Analysing how changes in the health status of healthcare workers affects epidemic outcomes.

During a disease outbreak, healthcare workers (HCWs) are essential to treat infected individuals. However, these HCWs are themselves susceptible to contracting the disease. As more HCWs get infected, fewer are available to provide care for others, and the overall quality of care available to infected individuals declines. This depletion of HCWs may contribute to the epidemic's severity. To examine this issue, we explicitly model declining quality of care in four differential equation-based susceptible, infected and recovered-type models with vaccination. We assume that vaccination, recovery and survival rates are affected by quality of care delivered. We show that explicitly modelling HCWs and accounting for declining quality of care significantly alters model-predicted disease outcomes, specifically case counts and mortality. Models neglecting the decline of quality of care resulting from infection of HCWs may significantly under-estimate cases and mortality. These models may be useful to inform health policy that may differ for HCWs and the general population. Models accounting for declining quality of care may therefore improve the management interventions considered to mitigate the effects of a future outbreak.

Low energy secondary electron induced damage of condensed nucleotides.

Radiation damage and stimulated desorption of nucleotides 2'-deoxyadenosine 5'-monophosphate (dAMP), adenosine 5'-monophosphate (rAMP), 2'-deoxycytidine 5'-monophosphate (dCMP), and cytidine 5'-monophosphate (rCMP) deposited on Au have been measured using x-rays as both the probe and source of low energy secondary electrons. The fluence dependent behavior of the O-1s, C-1s, and N-1s photoelectron transitions was analyzed to obtain phosphate, sugar, and nucleobase damage cross sections. Although x-ray induced reactions in nucleotides involve both direct ionization and excitation, the observed bonding changes were likely dominated by the inelastic energy-loss channels associated with secondary electron capture and transient negative ion decay. Growth of the integrated peak area for the O-1s component at 531.3 eV, corresponding to cleavage of the C-O-P phosphodiester bond, yielded effective damage cross sections of about 23 Mb and 32 Mb (1 Mb = 10-18 cm2) for AMP and CMP molecules, respectively. The cross sections for sugar damage, as determined from the decay of the C-1s component at 286.4 eV and the glycosidic carbon at 289.0 eV, were slightly lower (about 20 Mb) and statistically similar for the r- and d- forms of the nucleotides. The C-1s component at 287.6 eV, corresponding to carbons in the nucleobase ring, showed a small initial increase and then decayed slowly, yielding a low damage cross section (∼5 Mb). Although there is no statistical difference between the sugar forms, changing the nucleobase from adenine to cytidine has a slight effect on the damage cross section, possibly due to differing electron capture and transfer probabilities.

Correlation between measles vaccine doses: implications for the maintenance of elimination.

Measles eradication efforts have been successful at achieving elimination in many countries worldwide. Such countries actively work to maintain this elimination by continuing to improve coverage of two routine doses of measles vaccine following measles elimination. While improving measles vaccine coverage is always beneficial, we show, using a steady-state analysis of a dynamical model, that the correlation between populations receiving the first and second routine dose also has a significant impact on the population immunity achieved by a specified combination of first and second dose coverage. If the second dose is administered to people independently of whether they had the first dose, high second-dose coverage improves the proportion of the population receiving at least one dose, and will have a large effect on population immunity. If the second dose is administered only to people who have had the first dose, high second-dose coverage reduces the rate of primary vaccine failure, but does not reach people who missed the first dose; this will therefore have a relatively small effect on population immunity. When doses are administered dependently, and assuming the first dose has higher coverage, increasing the coverage of the first dose has a larger impact on population immunity than does increasing the coverage of the second. Correlation between vaccine doses has a significant impact on the level of population immunity maintained by current vaccination coverage, potentially outweighing the effects of age structure and, in some cases, recent improvements in vaccine coverage. It is therefore important to understand the correlation between vaccine doses as such correlation may have a large impact on the effectiveness of measles vaccination strategies.

High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas.

The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100-150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders.

A quantitative study of tau pathology in 11 cases of chronic traumatic encephalopathy.

AIMS: To quantify tau pathology of chronic traumatic encephalopathy (CTE) and investigate influence of dot-like lesions (DL), brain region, comorbidity and sporting career length. METHODS: Densities of neurofibrillary tangles (NFT), astrocytic tangles (AT), DL, oligodendroglial inclusions (GI), neuropil threads (NT), vacuoles, neurons and enlarged neurons (EN) were measured in tau-immunoreactive sections of upper cortical laminae of frontal and temporal lobes, hippocampus (HC), amygdala and substantia nigra (SN) in 11 cases of CTE. RESULTS: DL were a consistent finding in CTE. Densities of NFT, NT and DL were greatest in sectors CA1 and CA2 of the HC. Densities of AT were lower than NFT, small numbers of GI were recorded in temporal lobe and low densities of vacuoles and EN were consistently present. ß-Amyloid-containing neuritic plaques (NP) also occurred at low density. Densities of NFT, NT, DL and AT were greater in sulci than gyri, while vacuole density was greater in gyri. Principal components analysis (PCA) suggested that sporting career length and densities of NFT in entorhinal cortex, NT in CA2 and SN and vacuolation in the DG were significant sources of variation among cases. CONCLUSION: DL are frequent in CTE suggesting affinity with argyrophilic grain disease (AGD) and Parkinson's disease dementia (PD-Dem). Densities of AT in all regions and NT/DL in sectors CA2/4 were consistent features of CTE. The 11 cases are neuropathologically heterogeneous which may result from genetic diversity, and variation in anatomical pathways subjected to trauma.

Optimal vaccine schedules to maintain measles elimination with a two-dose routine policy.

Measles was eliminated in the Americas in 2002 by a combination of routine immunizations and supplementary immunization activities. Recent outbreaks underscore the importance of reconsidering vaccine policy in order to maintain elimination. We constructed an age-structured dynamical model for the distribution of immunity in a population with routine immunization and without disease, and analysed the steady state for an idealized age structure and for real age structures of countries in the Americas. We compared the level of immunity maintained by current policy in these countries to the level maintainable by an optimal policy. The optimal age target for the first routine dose of measles vaccine depends on the timing and coverage of both doses. Similarly, the optimal age target for the second dose of measles vaccine depends on the timing and coverage of the first dose. The age targets for the first and second doses of measles vaccine should be adjusted for the post-elimination era, by specifically accounting for current context, including realized coverage of both doses, and altered maternal immunity. Doing so can greatly improve the proportion immune within a population, and therefore the chances of maintaining measles elimination, without changing coverage.

The Strategy of Predator Evasion in Response to a Visual Looming Stimulus in Zebrafish (Danio rerio).

A diversity of animals survive encounters with predators by escaping from a looming visual stimulus. Despite the importance of this behavior, it is generally unclear how visual cues facilitate a prey's survival from predation. Therefore, the aim of this study was to understand how the visual angle subtended on the eye of the prey by the predator affects the distance of adult zebrafish (Danio rerio) from predators. We performed experiments to measure the threshold visual angle and mathematically modeled the kinematics of predator and prey. We analyzed the responses to the artificial stimulus with a novel approach that calculated relationships between hypothetical values for a threshold-stimulus angle and the latency between stimulus and response. These relationships were verified against the kinematic responses of zebrafish to a live fish predator (Herichthys cyanoguttatus). The predictions of our model suggest that the measured threshold visual angle facilitates escape when the predator's approach is slower than approximately twice the prey's escape speed. These results demonstrate the capacity and limits to how the visual angle provides a prey with the means to escape a predator.

Una diversidad de animales sobrevive a los encuentros con los depredadores al escapar de un inminente estímulo visual. A pesar de la importancia de este comportamiento, generalmente no está claro cómo las señales visuales facilitan la supervivencia de una presa de la depredación. Por lo tanto, el objetivo del presente estudio fue comprender cómo el ángulo visual que el depredador subtiende en el ojo de la presa afecta la distancia del pez cebra adulto (Danio rerio) de los depredadores. Realizamos experimentos para medir el ángulo visual del umbral y modelamos matemáticamente la cinemática del depredador y la presa. Analizamos las respuestas al estímulo artificial con un enfoque novedoso que calculaba las relaciones entre los valores hipotéticos para un ángulo umbral-estímulo y la latencia entre el estímulo y la respuesta. Estas relaciones se verificaron contra las respuestas cinemáticas del pez cebra a un depredador de peces vivos (Herichthys cyanoguttatus). Las predicciones de nuestro modelo sugieren que el ángulo visual del umbral medido facilita el escape cuando el enfoque del depredador es más lento que aproximadamente el doble de la velocidad de escape de la presa. Estos resultados demuestran la capacidad y los límites de cómo el ángulo visual proporciona a una presa los medios para escapar de un depredador.

Bone and joint mycobacterial infection: a retrospective review of cases presenting to a UK district hospital.

PURPOSE: Peterborough has one of the highest rates of tuberculosis (TB) in the east of England. We reviewed the epidemiology, management and outcome of all cases of bone and joint TB (BJTB) diagnosed since 2000. METHODOLOGY: Retrospective review of all adult cases of BJTB between 1 January 2000 and 31 December 2015. Patients' notes were reviewed with regard to their presentation, investigation, management and outcomes. RESULTS: In total, 21 patients diagnosed with BJTB were reviewed. Thoracic and lumbar spine were the most common sites affected (62 %). The most common clinical manifestations included localized pain (76 %), fever (53 %) and weight loss (48 %). Fourteen (67 %) patients had a bone biopsy or aspirate sent for microbiological investigation; none were smear-positive, but 11 were culture-positive. Eleven patients (77 %) were fully susceptible to anti-tuberculous drugs, one was isoniazid-resistant and one was pyrazinamide-resistant. Anti-tuberculous therapy was given for 6-16 months. Nineteen (90 %) patients completed therapy. CONCLUSIONS: BJTB requires a high index of clinical suspicion. BJTB should be considered in any patient with unexplained pain, fever and weight loss. The diagnosis is proven by aspiration and biopsy and should be undertaken as soon as possible for culture purposes, as microscopy alone can be negative.

Screening for Vitamin D Deficiency in Black Americans: Comparison of Total, Free, Bioavailable 25 Hydroxy Vitamin D Levels with Parathyroid Hormone Levels and Bone Mineral Density.

OBJECTIVES: There is debate surrounding the adequacy of total and free 25 hydroxy vitamin D [25(OH)D] levels in black Americans who have inherently high bone mineral density [BMD] and low serum concentration of vitamin D binding proteins [VDBP]. DESIGN: Retrospective analysis of serum samples and BMD analyses from the African American Health Study [AAHS] cohort. SETTING: The AAHS is a population-based longitudinal study initiated to examine issues of disability and frailty among urban-dwelling black Americans in the city of Saint Louis, Missouri. PARTICIPANTS: 122 men and 206 women, age 60.2 ± 4.3 years. INTERVENTION: Retrospective analysis. MEASUREMENTS: Total 25(OH)D, VDBP, PTH, and BMD of the lumbar spine and hip by dual energy x-ray photometry (DXA). Free and bioavailable vitamin D levels were calculated using serum concentrations and affinity constants for the VDBP (Gc1F and Gc1S) phenotypes. RESULTS: Serum total 25(OH)D levels were 14.6 ± 8.9 ng/mL (36 ± 22 nmol/L). Vitamin D insufficiency was estimated by compensatory elevations of PTH above the normal range (> 65 pg/mL). PTH levels were within the normal reference range in > 95% of the samples at total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L). There was no difference in the correlation of the reciprocal relationship of vitamin D vs parathyroid hormone between the VDBP phenotypes. Receiver operating characteristic curve analyses indicated that serum total 25(OH)D discriminated sufficiency from insufficiency at least as well as the calculated levels of the free and bioavailable vitamin D. Very low levels of total 25(OH)D (≤ 8 ng/mL, ≤20 nmol/L) were associated with decreased BMD (p=0.02), but higher levels of 25(OH)D did not show statistical differences in BMD. CONCLUSION: Total 25(OH)D levels of ≤ 8ng/mL (≤20 nmol/L) are associated with clinically significant changes in BMD, whereas total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L) suppressed PTH and were not associated with deficiencies in BMD. Lower levels of 25(OH)D may be acceptable for bone health in black than in white Americans.

Insulin-responsive compartments containing GLUT4 in 3T3-L1 and CHO cells: regulation by amino acid concentrations.

In fat and muscle, insulin stimulates glucose uptake by rapidly mobilizing the GLUT4 glucose transporter from a specialized intracellular compartment to the plasma membrane. We describe a method to quantify the relative proportion of GLUT4 at the plasma membrane, using flow cytometry to measure a ratio of fluorescence intensities corresponding to the cell surface and total amounts of a tagged GLUT4 reporter in individual living cells. Using this assay, we demonstrate that both 3T3-L1 and CHO cells contain intracellular compartments from which GLUT4 is rapidly mobilized by insulin and that the initial magnitude and kinetics of redistribution to the plasma membrane are similar in these two cell types when they are cultured identically. Targeting of GLUT4 to a highly insulin-responsive compartment in CHO cells is modulated by culture conditions. In particular, we find that amino acids regulate distribution of GLUT4 to this kinetically defined compartment through a rapamycin-sensitive pathway. Amino acids also modulate the magnitude of insulin-stimulated translocation in 3T3-L1 adipocytes. Our results indicate a novel link between glucose and amino acid metabolism.

Closed suction surgical wound drainage after orthopaedic surgery.

BACKGROUND: Closed suction drainage systems are frequently used to drain fluids, particularly blood, from surgical wounds. The aim of these systems is to reduce the occurrence of wound haematomas and infection. OBJECTIVES: To evaluate the effectiveness of closed suction drainage systems for orthopaedic surgery. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2006), and contacted the Cochrane Wounds Group. We also searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 1), and MEDLINE (1966 to March 2006). Articles of all languages were considered. SELECTION CRITERIA: All randomised or quasi-randomised trials comparing the use of closed suction drainage systems with no drainage systems for all types of elective and emergency orthopaedic surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, using a nine item scale, and extracted data. Where appropriate, results of comparable studies were pooled. MAIN RESULTS: Thirty-six studies involving 5464 participants with 5697 surgical wounds were identified. The types of surgery involved were hip and knee replacement, shoulder surgery, hip fracture surgery, spinal surgery, cruciate ligament reconstruction, open meniscectomy and fracture fixation surgery. Pooling of results indicated no statistically significant difference in the incidence of wound infection, haematoma, dehiscence or re-operations between those allocated to drains and the un-drained wounds. Blood transfusion was required more frequently in those who received drains. The need for reinforcement of wound dressings and the occurrence of bruising were more common in the group without drains. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to support the routine use of closed suction drainage in orthopaedic surgery. Further randomised trials with larger patient numbers are required for different operations before definite conclusions can be made for all types of orthopaedic operations.

Closed suction surgical wound drainage after anterior cruciate ligament reconstruction: a systematic review of randomised controlled trials.

There is still debate over the use of drains following anterior cruciate ligament reconstruction surgery. We have performed a systematic review of the literature for randomised trials that related to the use of closed suction drains following anterior cruciate ligament reconstruction surgery. Five studies involving 349 patients were identified. There was no significant difference in the occurrence of wound healing complications, infections or the number of aspirations for haemarthrosis. There was also no difference in post-operative range of movement, functional score or incidence of limb swelling. The difference in pain scores varied between authors with some reporting increased pain in the drained group. All other outcomes reported failed to show any benefit for the use of drains. The authors recommend not using a drain following anterior cruciate ligament reconstruction with either Bone-Patellar Tendon-Bone or Quadrupled Hamstring graft.

Age of first exposure to American football and long-term neuropsychiatric and cognitive outcomes.

Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES)). Outcomes were continuous and dichotomized as clinically impaired. AFE was dichotomized into <12 and ⩾12, and examined continuously. Multivariate mixed-effect regressions controlling for age, education and duration of play showed AFE to football before age 12 corresponded with >2 × increased odds for clinically impaired scores on all measures but BTACT: (odds ratio (OR), 95% confidence interval (CI): BRI, 2.16,1.19-3.91; MI, 2.10,1.17-3.76; CES-D, 3.08,1.65-5.76; AES, 2.39,1.32-4.32). Younger AFE predicted increased odds for clinical impairment on the AES (OR, 95% CI: 0.86, 0.76-0.97) and CES-D (OR, 95% CI: 0.85, 0.74-0.97). There was no interaction between AFE and highest level of play. Younger AFE to football, before age 12 in particular, was associated with increased odds for impairment in self-reported neuropsychiatric and executive function in 214 former American football players. Longitudinal studies will inform youth football policy and safety decisions.

Re-assessing the relationship between cholesterol, statins and Alzheimer's disease.

This communication integrates the purported role of cholesterol and statins in Alzheimer's disease (AD) with recent data. Meta-analysis of association studies relevant to AD indicates that apolipoprotein (apo)E4 is the only cholesterol-related polymorphism that shows clear association with AD. This suggests that the effect of apoE4 on the pathophysiology of AD occurs via a mechanism that is not directly related to cholesterol, such as fibrillization of Abeta. Despite the lack of genetic association, cholesterol and statins clearly modulate amyloid precursor protein (APP) processing in cell culture and animal models. Statins appear to act by a pleiotropic mechanism, involving both cholesterol (via lipid rafts) and isoprenylation. The pleiotropic mechanism of statin action clarifies conflicting data from clinical studies, where statins exert an action on Abeta and AD that might be dose dependent because of actions on both cholesterol and isoprenylation. Reduced isoprenylation can also inhibit inflammation. Our own studies of brains from Alzheimer subjects +/- statins indicate that statins inhibit inflammation in humans but might not reduce cerebral Abeta load. These results suggest that the primary action of statins in humans with AD might be to reduce inflammation rather than decrease Abeta load.

A general method for identifying recessive diploid-specific mutations in Saccharomyces cerevisiae, its application to the isolation of mutants blocked at intermediate stages of meiotic prophase and characterization of a new gene SAE2.

We describe a general new approach for identifying recessive mutations that affect diploid strains of yeast Saccharomyces cerevisiae and the application of this method to the identification of mutations that confer an intermediate block in meiotic prophase chromosome metabolism. The method uses a temperature-sensitive conjugation mutation ste7-1 in combination with homothallism. The mutations of interest confer a defect in spore formation that is dependent upon a gene required for initiation of meiotic recombination and development of meiosis-specific chromosome structure (SPO11). Identified in this screen were null mutations of the DMC1 gene, nonnull mutations of RAD50 (rad50S), and mutations in three new genes designed SAE1, SAE2 and SAE3 (Sporulation in the Absence of Spo Eleven). Molecular characterization of the SAE2 gene and characterization of meiotic and mitotic phenotypes of sae2 mutants are also presented. The phenotypes conferred by a sae2 null mutation are virtually indistinguishable from those conferred by the previously identified nonnull mutations of RAD50 (rad50S). Most notably, both mutations confer only weak sensitivity to the radiomimetic agent methyl methane sulfonate (MMS) but completely block resection and turnover of meiosis-specific double-strand breaks. These observations provide further evidence that this constellation of phenotypes identifies a specific molecular function.

Mutations in Saccharomyces cerevisiae that block meiotic prophase chromosome metabolism and confer cell cycle arrest at pachytene identify two new meiosis-specific genes SAE1 and SAE3.

Two new meiosis-specific genes, SAE1 and SAE3, have been identified in a screen for mutations that confer an intermediate block in meiotic prophase. Such mutations confer a block to spore formation that is circumvented by addition of a mutation that eliminates meiotic recombination initiation and other aspects of chromosome metabolism, i.e., spo11. We show that sae1-1 and sae3-1 mutations each confer a distinct defect in meiotic recombination. sae1-1 produces recombinants but very slowly and ultimately to less than half the wild-type level; sae3-1 makes persistent hyper-resected meiotic double-strand breaks and has a severe defect in formation of recombinants. Both mutants arrest at the pachytene stage of meiotic prophase, sae1-1 temporarily and sae3-1 permanently. The phenotypes conferred by sae3-1 are similar to those conferred by mutation of the yeast RecA homologue DMC1, suggesting that SAE3 and DMC1 act at the same step(s) of chromosome metabolism. These results provide further evidence that intermediate blocks to prophase chromosome metabolism cause cell-cycle arrest. SAE1 encodes a 208-residue protein homologous to vertebrate mRNA cap-binding protein 20. SAE3 corresponds to a meiosis-specific RNA encoding an unusually short open reading frame of 50 codons.

Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration.

BACKGROUND: Caregiver exhaustion is a frequent consequence of sleep disturbance and rest-activity rhythm disruption that occurs in dementia. This exhaustion is the causal factor most frequently cited by caregivers in making the decision to institutionalize patients with dementia. Recent studies have implicated dysfunction of the circadian pacemaker in the etiology of these disturbances in dementia. METHODS: We studied the activity and core-body temperature rhythms in a cohort of 38 male patients with a clinical diagnosis of probable Alzheimer disease (AD) approximately 2 years before death. These patients were later given a confirmed diagnosis of AD (n = 23), frontotemporal degeneration (FTD) (n = 9), or diffuse Lewy body disease (DLB) with mixed AD or FTD pathologies (n = 6) after autopsy and neuropathological examination. Physiological rhythms of patients with AD and FTD were then compared with a group of normal, elderly men (n = 8) from the community. RESULTS: Alzheimer patients showed increased nocturnal activity and a significant phase-delay in their rhythms of core-body temperature and activity compared with patients with FTD and controls. The activity rhythm of FTD patients was highly fragmented and phase-advanced in comparison with controls and apparently uncoupled from the rhythm of core-body temperature. CONCLUSIONS: Patients with AD and patients with FTD show different disturbances in their rhythms of activity and temperature compared with each other and with normal elderly patients.

Use of bacteriophages in combination with competitive exclusion to reduce Salmonella from infected chickens.

Salmonella-spedfic bacteriophages (BP) and competitive exclusion (CE) were used to reduce Salmonella colonization in experimentally infected chickens. A "cocktail" of distinct phage (i.e., phage showing different host ranges and inducing different types of plaques on Salmonella Typhimurium [ST] cultures) was developed. The killing activity of the selected BPs on ST cultures differed significantly, as determined in in vitro killing assays. BPs were administered orally to the chickens several days prior and after ST challenge but not simultaneously. BPs were readily isolated from the feces of the BP-treated chickens approximately 48 hr after administration. A CE product consisting of a defined culture of seven different microbial species was used either alone or in combination with BP treatment. CE was administered orally at hatch. Salmonella counts in intestine, ceca, and a pool of liver/spleen were evaluated in Salmonella-challenged chickens treated with BP or with BP and CE. In both trials 1 and 2, a beneficial effect of the phage treatment on weight gain performance was evident. A reduction in Salmonella counts was detected in cecum and ileum of BP-, CE-, and BP+CE-treated chickens as compared with nontreated birds. In trial 1, BP treatment reduced ST counts to marginal levels in the ileum and reduced counts sixfold in the ceca. A reduction of Salmonella counts with BP, CE, and BP+CE treatments was evident in chickens from trial 2. Both CE and BP treatments showed differences in the reduction of Salmonella counts after challenge between spedmens obtained at days 4 and 14 postchallenge in ceca, liver/spleen, and ileum. The preliminary data presented in this report show that isolation and characterization of Salmonella-specific BP is uncomplicated and feasible on a larger scale. Results indicate a protective effect of both Salmonella-specific BPs and a defined competitive exclusion product against Salmonella colonization of experimentally infected chickens. These results are encouraging for further work on the use of BP as an effective alternative to antibiotics to reduce Salmonella infections in poultry.

The effects of maternal immunity and age structure on population immunity to measles.

Measles was successfully eradicated in the Pan-American Health Region in 2002. However, maintenance of elimination in parts of Africa, Europe, the USA, and other regions is proving difficult, despite apparently high vaccine coverage. This may be due to the different age structure in developed and developing populations, as well as to differences in the duration of maternal immunity. We explore the interaction between maternal immunity and age structure and quantify the resulting immunity gap between vaccine coverage and population immunity; we use this immunity gap as a novel metric of vaccine program success as it highlights the difference between actual and estimated immunity. We find that, for some combinations of maternal immunity and age structure, the accepted herd immunity threshold is not maintainable with a single-dose vaccine strategy for any combination of target age and coverage. In all cases, the herd immunity threshold is more difficult to maintain in a population with developing age structure. True population immunity is always improved if the target age at vaccination is chosen for the specific combination of maternal immunity and age structure.

MyD88 dependence of beryllium-induced dendritic cell trafficking and CD4⁺ T-cell priming.

Beryllium exposure results in beryllium hypersensitivity in a subset of exposed individuals, leading to granulomatous inflammation and fibrosis in the lung. In addition to its antigenic properties, beryllium has potent adjuvant activity that contributes to sensitization via unknown pathways. Here we show that beryllium induces cellular death and release of interleukin (IL)-1α and DNA into the lung. Release of IL-1α was inflammasome independent and required for beryllium-induced neutrophil recruitment into the lung. Beryllium enhanced classical dendritic cell (cDC) migration from the lung to draining lymph nodes (LNs) in an IL-1R-independent manner, and the accumulation of activated cDCs in the LN was associated with increased priming of CD4(+) T cells. DC migration was reduced in Toll-like receptor 9 knockout (TLR9KO) mice; however, cDCs in the LNs of TLR9-deficient mice were highly activated, suggesting a role for more than one innate receptor in the effects on DCs. The adjuvant effects of beryllium on CD4(+) T-cell priming were similar in wild-type, IL-1R-, caspase-1-, TLR2-, TLR4-, TLR7-, and TLR9-deficient mice. In contrast, DC migration, activation, and the adjuvant effects of beryllium were significantly reduced in myeloid differentiation primary response gene 88 knockout (MyD88KO) mice. Collectively, these data suggest that beryllium exposure results in the release of damage-associated molecular patterns that engage MyD88-dependent receptors to enhance pulmonary DC function.