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James Walker, John Lee and Stephen Broadberry synthesise and analyse ancient sources to address three fascinating questions: What can Domesday Book tell us about medieval England and Wales? How can we estimate medieval populations? What was the size of the medieval economy?

SARS-CoV-2 antibody levels associated with reduced hospitalization risk remain undefined. Our outpatient COVID-19 convalescent plasma (CCP), placebo-controlled trial observed SARS-CoV-2 antibody levels decreasing 22-fold from matched donor units into post-transfusion seronegative recipients. Unvaccinated recipients were jointly stratified by a) early or late transfusion (≤ 5 or >5 days from symptom onset) and b) high or low post-transfusion SARS-CoV-2 antibody levels (< or ≥ geometric mean). Early treatment with high post-transfusion antibody levels reduced hospitalization risk-0/102 (0%) compared to all other CCP recipients-17/370 (4.6%; Fisher exact p=0.03) and to all control plasma recipients-35/461 (7.6%; Fisher exact p=0.001). A similar donor upper/lower antibody level and early late transfusion stratified analyses indicated significant hospital risk reduction. Pre-transfusion nasal viral loads were similar in CCP and control recipients regardless of hospitalization outcome. Therapeutic CCP should comprise the upper 30% of donor antibody levels to provide effective outpatient use for immunocompromised and immunocompetent outpatients.

PB2452, a neutralizing monoclonal antibody fragment that binds the antiplatelet drug ticagrelor with high affinity, is being developed as a ticagrelor reversal agent. To identify a clinically useful intravenous (i.v.) reversal regimen, a semimechanistic exposure‐response model was developed during the PB2452 first‐in‐human phase I study. From a randomized, double‐blind, placebo‐controlled, single‐dose trial to evaluate the safety, efficacy, and pharmacokinetics (PKs) of PB2452 in 61 healthy volunteers pretreated with ticagrelor, sequential dose cohort data were used to build and refine an exposure‐response model that combined population PK models for ticagrelor (TICA), ticagrelor active metabolite (TAM), and PB2452, and related their binding relationships to the PK of uncomplexed TICA and TAM which is predictive of platelet inhibition. Platelet function was assessed by multiple assays. The model was developed using Bayesian methods in NONMEM. Human PK and pharmacodynamic data from sequential dose cohorts were used to initially define and then refine model parameters. Model simulations indicated that an initial i.v. bolus of PB2452, followed by a high‐rate infusion, and then a slower‐rate infusion would provide immediate and sustained reversal of the antiplatelet effects of ticagrelor. Based on model predictions, a 6 g i.v. bolus followed by 6 g infused over 4 h and then 6 g over 12 h was identified and tested in study subjects and shown to provide complete reversal within 5 min of infusion onset that was sustained for 20–24 h. The model is predictive of the reversal profile of PB2452 and will inform future trials of PB2452.

Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5–8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

Inhalation anthrax has three clinical stages: early-prodromal, intermediate-progressive, and late-fulminant. We report the comprehensive characterization of anthrax toxins, including total protective antigen (PA), total lethal factor (LF), total edema factor (EF), and their toxin complexes, lethal toxin and edema toxin in plasma, during the course of inhalation anthrax in 23 cynomolgus macaques. The toxin kinetics were predominantly triphasic with an early rise (phase-1), a plateau/decline (phase-2), and a final rapid rise (phase-3). Eleven animals had shorter survival times, mean±standard deviation of 58.7±7.6 hours (fast progression), 11 animals had longer survival times, 113±34.4 hours (slow progression), and one animal survived. Median (lower–upper quartile) LF levels at the end-of-phase-1 were significantly higher in animals with fast progression [138 (54.9–326) ng/mL], than in those with slow progression [23.8 (15.6–26.3) ng/mL] (p = 0.0002), and the survivor (11.1 ng/mL). The differences were also observed for other toxins and bacteremia. Animals with slow progression had an extended phase-2 plateau, with low variability of LF levels across all time points and animals. Characterization of phase-2 toxin levels defined upper thresholds; critical levels for exiting phase-2 and entering the critical phase-3, 342 ng/mL (PA), 35.8 ng/mL (LF), and 1.10 ng/mL (EF). The thresholds were exceeded earlier in animals with fast progression (38.5±7.4 hours) and later in animals with slow progression (78.7±15.2 hours). Once the threshold was passed, toxin levels rose rapidly in both groups to the terminal stage. The time from threshold to terminal was rapid and similar; 20.8±7.4 hours for fast and 19.9±7.5 hours for slow progression. The three toxemic phases were aligned with the three clinical stages of anthrax for fast and slow progression which showed that anthrax progression is toxin- rather than time-dependent. This first comprehensive evaluation of anthrax toxins provides new insights into disease progression.

Ticagrelor is an oral P2YIn this randomized, double-blind, placebo-controlled, phase 1 trial, we evaluated intravenous PB2452, a monoclonal antibody fragment that binds ticagrelor with high affinity, as a ticagrelor reversal agent. We assessed platelet function in healthy volunteers before and after 48 hours of ticagrelor pretreatment and again after the administration of PB2452 or placebo. Platelet function was assessed with the use of light transmission aggregometry, a point-of-care P2YOf the 64 volunteers who underwent randomization, 48 were assigned to receive PB2452 and 16 to receive placebo. After 48 hours of ticagrelor pretreatment, platelet aggregation was suppressed by approximately 80%. PB2452 administered as an initial intravenous bolus followed by a prolonged infusion (8, 12, or 16 hours) was associated with a significantly greater increase in platelet function than placebo, as measured by multiple assays. Ticagrelor reversal occurred within 5 minutes after the initiation of PB2452 and was sustained for more than 20 hours (P0.001 after Bonferroni adjustment across all time points for all assays). There was no evidence of a rebound in platelet activity after drug cessation. Adverse events related to the trial drug were limited mainly to issues involving the infusion site.In healthy volunteers, the administration of PB2452, a specific reversal agent for ticagrelor, provided immediate and sustained reversal of the antiplatelet effects of ticagrelor, as measured by multiple assays. (Funded by PhaseBio Pharmaceuticals; ClinicalTrials.gov number, NCT03492385.).

The Ebola virus disease outbreak that occurred in Western Africa from 2013–2016, and subsequent smaller but increasingly frequent outbreaks of Ebola virus disease in recent years, spurred an unprecedented effort to develop and deploy effective vaccines, therapeutics, and diagnostics. This effort led to the U.S. regulatory approval of a diagnostic test, two vaccines, and two therapeutics for Ebola virus disease indications. Moreover, the establishment of fieldable diagnostic tests improved the speed with which patients can be diagnosed and public health resources mobilized. The United States government has played and continues to play a key role in funding and coordinating these medical countermeasure efforts. Here, we describe the coordinated U.S. government response to develop medical countermeasures for Ebola virus disease and we identify lessons learned that may improve future efforts to develop and deploy effective countermeasures against other filoviruses, such as Sudan virus and Marburg virus.

Aldosterone is an important mineralocorticoid responsible for fluid and electrolyte homeostasis produced by aldosterone synthase (CYP11B2). An aldosterone synthase inhibitor (ASI) may be a therapeutic option for primary aldosteronism-related conditions such as resistant hypertension. An ASI with sufficient selectivity for CYP11B2 versus the similar cortisol-producing enzyme CYP11B1 has remained elusive. PB6440 is a novel ASI that is potent and highly selective for CYP11B2. In vitro studies demonstrated 200-300-fold selectivity of PB6440 for human CYP11B2 compared to human CYP11B1. In single and multiple dose cynomolgus monkey studies of orally administered PB6440, dose-and concentration-dependent reduction of plasma aldosterone after ACTH challenge was observed with >90% reduction at higher doses. Consistent with its high selectivity, PB6440 had little effect on the CYP11B1 cortisol pathway. Plasma levels of cortisol, 11-deoxycortisol, and deoxycorticosterone, remained unchanged even at high doses of PB6440. Systolic and diastolic blood pressure was reduced in a dose-dependent manner. Circulating half-life of PB6440 was approximately 17 hours with high oral bioavailability. In summary, PB6440 is a highly selective ASI that demonstrated sustained aldosterone suppression for 14 days with no effect on the CYP11B1 pathway in non-human primates. In single and multiple dose studies, PB6440 appeared well tolerated, demonstrating good oral bioavailability, and a PK profile supportive of once daily dosing. These results suggest that PB6440 may be useful in humans as a novel therapeutic for treating hypertension or other conditions caused by excess aldosterone.

In 2017, 43.9% of US physicians reported symptoms of burnout. Poor electronic health record (EHR) usability and time-consuming data entry contribute to burnout. However, less is known about how modifiable dimensions of EHR use relate to burnout and how these associations vary by medical specialty. Using the KLAS Arch Collaborative’s large-scale nationwide physician (MD/DO) data, we used ordinal logistic regression to analyze associations between self-reported burnout and after-hours charting and organizational EHR support. We examined how these relationships differ by medical specialty, adjusting for confounders. Physicians reporting ≤ 5 hours weekly of after-hours charting were twice as likely to report lower burnout scores compared to those charting ≥6 hours (aOR: 2.43, 95% CI: 2.30, 2.57). Physicians who agree that their organization has done a great job with EHR implementation, training, and support (aOR: 2.14, 95% CI: 2.01, 2.28) were also twice as likely to report lower scores on the burnout survey question compared to those who disagree. Efforts to reduce after-hours charting and improve organizational EHR support could help address physician burnout.

Unimolecular decomposition pathways are challenging to address in transition-metal catalysis and have previously not been suppressed via incorporation into a solid support. Two robust metal-organic frameworks (IRMOF-10 and bio-MOF-100) are used for the architectural stabilization of a structurally well-defined gold(III) catalyst. The inherent rigidity of these materials is utilized to preclude a unimolecular decomposition pathway - reductive elimination. Through this architectural stabilization strategy, decomposition of the incorporated gold(III) catalyst in the metal-organic frameworks is not observed; in contrast, the homogeneous analogue is prone to decomposition in solution. Stabilization of the catalyst in these metal-organic frameworks precludes leaching and enables recyclability, which is crucial for productive heterogeneous catalysis.

One of the most important manuscripts surviving from thirteenth-century England, the corpus of documents known as the Hundred Rolls for Cambridge have been incomplete until the recent discovery of an additional roll. This invaluable volume replaces the previous inaccurate transcription by the record commission of 1818 and provides new translations and additional appendices. Shedding new light on important facets of business activity in thirteenth-century Cambridge, this volume makes a significant contribution to our knowledge of the early phases of capitalism. This unique text will be of interest to anyone working in the fields of economic and business history, entrepreneurship, philanthropy and medieval studies. A research monograph based on recently discovered historical documents, Compassionate Capitalism: Business and Community in Medieval England, by Casson et al, is also now available from Bristol University Press.

The chapter provides new translations of these previously unpublished documents.

This chapter sets out the key research questions addressed in the book. These concern the role of English towns in the commercial revolution that was underway in the thirteenth century. There is a particular focus on the medieval property market, and on the citizens who were active in that market. The chapter reviews previous literature, and explains the choice of Cambridge as a case study. This choice is largely dictated by a unique source of information, namely the Cambridge Hundred Rolls, which are also described in this chapter. The Hundred Rolls date to 1279, but the origins of the town were much earlier. The early history of the town is set out, so that the context of the Hundred Rolls can be fully understood.

The Rotuli Hundredorum, better known as the Hundred Rolls, contain 1,800 pages of statistical information relating to property rents in c.1279 for King Edward I. A printed edition was published by the Record Commission in 1818, using the original medieval Latin, in a special typeface designed to replicate the abbreviated script of medieval scribes. It is this edition that has formed the basis for most (though not all) subsequent research on property holding at that time....

Family dynasties were important players in the property market of medieval Cambridge, the Hundred Rolls reveal. Using a wide range of archival sources this chapter examines the inter family relationships and cross family connections of 23 families identified from the rolls, including the Bartons, Blancgernuns and Dunnings. Strategies by which families accumulated and extended their property portfolios are examined. Causes of family decline and family success are considered.

Chapter 3 analyses the economic topography of the town, building on the results presented in Chapter 2. It investigates how far occupations were specialised in different part of the town. It constructs profiles of all the Cambridge parishes, showing how many properties were located in each, how much rent those properties paid, to whom they paid it, who held the properties, and in some cases their occupation too. It is also possible to chart the spatial distribution of occupational names. Because of the missing roll, it is possible for the first time to provide a definitive account of all the parishes. This corrects a bias in previous topographical accounts, which have over-emphasised the north and west of the town at the expense of the south and east.

Chapter 8 outlines five key findings from the book: the importance of property transactions, the significance of urban topography, the importance of the family, the importance of charitable giving to institutions and the significance of the regional and national context.

Haemaphysalis longicornis, the cattle tick or bush tick, has an extended distribution throughout Asia and the Pacific region, including China, Russia, the Republic of Korea (ROK), Japan, Australia, New Zealand, and the South Pacific islands. It is an obligate ectoparasite found commonly on medium to large sized wild and domestic animals, with humans as an accidental host. Haemaphysalis longicornis transmits a number of pathogens, including severe fever with thrombocytopenia syndrome and tick-borne encephalitis viruses, bacteria, helminths, and protozoans, that impact on veterinary (wild and domestic animals) and human health. Surveys of rickettsial pathogens associated with H. longicornis from China, the ROK, and Japan have resulted in the discovery of more than 35 incompletely characterized molecular isolates of Rickettsia. In response to the increased global threat of tick-borne rickettsial diseases, H. longicornis collected in the ROK and China were assessed in our laboratory and two additional Rickettsia spp. isolates (ROK-HL727 and XinXian HL9) were identified. These agents were fully characterized by multilocus sequence typing using partial gene fragment sequences of rrs, gltA, ompA, ompB, and sca4. Phylogenetic comparisons of these Rickettsia isolates with known Rickettsia species and other molecular isolates identified from H. longicornis were performed to better understand their interrelationships. Phylogenetic analysis of the sequences from these 5 gene fragments showed that ROK-HL727 was closely related to rickettsial isolates of H. longicornis previously reported from China, the ROK and Japan, but distinct from any currently recognized Rickettsia species. It therefore qualifies genetically as a new species, introduced herein as Candidatus Rickettsia longicornii. The XinXian-HL9 isolate detected from China was determined to be genetically similar to the human pathogen Rickettsia heilongjiangensis. People living and working in areas where H. longicornis is endemic should be aware of the potential for rickettsial diseases.

Aims The aims of the present study were to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class factor XIa inhibitor, in Japanese and non-Japanese healthy subjects. Methods This was a randomized, placebo-controlled, double-blind, sequential, ascending-dose study of 2-h (part A) and 5-day (part B) intravenous (IV) infusions of BMS-962212. Part A used four doses (1.5, 4, 10 and 25 mg h-1 ) of BMS-962212 or placebo in a 6:2 ratio per dose. Part B used four doses (1, 3, 9 and 20 mg h-1 ) enrolling Japanese (n = 4 active, n = 1 placebo) and non-Japanese (n = 4 active, n = 1 placebo) subjects per dose. The PK, PD, safety and tolerability were assessed throughout the study. Results BMS-962212 was well tolerated; there were no signs of bleeding, and adverse events were mild. In parts A and B, BMS-962212 demonstrated dose proportionality. The mean half-life in parts A and B ranged from 2.04 to 4.94 h and 6.22 to 8.65 h, respectively. Exposure-dependent changes were observed in the PD parameters, activated partial thromboplastin time (aPTT) and factor XI clotting activity (FXI:C). The maximum mean aPTT and FXI:C change from baseline at 20 mg h-1 in part B was 92% and 90%, respectively. No difference was observed in weight-corrected steady-state concentrations, aPTT or FXI:C between Japanese and non-Japanese subjects (P > 0.05). Conclusion BMS-962212 has tolerability, PK and PD properties suitable for investigational use as an acute antithrombotic agent in Japanese or non-Japanese subjects.

Hypertension is associated with high morbidity and mortality. Blood pressure (BP) levels vary widely due to predictable biological rhythms and unpredictable environmental factors. Daily (circadian) rhythm characteristics are considered essential parameters for recognizing and treating increased risks in BP. Franz Halberg spent most of his academic career in cardiovascular research, focused on ambulatory monitoring and developing chronobiological methods for clinical application. To compare BP Variability (BPV), automatically monitored ambulatory BP around the clock at 30-60 min intervals in 20 human subjects was compared with telemetered circadian BP in rats after one-cell homozygous embryo-transfer into spontaneously hypertensive (SHR, pup:shr) or normotensive (WKY, pup:wky) rats' oviducts (embryos: s,w; oviduct-uterus: S,W) and cross-suckled at birth (nurses S,W). The circadian response peaked in the late afternoon hours in most human subjects and early morning hours in rats. Human circadian double amplitudes (2A) varied from 8 to 26 mm Hg with higher 2A in elder adults, and 3-8 mm Hg in rats with significantly higher fluctuations in SHR groups (7.5±0.7 for sSS, 8.3±0.6 for sSW vs. 4.7±0.3 mm Hg for wWW). The circaseptan 2A in the adolescents were 10±1 for SBP and 12±3 mm Hg for DBP, and sharp increased winter 2A (SBP 54; HR 48, both P

The development of LXR agonists for the treatment of coronary artery disease has been challenged by undesirable properties in animal models. Here we show the effects of an LXR agonist on lipid and lipoprotein metabolism and neutrophils in human subjects. BMS-852927, a novel LXRβ-selective compound, had favorable profiles in animal models with a wide therapeutic index in cynomolgus monkeys and mice. In healthy subjects and hypercholesterolemic patients, reverse cholesterol transport pathways were induced similarly to that in animal models. However, increased plasma and hepatic TG, plasma LDL-C, apoB, apoE, and CETP and decreased circulating neutrophils were also evident. Furthermore, similar increases in LDL-C were observed in normocholesterolemic subjects and statin-treated patients. The primate model markedly underestimated human lipogenic responses and did not predict human neutrophil effects. These studies demonstrate both beneficial and adverse LXR agonist clinical responses and emphasize the importance of further translational research in this area.

Commemoration can take the form of an action – a calling to remembrance, such as through prayer, or the form of an object – such as a memorial. Many studies of late medieval commemoration have tended to examine the latter, exploring particular monuments in particular contexts, mostly in churches and cathedrals, as well as considering different workshops, styles and patrons. They have focused on the product of commemoration. Most have taken a traditional approach to this subject, simply discussing the tomb, or the window, or the chantry without reflecting on the overall message. There were, however, a myriad of different commemorative enterprises available. The role of the monument in the context of remembrance, the benefactor, charity and prayer is here explored within the university town of Cambridge. Studies of towns, such as Bristol, are well known and in recent years there has been a revived interest in urban commemoration which has ‘opened up’ ideas on the bigger picture and how intercessory prayer dovetailed with investment in church building, most particularly the monument, to achieve salvation. New material on Boston, Coventry and York has revealed how urban elites and visitors sought appropriate commemorations for themselves and their families through a variety of differing and inter-connected strategies, while in London Christian Steer's study of St. James Garlickhithe has pieced together parts of the ‘commemoration jigsaw’ within this particular city parish, in which different forms of commemoration served the interests of the living and the dead. Individual monuments, too, are now receiving fresh interpretations. In medieval Cambridge, the range of religious institutions to which benefactors could make gifts and entrust their commemoration expanded significantly. A burgess living in the town shortly after 1200 could choose to make a benefaction to one of sixteen parish churches, to either religious house (or both), or to one of the two hospitals. By 1300, Cambridge residents could also select one (or more) of the six houses of mendicant friars, or another religious house or hospital, as possible recipients. By 1400, wealthy Cambridge citizens could also choose one of many guilds or several academic colleges to provide their intercessory services. Patterns of benefaction among medieval townspeople generally followed these trends, with new institutions commonly becoming the chief objects of attention. The town was distinctive in having the presence of an academic community which grew in size and wealth during the later Middle Ages.

Blood pressure (BP) fluctuates due to complex interactions between genetic factors and environmental stimulation. BP variability (BPV) is a physiological phenomenon, as a measure of hemodynamic conditions reflected in the autonomic nervous system. Daily (circadian) rhythms as biological time structures are considered essential parameters for recognizing and treating BP risk factors. Thus, ambulatory BP and heart rate (HR) were monitored (ABPM) in 11 normotensive (NT) in a free living, and 13 borderline hypertensive (BH) adults with Na and weight (WT, Kg) interventions in a freely moving lab environments, around the clock at 30-minute to hourly intervals. In the intervention study, circadian BP, HR, urinary aldosterone (Aldo, μg/h), creatinine (Cr), Na, K in mEq/h and Na/K ratio were compared. Data was analyzed by the linear least square rhythmometry method. All subjects showed significant circadian fluctuations in BP (mm Hg) and HR (beats/min). The circadian response peaked in the noon to late afternoon hours in the NT and in the reference stage of the intervention study. In NT, SBP: 111±2 with variability 14.6% and peak hr at 16:00; DBP: 74.0±1 with variability 16.0% and peak hr at 15:40; and HR: 64.3±2 with peak hr at 16:96 (-254°). In the intervention study with reference (I), Na restriction (II) and weight (WT) reduction (III) stages, SBP: 130±3.7; 130±1.7; 116±1.7 with variability (SBPV), 27.5, 31.4, and 25.4%; peak hrs at 16:26, 13:52; 12:24, respectively; DBP: 85±2.3; 83±2.2; 77±1.9 with variability (DBPV), 21.1, 26.4, 33.5%; peak hrs at 16:15, 18:29, 07:52, respectively; and HR: 64±2.1; 61±2.1; 66±2.3 with HRV, 30.2, 34.6, 28.3%; peak hrs at 15:07; 14:64, 14:55, respectively. Circadian UAldo: 0.63, 0.73, 0.58; UNa: 6.3, 2.9, 3.5; UK: 3.1, 3.1, 2.9; and WT: 89.9, 87.8, 83.2 in I, II, and III study stages, respectively. Thus, BP and HR, and their variabilities are the factors readjusted in the Na and WT reductions, and the peak shifted to earlier hours in the intervention. The variability, in the reference stage already higher than the NT levels, was not favorably changed with Na and WT interventions, although BP was normalized, especially following the WT reduction. Increased or shallow amplitudes may be predictive risk factors of vascular disease.

A clear and accessibly written guide to the medieval cloth-making trade in England.

It is widely believed that a preceptory (house and estate centre) of the Knights Templar was located in the township of Whitley, near Selby, only four miles from another preceptory at Temple Hirst. This article argues that documentary evidence, closely analysed, points to the site of the preceptory being 24 miles further east, at Weedley, near South Cave in the East Riding. The evidence includes references to lands at Wichele or Withele in the Templars’ inquest of 1185, and an inventory detailing possessions of the preceptory of Wythele in 1308. The location of the preceptory is examined alongside the changing organization of the Templars’ estates by the early-fourteenth century. Establishing the correct location of the preceptory is important in understanding more about the relationship between different Templar houses within the county, and highlights the potential for archaeological remains at the site of the preceptory.

Enteric bacteria, such as Escherichia coli , are exposed to a variety of stresses in the nonhost environment. The development of biofilms provides E. coli with resistance to environmental insults, such as desiccation and bleach. We found that biofilm formation, specifically production of the matrix components curli and cellulose, protected E. coli against killing by the soil-dwelling nematode Caenorhabditis elegans and the predatory bacterium Myxococcus xanthus . Additionally, matrix-encased bacteria at the air-biofilm interface exhibited ∼40-fold-increased survival after C. elegans and M. xanthus killing compared to the non-matrix-encased cells that populate the interior of the biofilm. To determine if nonhost Enterobacteriaceae reservoirs supported biofilm formation, we grew E. coli on media composed of pig dung or commonly contaminated foods, such as beef, chicken, and spinach. Each of these medium types provided a nutritional environment that supported matrix production and biofilm formation. Altogether, we showed that common, nonhost reservoirs of E. coli supported the formation of biofilms that subsequently protected E. coli against predation.

Background Helicobacter pylori (H. pylori) testing in patients with bleeding ulcers is recommended by society guidelines and considered a quality indicator. The aim of the study is to examine the proportion of patients with bleeding ulcers who had H. pylori testing and identify predictors associated with H. pylori testing. Materials and methods Consecutive hospitalized patients with bleeding ulcers documented endoscopically at a single center from 10/2004-5/2011 were identified retrospectively from an endoscopy database. The proportion of patients undergoing direct H. pylori testing (histology, rapid urease test, breath test or stool antigen) and any H. pylori testing (direct or serologic) were determined. Results Among 330 patients with bleeding ulcers, 105 (32%, 95% CI 27–37%) underwent direct testing and another 52 (16%, 95% CI 12–20%) had serologic testing during a median follow-up of 9 months (range, 0–86). H. pylori testing occurred at the index hospitalization in 146 (93%) of the 157 patients tested. Among the 105 patients who had direct H. pylori testing, 90 (86%) had biopsy-based testing during the initial endoscopy. On multivariate analysis, undergoing biopsy of a gastric ulcer was strongly associated with having direct H. pylori testing performed (OR = 5.1, 95% CI 2.3–11.5; p

In total, 183,602 female culicine mosquitoes were captured by Mosquito Magnet, black light, and New Jersey light traps, and manual aspiration of resting blood-fed mosquitoes, in the Republic of Korea from 2008 to 2011. Culicine mosquitoes were identified to species, placed in pools of up to 30 mosquitoes each, and screened for flavivirus RNA by using an SYBR green I-based reverse transcription-polymerase chain reaction assay. Thirty-two of the 8,199 pools assayed were positive by quantitative polymerase chain reaction for Chaoyang virus (CHAOV), an insect-specific virus [26 Aedes vexans nipponii Theobald, 3 Culex pipiens L., 1 Aedes albopictus (Skuse), 1 Aedes bekkui Mogi, and 1 Armigeres subalbatus (Coquillett)]. The maximum likelihood estimations (estimated number of virus-positive mosquitoes/1,000 mosquitoes) for Ae. bekkui, Ae. albopictus, Ar. subalbatus, Ae. vexans nipponii, and Cx. pipiens positive for CHAOV were 5.37, 3.29, 0.77, 0.27, and 0.26, respectively. CHAOV is an insect-specific virus, and there is currently no evidence to suggest a role in animal or human disease.

Dr Franz Halberg, a towering figure in cardiovascular research who founded and developed the new science of modernized chronobiology, passed away a month shy of 94 years of age on June 9, 2013. The chronobiological vocabulary and ambulatory monitoring methods were his original conceptions. Dr Halberg’s international stature and contributions to hypertension research through chronobiological methods were monumental, and we pay our respects to this outstanding scientist, educator, and scientific father and his dedication to the advancement of heart attack and stroke victims, hypertension research through chronobiological methods in individual monitoring, analyses, and interpretation in variations as a function of Time. In the early stages of his professional life, his keen observations of biological variations in living beings enabled him to find periodicities shared between biological systems and their broad environments, influenced by the sun and the cosmos, leading to chronomics (broad time structures beyond circadian rhythms). Biological time structures (clock hours) and chronomes are considered essential parameters in blood pressure monitoring, as well as in neurohormonal rhythms and other organs/systemic variations. The impact Dr Halberg had in science stemmed not only from his original findings but also from his vision of their implications that led beyond a scientific breakthrough to a new way of thinking as a truly great scientist. His lifetime of hard work after his medical education and training seeking optimal configurations of the time structure has contributed to some of the greatest advancements in the modern scientific world and standardized clinical practice, especially in hypertension. His research on timing guided by the circadian clock observed early changes in blood pressure and heart rate variability, especially large fluctuations in amplitudes and shift changes in peak hours among heart attack and stroke victims, and cancer patients. The changed rhythms can be detected during subclinical stages by ambulatory monitoring, …

Tembusu virus (TMUV; Ntaya serocomplex) was detected in two pools of mosquitoes captured near Sangkhlaburi, Thailand, as well as from sera from sentinel ducks from the same area. Although TMUV has been isolated from several mosquito species in Asia, no studies have ever shown competent vectors for this virus. Therefore, we allowed mosquitoes captured near Sangkhlaburi to feed on young chickens that had been infected with TMUV. These mosquitoes were tested approximately 2 weeks later to determine infection, dissemination, and transmission rates. Culex vishnui developed high viral titers after feeding on TMUV-infected chicks and readily transmitted virus to naïve chickens. In contrast, Cx. fuscocephala seemed less susceptible to infection, and more importantly, zero of five fuscocephala with a disseminated infection transmitted virus by bite, indicating a salivary gland barrier. These results provide evidence for the involvement of Culex mosquitoes in the transmission of TMUV in the environment.