquide intracellulaire (ICF) (P = 0,04, P = 0,04) ont diminué pré- et post-exercice à la suite de l'administration de furosémide. L'ICF avait tendance à diminuer (P = 0,07) à la suite du lent retrait de sang. La ré-infusion de sang augmenta la TBW (P = 0,02, P = 0,02) et l'ICF (P = 0,005, P = 0,005) pré- et post-exercice.(Traduit par Dr Serge Messier).

Cardiopulmonary function during supramaximal exercise in hypoxia, normoxia and hyperoxia in Thoroughbred horses.

Supramaximal exercise while inspiring different O2 gases may induce different responses in cardiopulmonary function at the same relative and/or absolute exercise intensity. The purpose of this study was to compare the effects of supramaximal exercise in hypoxia, normoxia and hyperoxia on cardiopulmonary function in Thoroughbred horses. Using a crossover design, five well-trained horses were made to run up a 6% grade on a treadmill at supramaximal speeds sustainable for approximately 110 sec (approximately 115% V̇O2max) while breathing normoxic gas (NO, 21% O2) or hypoxic gas (LO, 15.3% O2) in random order. Horses also ran at the same speed, incline and run time as in NO while breathing hyperoxic gas (HONO, 28.8% O2) and as in LO while breathing normoxic gas (NOLO). Runs were on different days, and cardiopulmonary variables were analyzed with repeated-measures ANOVA and the Holm-Sidák method for pairwise comparisons. Supramaximal speeds differed significantly between NO and LO (14.0 ± 0.5 [SD] m/sec vs. 12.6 ± 0.5 m/sec), but run times to exhaustion did not (112 ± 17 sec vs. 103 ± 14 sec). The V̇O2max in NO was higher than that in LO (165 ± 11 vs. 120 ± 15 ml (min× kg)), as was the arterial oxygen tension (66 ± 5 vs. 45 ± 2 Torr). Oxygen consumption was increased in HONO and NOLO compared with the values in NO and LO, respectively. Supramaximal exercise in hypoxia induces more severe hypoxemia and decreases V̇O2max compared with normoxia at the same relative intensity. Conversely, supramaximal exercise in hyperoxia alleviates hypoxemia and increases V̇O2 compared with normoxia at the same absolute intensity.

Measuring V̇O2 in hypoxic and hyperoxic conditions using dynamic gas mixing with a flow-through indirect calorimeter.

Measurements of gas exchange while breathing gases of different O2 concentrations are useful in respiratory and exercise physiology. High bias flows required in flow-through indirect calorimetry systems for large animals like exercising horses necessitate the use of inconveniently large reservoirs of mixed gases for making such measurements and can limit the amount of equilibration time that is adequate for steady-state measurements. We obviated the need to use a pre-mixed reservoir of gas in a semi-open flow-through indirect calorimeter by dynamically mixing gases and verified the theoretical accuracy and utility of making such measurements using the mass-balance N2-dilution method. We evaluated the accuracy of the technique at different inspired oxygen fractions by measuring exercising oxygen consumption (V̇O2) at two fully aerobic submaximal exercise intensities in Thoroughbred horses. Horses exercised at 24% and 50% maximum oxygen consumption (V̇O2 max) of each horse while breathing different O2 concentrations (19.5%, 21% and 25% O2). The N2-dilution technique was used to calculate V̇O2. Repeated-measures ANOVA was used to tested for differences in V̇O2 between different inspired O2 concentrations. The specific V̇O2 of the horses trotting at 24%V̇O2max and cantering at 50%V̇O2max were not significantly different among the three different inspired oxygen fractions. These findings demonstrate that reliable measurements of V̇O2 can be obtained at various inspired oxygen fractions using dynamic gas mixing and the N2-dilution technique to calibrate semi-open-circuit gas flow systems.

Changes in heart rate and heart rate variability as a function of age in Thoroughbred horses.

We investigated changes in heart rate (HR) and HR variability as a function of age in newborn foals to old Thoroughbred horses. Experiments were performed on a total of 83 healthy and clinically normal Thoroughbred horses. Resting HR decreased with age from birth. The relationship between age and HR fit the equation Y=48.2X-0.129(R2=0.705); the relationship between age and HR for horses 0-7 years old fit the equation Y=44.1X-0.179(R2=0.882). Seven-day-old horses had the highest HR values (106 ± 10.3 beat/min). The low frequency (LF) and high frequency (HF) powers increased with age in newborn to old horses. These changes in HR and HR variability appear to result from the effects of ageing. Three- to seven-year-old race horses had the lowest HR values (32.9 ± 3.5 beat/min) and the highest LF and HF powers except for the HF powers in the oldest horses. Race training may have contributed to these changes. Horses of ages greater than 25 years old had the highest HF powers and the lowest LF/HF ratios. In individual horses, 8 of the 15 horses over 25 years old had LF/HF ratios of less than 1.0; their HR variability appears to be unique, and they may have a different autonomic balance than horses of younger age.

Hypoxic training increases maximal oxygen consumption in Thoroughbred horses well-trained in normoxia.

Hypoxic training is effective for improving athletic performance in humans. It increases maximal oxygen consumption (V̇O2max) more than normoxic training in untrained horses. However, the effects of hypoxic training on well-trained horses are unclear. We measured the effects of hypoxic training on V̇O2max of 5 well-trained horses in which V̇O2max had not increased over 3 consecutive weeks of supramaximal treadmill training in normoxia which was performed twice a week. The horses trained with hypoxia (15% inspired O2) twice a week. Cardiorespiratory valuables were analyzed with analysis of variance between before and after 3 weeks of hypoxic training. Mass-specific V̇O2max increased after 3 weeks of hypoxic training (178 ± 10 vs. 194 ± 12.3 ml O2 (STPD)/(kg × min), P<0.05) even though all-out training in normoxia had not increased V̇O2max. Absolute V̇O2max also increased after hypoxic training (86.6 ± 6.2 vs. 93.6 ± 6.6 l O2 (STPD)/min, P<0.05). Total running distance after hypoxic training increased 12% compared to that before hypoxic training; however, the difference was not significant. There were no significant differences between pre- and post-hypoxic training for end-run plasma lactate concentrations or packed cell volumes. Hypoxic training may increase V̇O2max even though it is not increased by normoxic training in well-trained horses, at least for the durations of time evaluated in this study. Training while breathing hypoxic gas may have the potential to enhance normoxic performance of Thoroughbred horses.

Indexing cardiovascular and respiratory variables: allometric scaling principles.

OBJECTIVES: To describe the allometric scaling principles underlying appropriate indexing of cardiovascular and respiratory measurements obtained in adult mammals, and to propose guidelines for indexing experimental cardiovascular and respiratory data. DATABASE USED: PubMed, using the terms 'allometry', 'allometric', 'indexing', 'cardiovascular' and 'respiratory'. CONCLUSIONS: Indexing of cardiopulmonary variables is commonly used in attempts to account for the effects of body size on measurements and to standardize them. Some cardiopulmonary variables have been indexed using various functions of body mass in a process that often ignores the underlying relationship between the variable of interest and body size, as described in the allometry literature. This can result in a failure to ideally reduce the effect of body size on measurements in a manner that highlights differences. We review how commonly measured cardiopulmonary variables are related to body mass in mammalian species according to the allometry literature, and offer suggestions on how this information can be used to appropriately index cardiopulmonary variables in a simple and informative manner.

Hypoxia and CO alter O2 extraction but not peripheral diffusing capacity during maximal aerobic exercise.

PURPOSE: To determine if and how hypoxia combined with elevated carboxyhaemoglobin fraction (F HbCO) affects peripheral diffusing capacity and O2 extraction in animals exercising at their maximal aerobic capacity ([Formula: see text]). METHODS: Six goats ran on a treadmill at speeds eliciting [Formula: see text] while breathing inspired O2 fractions (F IO2) of 0.21 or 0.12 with F HbCO 0.02 or 0.30. We measured O2 consumption and arterial and mixed-venous blood variables to assess how hypoxia and elevated F HbCO individually, and in combination, alter O2 transport and utilisation. RESULTS: Peripheral diffusing capacity did not differ among the four gas combinations (P = 0.867), whereas O2 extraction fraction increased with hypoxia [0.920 ± 0.018 (SD)] and decreased with elevated F HbCO (0.792 ± 0.038) compared to control (0.897 ± 0.032). Oxygen extraction increases with hypoxia due to the sigmoid relationship between O2 saturation (SO2) and O2 partial pressures (PO2) affecting low (hypoxia) and high (normoxia) PO2 differently. Oxygen extraction decreases with elevated F HbCO because elevated F HbCO increases haemoglobin (Hb) affinity for O2 and raises SO2, especially at very low (mixed-venous) PO2. Pulmonary gas exchange was impaired only with combined hypoxia and elevated F HbCO due to hypoxia decreasing alveolar PO2 and O2 flux coupled with elevated F HbCO increasing Hb affinity for O2 and decreasing the rate of PO2 increase for a given rise in SO2. CONCLUSION: This study quantifies the mechanisms by which O2 delivery and peripheral diffusion interact to limit [Formula: see text] when O2 delivery is reduced due to breathing hypoxic gas with elevated F HbCO.

Retrospective cohort study of a microelectronics and business machine facility.

OBJECTIVES: We examined health outcomes among 34,494 workers employed at a microelectronics and business machine facility 1969-2001. METHODS: Standardized mortality ratio (SMR) and standardized incidence ratios were used to evaluate health outcomes in the cohort and Cox regression modeling to evaluate relations between scores for occupational exposures and outcomes of a priori interest. RESULTS: Just over 17% of the cohort (5,966 people) had died through 2009. All cause, all cancer, and many cause-specific SMRs showed statistically significant deficits. In hourly males, SMRs were significantly elevated for non-Hodgkin's lymphoma and rectal cancer. Salaried males had excess testicular cancer incidence. Pleural cancer and mesothelioma excesses were observed in workers hired before 1969, but no available records substantiate use of asbestos in manufacturing processes. A positive, statistically significant relation was observed between exposure scores for tetrachloroethylene and nervous system diseases. CONCLUSIONS: Few significant exposure-outcome relations were observed, but risks from occupational exposures cannot be ruled out due to data limitations and the relative youth of the cohort.

Retrospective assessment of exposure to chemicals for a microelectronics and business machine manufacturing facility.

A retrospective exposure assessment was performed for use in a health outcomes study of a facility manufacturing circuit boards, business machines, and other equipment during the years 1969-2002. A matrix was developed identifying chemical use by department-year based on company-provided information. Use of six chemical agents (fiberglass, lead, methylene chloride, methyl chloroform, perchloroethylene, and trichloroethylene) and six chemical classes (acid-base, aromatic hydrocarbons, chlorinated hydrocarbons, other hydrocarbons, chlorofluorocarbons, and metals), and general (including unspecified) chemicals was identified. The matrix also contained an assignment for each department-year categorizing the potential for use of chemicals as negligible, intermittent/incidental, or routine. These department-based exposure matrix data were combined with work history data to provide duration of potential chemical use for workers. Negligible, intermittent/incidental or routine extent-of-chemical-use categories comprised 42.6%, 39.4%, and 17.9%, respectively, of total person-years of employment. Cumulative exposure scores were also developed, representing a relative measure of the cumulative extent of potential exposure to the six chemical agents, six chemical classes, and general (including unspecified) chemicals. Additionally, the study period was divided into manufacturing eras showing trends in chemical use, and showing that process use of trichloroethylene and methylene chloride ended in the mid-1980s and the mid-1990s, respectively. This approach may be useful in other assessments addressing a variety of chemicals, and with data constraints common to retrospective chemical exposure studies.

Quality Improvement Projects and Anesthesiology Graduate Medical Education: A Systematic Review.

Quality improvement (QI) projects are essential components of graduate medical education and healthcare organizations to improve patient outcomes. We systematically reviewed the literature on QI projects in anesthesiology graduate medical education programs to assess whether these projects are leading to publications. A literature search was conducted in July 2023, using PubMed, Embase, and the Central Register of Controlled Trials (CENTRAL) for articles describing QI initiatives originating within the United States and applicable to anesthesiology residency training programs. The following data were collected: intervention(s), sample size (number of participants or events), outcome metric(s), result(s), and conclusion(s). One hundred and fifty publications were identified, and 31 articles met the inclusion criteria. A total of 2,259 residents and 72,889 events were included in this review. Educational modalities, such as simulation, training sessions, or online curricula, were the most prevalent interventions in the included studies. Pre-intervention and post-intervention assessments were the most common outcome metrics reported. Our review of the literature demonstrates that few QI projects performed within anesthesiology training programs lead to published manuscripts. Further research should aim at increasing the impact of required QI projects within the sponsoring institution and specialty.

Publications Among Pain Medicine Fellowship-Trained American Board of Anesthesiology Diplomates.

American Board of Anesthesiology (ABA) diplomates who pursue clinical fellowship training in pain medicine may be better suited to lead scholarly projects and serve as first authors of publications in peer-reviewed journals given their additional training and clinical expertise. The primary aim of this study was to determine whether ABA certification in pain medicine is associated with a greater number of peer-reviewed publications. The secondary aim included assessments of whether pain medicine fellowship training is associated with a higher publication rate (publications per year) or publication in a larger number of peer-reviewed journals. A literature search was conducted in December 2023 using the Scopus database for publications related to anesthesiology and pain medicine in the United States between 2013 and 2023. First authors identified through the search were then individually searched within the ABA physician directory. The following data were collected: author name and identification number, year of publication, publication type (article or review), year of primary anesthesiology certification, and year of fellowship, if applicable. This study identified 9,612 publications and 6,924 unique first authors. Pain medicine fellowship training was associated with a statistically significant increase (p-value < 0.001) in the number of publications (0.546; 95% confidence interval {CI}, 0.386-0.707), publications per year (0.140; 95% CI, 0.121-0.159), and publication in a larger number of peer-reviewed journals (0.256; 95% CI, 0.182-0.330) in regression models adjusted for the number of years from certification. This query of the Scopus database and ABA physician directory indicates that pain medicine fellowship training is associated with statistically significant increases in research productivity, as defined by the number of publications, publications per year, or the number of publications in peer-reviewed journals. However, these increases in research output would not lead to a marked increase in scholarship productivity to justify pursuing a fellowship for this purpose.

Phylogenetic analysis of mammalian maximal oxygen consumption during exercise.

We compiled published values of mammalian maximum oxygen consumption during exercise ( ) and supplemented these data with new measurements of for the largest rodent (capybara), 20 species of smaller-bodied rodents, two species of weasels and one small marsupial. Many of the new data were obtained with running-wheel respirometers instead of the treadmill systems used in most previous measurements of mammalian . We used both conventional and phylogenetically informed allometric regression models to analyze of 77 'species' (including subspecies or separate populations within species) in relation to body size, phylogeny, diet and measurement method. Both body mass and allometrically mass-corrected showed highly significant phylogenetic signals (i.e. related species tended to resemble each other). The Akaike information criterion corrected for sample size was used to compare 27 candidate models predicting (all of which included body mass). In addition to mass, the two best-fitting models (cumulative Akaike weight=0.93) included dummy variables coding for three species previously shown to have high (pronghorn, horse and a bat), and incorporated a transformation of the phylogenetic branch lengths under an Ornstein-Uhlenbeck model of residual variation (thus indicating phylogenetic signal in the residuals). We found no statistical difference between wheel- and treadmill-elicited values, and diet had no predictive ability for . Averaged across all models, the allometric scaling exponent was 0.839, with 95% confidence limits of 0.795 and 0.883, which does not provide support for a scaling exponent of 0.67, 0.75 or unity.

A high-resolution human contact network for infectious disease transmission.

The most frequent infectious diseases in humans--and those with the highest potential for rapid pandemic spread--are usually transmitted via droplets during close proximity interactions (CPIs). Despite the importance of this transmission route, very little is known about the dynamic patterns of CPIs. Using wireless sensor network technology, we obtained high-resolution data of CPIs during a typical day at an American high school, permitting the reconstruction of the social network relevant for infectious disease transmission. At 94% coverage, we collected 762,868 CPIs at a maximal distance of 3 m among 788 individuals. The data revealed a high-density network with typical small-world properties and a relatively homogeneous distribution of both interaction time and interaction partners among subjects. Computer simulations of the spread of an influenza-like disease on the weighted contact graph are in good agreement with absentee data during the most recent influenza season. Analysis of targeted immunization strategies suggested that contact network data are required to design strategies that are significantly more effective than random immunization. Immunization strategies based on contact network data were most effective at high vaccination coverage.

Lifelong learning and self-assessment is relevant to emergency physicians.

BACKGROUND: The Lifelong Learning and Self-assessment (LLSA) component of the American Board of Emergency Medicine (ABEM) Maintenance of Certification (MOC) program is a self-assessment exercise for physicians. Beginning in 2011, an optional continuing medical education (CME) activity was added. OBJECTIVES: As a part of a CME activity option for the LLSA, a survey was used to determine the relevancy of the LLSA readings and the degree to which medical knowledge garnered by the LLSA activity would modify clinical care. METHODS: Survey results from the 2011 LLSA CME activity were reviewed. This survey was composed of seven items, including questions about the relevancy of the readings and the impact on the physician's clinical practice. The questions used a 5-point Likert scale and data underwent descriptive analyses. RESULTS: There were 2841 physicians who took the LLSA test during the study period, of whom 1354 (47.7%) opted to participate in the 2011 LLSA CME activity. All participants completed surveys. The LLSA readings were reported to be relevant to the overall clinical practice of Emergency Medicine (69.6% strongly relevant, 28.1% some relevance, and 2.3% little or no relevance), and provided information that would likely help them change their clinical practices (high likelihood 38.8%, some likelihood 53.0%, little or no change 8.2%). CONCLUSIONS: The LLSA component of the ABEM MOC program is relevant to the clinical practice of Emergency Medicine. Through this program, physicians gain new knowledge about the practice of Emergency Medicine, some of which is reported to change physicians' clinical practices.

CIITA enhances HIV-1 attachment to CD4+ T cells leading to enhanced infection and cell depletion.

Activated CD4(+) T cells are more susceptible to HIV infection than resting T cells; the reason for this remains unresolved. Induction of CIITA and subsequent expression of the MHC class II isotype HLA-DR are hallmarks of CD4(+) T cell activation; therefore, we investigated the role of CIITA expression in T cells during HIV infection. CIITA-expressing SupT1 cells display enhanced virion attachment in a gp160/CD4-dependent manner, which results in increased HIV infection, virus release, and T cell depletion. Although increased attachment and infection of T cells correlated with HLA-DR surface expression, Ab blocking, transient expression of HLA-DR without CIITA, and short hairpin RNA knockdown demonstrate that HLA-DR does not directly enhance susceptibility of CIITA-expressing cells to HIV infection. Further analysis of the remaining MHC class II isotypes, HLA-DP and HLA-DQ, MHC class I isotypes, HLA-A, HLA-B, and HLA-C, and the class II Ag presentation genes, invariant chain and HLA-DM, demonstrate that these proteins likely do not contribute to CIITA enhancement of HIV infection. Finally, we demonstrate that in activated primary CD4(+) T cells as HLA-DR/CIITA expression increases there is a corresponding increase in virion attachment. Overall, this work suggests that induction of CIITA expression upon CD4(+) T cell activation contributes to enhanced attachment, infection, virus release, and cell death through an undefined CIITA transcription product that may serve as a new antiviral target.

Dynamics and control of diseases in networks with community structure.

The dynamics of infectious diseases spread via direct person-to-person transmission (such as influenza, smallpox, HIV/AIDS, etc.) depends on the underlying host contact network. Human contact networks exhibit strong community structure. Understanding how such community structure affects epidemics may provide insights for preventing the spread of disease between communities by changing the structure of the contact network through pharmaceutical or non-pharmaceutical interventions. We use empirical and simulated networks to investigate the spread of disease in networks with community structure. We find that community structure has a major impact on disease dynamics, and we show that in networks with strong community structure, immunization interventions targeted at individuals bridging communities are more effective than those simply targeting highly connected individuals. Because the structure of relevant contact networks is generally not known, and vaccine supply is often limited, there is great need for efficient vaccination algorithms that do not require full knowledge of the network. We developed an algorithm that acts only on locally available network information and is able to quickly identify targets for successful immunization intervention. The algorithm generally outperforms existing algorithms when vaccine supply is limited, particularly in networks with strong community structure. Understanding the spread of infectious diseases and designing optimal control strategies is a major goal of public health. Social networks show marked patterns of community structure, and our results, based on empirical and simulated data, demonstrate that community structure strongly affects disease dynamics. These results have implications for the design of control strategies.