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Objectives. To assess the impact of the COVID-19 pandemic on immunization services across the life course. Methods. In this retrospective study, we used Michigan immunization registry data from 2018 through September 2020 to assess the number of vaccine doses administered, number of sites providing immunization services to the Vaccines for Children population, provider location types that administer adult vaccines, and vaccination coverage for children. Results. Of 12 004 384 individual vaccine doses assessed, 48.6%, 15.6%, and 35.8% were administered to children (aged 0–8 years), adolescents (aged 9–18 years), and adults (aged 19‒105 years), respectively. Doses administered overall decreased beginning in February 2020, with peak declines observed in April 2020 (63.3%). Overall decreases in adult doses were observed in all settings except obstetrics and gynecology provider offices and pharmacies. Local health departments reported a 66.4% decrease in doses reported. For children, the total number of sites administering pediatric vaccines decreased while childhood vaccination coverage decreased 4.4% overall and 5.8% in Medicaid-enrolled children. Conclusions. The critical challenge is to return to prepandemic levels of vaccine doses administered as well as to catch up individuals for vaccinations missed. (Am J Public Health. 2021;111(11):2027–2035. https://doi.org/10.2105/AJPH.2021.306474 )

This article grapples with the problem of applying a nineteenth-century neologism to the relationships between clergy and laity within pre-Reformation Catholicism, essentially between circa...

Differences in pollen performance, often revealed during pollen competition, have long been recognized as evolutionarily significant and agriculturally important. Though we have sophisticated models for the growth of individual pollen tubes, we have few robust models for larger-scale pollen competition, a process that has been linked with inbreeding avoidance, sexual selection, reproductive barrier reinforcement and speciation. Here we use existing data on pollen performance traits to develop an agent-based model of pollen competition. We calibrate our model parameters to empirical data found in the literature of seed siring proportions from mixed pollinations and pollen tube length distributions from single-accession pollinations. In this model, parameters that influence pollen tube movement and sensing of ovules were found to be primary factors in competition. Our model also demonstrates that interference competition emerges as a property of pollen competition, and suggests a potential mechanism for this phenomenon. This study integrates pollen performance measures with mathematical modelling conducted on a simplified and accessible system. This represents the first mechanistic agent-based model for pollen competition. Our model may be extended to predict seed siring proportions for other accessions of Arabidopsis thaliana given data on their pollen performance traits.

Background: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+). Methods: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case–cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination. Results: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI, 60%–71%) for UTD, 33% (95% CI, 18%–46%) for 2 doses-not UTD, and 40% (95% CI, 27%–50%) for 1 dose. The case–cohort analysis yielded VE estimates of 72% (95% CI, 64%–79%) for UTD, 39% (95% CI, 10%–58%) for 2 doses-not UTD, and 48% (95% CI, 25%–63%) for 1 dose. VE was higher for vaccination at age Conclusions: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination. Impact: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

Late medieval Europe identified itself as explicitly Christian and specifically catholic. Christianity provided moral and ethical guidelines for organizing and structuring human society; it also presented moral and ethical challenges to contemporary social structures and practices. It accordingly provoked constant debate on issues like the violence of warfare, the validity of lending money at interest, social differentiation, and relations with other religious traditions. These were also traumatic years in the western church’s institutional history, especially for the papacy. Preceding evolutions continued and were consolidated, but there was also reaction as obscured tensions and ambiguities became more apparent, revealing fissures and forces which threatened the church’s status and its claims to catholicity within Europe. The chapter deals with a broad range of issues: the papacy; ideas about the church, the pope, and conciliarism; the evolution of national and local churches, the lower clergy, and the religious orders; and, of course, spirituality, heresy, dissent.

On March 13, 2020, the United States declared a national state of emergency to control the pandemic spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Public health response measures to mitigate the pandemic have centered on social distancing and quarantine policies, including shelter-in-place and stay-at-home orders. Michigan implemented a stay-at-home order on March 23, 2020, to facilitate social distancing (2). Such strategies might result in decreased accessibility to routine immunization services, leaving children at risk for vaccine-preventable diseases and their complications (3). To evaluate whether vaccination coverage has changed during the pandemic, data from the Michigan Care Improvement Registry (the state's immunization information system) (MCIR) were analyzed. Changes in vaccine doses administered to children and the effects of those changes on up-to-date status were examined for vaccinations recommended at milestone ages corresponding to the end of an Advisory Committee on Immunization Practices (ACIP) recommendation period for one or more vaccines (4).

Background and aims Pollen grains of flowering plants display a fascinating diversity of forms, including diverse patterns of apertures, the specialized areas on the pollen surface that commonly serve as the sites of pollen tube initiation and, therefore, might play a key role in reproduction. Although many aperture patterns exist in angiosperms, pollen with three apertures (triaperturate) constitutes the predominant pollen type found in eudicot species. The aim of this study was to explore whether having three apertures provides selective advantages over other aperture patterns in terms of pollen survival, germination and reproductive success, which could potentially explain the prevalence of triaperturate pollen among eudicots. Methods The in vivo pollen germination, pollen tube growth, longevity and competitive ability to sire seeds were compared among pollen grains of Arabidopsis thaliana with different aperture numbers. For this, an arabidopsis pollen aperture series was used, which included the triaperturate wild type, as well as mutants without an aperture (inaperturate) and with more than three apertures. Key results Aperture number appears to influence pollen grain performance. In most germination and longevity experiments, the triaperturate and inaperturate pollen grains performed better than pollen with higher aperture numbers. In mixed pollinations, in which triaperturate and inaperturate pollen were forced to compete with each other, the triaperturate pollen outperformed the inaperturate pollen. Conclusions Triaperturate pollen grains might provide the best trade-off among various pollen performance traits, thus explaining the prevalence of this morphological trait in the eudicot clade.

An exclusive focus on priests as the agents and conduits of pastoral care, with pastoralia as its medium, may canalise the concept and its analysis too much, especially as the message was received and taken into hearts in the later medieval centuries. This chapter shows that its reception generated quasi-ministerial relationships among the laity, reshaping the spiritual landscape and expanding the scope, mechanisms and responsibility of and for pastoral care. The concept of pastoral care is so much interwoven into church history and the continuing Christian traditions that its meaning seems self-evident: it is the preserve of priests and ministers, those engaged with pastoral theology. The top-down construction of pastoral care owes much to the way in which its initial summaries were promulgated. The complete catechism encapsulates ‘pastoral care’. The commonality of pastoral care established by the Spiritual Works of Mercy begins to shift the perspective in the evaluation of pastoral care in general.

The canon law dictum that ‘dubius in fide infidelis est’ offers a seemingly definitive statement on the place of doubt and uncertainty in medieval Catholicism. Yet where Catholic teaching was open to question, doubt was inseparable from faith, not merely as its obverse but as part of the process of achieving faithfulness – the trajectory outlined by Abelard in the twelfth century. The challenge for the Church was not that doubters lacked faith, but that having tested their doubts they might end up with the wrong faith: doubt preceded assurance, one way or the other. That problem is addressed in this essay by a broad examination of the ties between faith and doubt across the late Middle Ages (from the twelfth to the sixteenth centuries), arguing that uncertainty and doubt were almost unavoidable in medieval Catholicism. As the starting points in a process which could lead to heresy and despair, they also had a positive role in developing and securing orthodox faith.

Alteplase is an effective treatment for ischaemic stroke patients, and it is widely available at all primary stroke centres. The effectiveness of alteplase is highly time-dependent. Large tertiary centres have reported significant improvements in their door-to-needle (DTN) times. However, these same improvements have not been reported at community hospitals.Red Deer Regional Hospital Centre (RDRHC) is a community hospital of 370 beds that serves approximately 150,000 people in their acute stroke catchment area. The RDRHC participated in a provincial DTN improvement initiative, and implemented a streamlined algorithm for the treatment of stroke patients. During this intervention period, they implemented the following changes: early alert of an incoming acute stroke patient to the neurologist and care team, meeting the patient immediately upon arrival, parallel work processes, keeping the patient on the Emergency Medical Service stretcher to the CT scanner, and administering alteplase in the imaging area. Door-to-needle data were collected from July 2007 to December 2017.A total of 289 patients were treated from July 2007 to December 2017. In the pre-intervention period, 165 patients received alteplase and the median DTN time was 77 minutes [interquartile range (IQR): 60-103 minutes]; in the post-intervention period, 104 patients received alteplase and the median DTN time was 30 minutes (IQR: 22-42 minutes) (plt; 0.001). The annual number of patients that received alteplase increased from 9 to 29 in the pre-intervention period to annual numbers of 41 to 63 patients in the post-intervention period.Community hospitals staffed with community neurologists can achieve median DTN times of 30 minutes or less.L’altéplase est un traitement efficace dans le cas de patients victimes d’AVC ischémiques et demeure largement disponible dans les centres de soins de niveau primaire dédiés aux AVC. Cela dit, son efficacité dépend fortement des délais en fonction desquels on peut l’administrer. À cet égard, les centres de soins de niveau tertiaire ont fait état d’importantes améliorations en ce qui regarde leurs délais entre l’arrivée de patients et l’injection d’un traitement thrombolytique. Toutefois, il semble que de telles améliorations n’ont pas été signalées dans les hôpitaux communautaires.Le Red Deer Regional Hospital Centre (RDRHC) est un hôpital communautaire de 370 lits qui dessert approximativement 150 000 personnes dans sa zone d’attraction. Cet hôpital a participé à une initiative provinciale de réduction des délais mentionnés ci-dessus. Pour ce faire, il a mis au point un algorithme simplifié en vue du traitement de patients victimes d’AVC. Au cours de cette période d’intervention, les mesures de changement suivantes ont donc été adoptées : des alertes précoces transmises à un neurologue et aux équipes soignantes au moment de l’admission de patients victimes d’AVC aigus ; des rencontres immédiates avec les patients, et ce, dès leur arrivée à l’hôpital ; des processus de travail menés de façon parallèle ; le maintien des patients dans une civière d’ambulance jusqu’à temps qu’on puisse les conduire à un tomodensitomètre ; enfin, le fait d’administrer l’altéplase en fonction de la zone atteinte révélée par imagerie. Soulignons enfin que nos données en matière de réduction des délais ont été collectées de juillet 2007 à décembre 2017.Au total, 289 patients ont été traités durant cette période. Au cours de la période antérieure à l’initiative évoquée précédemment, 165 patients ont bénéficié d’un traitement à l’altéplase ; les délais médians entre l’arrivée des patients et l’injection de ce médicament thrombolytique étaient alors de 77 minutes (EI : 60-103 minutes). Une fois mise en place l’initiative de réduction des délais, 104 patients ont reçu un traitement à l’altéplase ; cette fois, les délais médians du RDRHC étaient de 30 minutes (EI : 22-42 minutes ; p0,001). Fait à noter, le nombre annuel de patients ayant bénéficié de l’altéplase est passé de 9 à 29 durant la période pré-initiative et de 41 à 63 lors de la période post-initiative.Dans le cas des hôpitaux communautaires disposant de neurologues réguliers, il est possible de parvenir à des délais de 30 minutes ou moins entre l’arrivée de patients et l’injection d’un traitement thrombolytique.

Estimation of at-sea discards is an issue that has received considerable attention worldwide. With this increasing focus, there is a need for greater precision of weight estimates for less common and fishery-limiting species. While one solution is to mandate full (100%) observer coverage to reduce uncertainty in estimation at the trip level, variance from on-deck sampling methods (e.g. within-haul) should also be properly addressed. Commercial fishing vessels are not perfect sampling platforms and all sampling methods suffer from implementation issues that potentially impact the quality of the data collected and the resulting estimates. We conducted a cooperative study with industry to evaluate two observer sampling methods on trawl vessels delivering their catch to shoreside processors. The alternative observer sampling method that targets the portion of the haul that would be discarded directly at-sea, relying on shoreside reports of retained catch to generate total catch estimates, was tested against the standard methods currently used by the NMFS North Pacific Groundfish and Halibut Observer Program that sample the entire catch, both retained and discarded portions (combined). Methods were tested simultaneously by deploying two observers to sample each haul on study trips within three Gulf of Alaska trawl fisheries that varied widely in amount and species composition of discards: Rockfish Program, arrowtooth flounder, and shallow water flatfish. Although the alternative method was successfully implemented in two of the three fisheries, logistical constraints decreased sampling effectiveness in the third. In some situations, observers were unable to collect multiple samples under both methods, preventing variance estimation. This occurred more often for the observer using standard methods. Detection of less common and rare species was higher using the alternative sampling method. Discard estimates from the two methods were found to be significantly different in two of the fisheries examined (Rockfish Program and arrowtooth flounder). Discard estimates under the alternative method tended to have smaller variances than for the standard method, although this was not universally the case. These results provide an important comparison of the relative performance of different on-deck sampling methods under varying catch conditions and fisheries.

Laboratories in introductory biology must engage and excite students in ways that effectively prepare them to succeed in upper-level courses in a field with a rapidly increasing body of knowledge. Our inquiry-based lab immerses students in the process of science by asking them to develop behavioral bioassays to test the response of aquatic macroinvertebrates to various pollutants. Students begin with literature review and hypothesis generation on an open-ended question; continue through experimental design, data collection, and analysis; and finish with writing a paper that is peer reviewed. A series of weekly lab activities serves to scaffold key skills that enable completion of the behavioral bioassays, and a final field aquatic-biomonitoring project connects lab work to real-life environmental issues. Because not much is known about how certain pollutants affect the behavior of specific aquatic invertebrates, students’ curiosity is piqued by new discovery, and instructors are engaged by the sense of partnering with students to explore the unknown. This module requires that students engage in core biological concepts, including the significance of variation in living organisms, the structure and function of organisms, and impacts of environmental change on both homeostasis and populations.

The 15th and 16th centuries are often depicted as the death throes of Latin in England, supplanted by ‘The Rise of English’. Arguing that more English did not necessarily mean less Latin, this chapter assesses the role of Latin in England from c.1400 to c.1540, and suggests that in terms of overall cultural history, use, and the accumulated inheritance from the past, this may have been when England was at its most Latinate of all. Considering the use of Latin as a spectrum of skills—reading, writing, speaking, and listening—and across a range of abilities, it offers a positive appreciation of late Medieval Latin as a vital force in a multilingual society.

Female control of nonrandom mating has never been genetically established, despite being linked to inbreeding depression and sexual selection. In order to map the loci that control female-mediated nonrandom mating, we constructed a new advanced intercross recombinant inbred line (RIL) population derived from a cross between Arabidopsis (Arabidopsis thaliana) accessions Vancouver (Van-0) and Columbia (Col-0) and mapped quantitative trait loci (QTLs) responsible for nonrandom mating and seed yield traits. We genotyped a population of 490 RILs. A subset of these lines was used to construct an expanded map of 1,061.4 centimorgans with an average interval of 6.7 ± 5.3 centimorgans between markers. QTLs were then mapped for female- and male-mediated nonrandom mating and seed yield traits. To map the genetic loci responsible for female-mediated nonrandom mating and seed yield, we performed mixed pollinations with genetically marked Col-0 pollen and Van-0 pollen on RIL pistils. To map the loci responsible for male-mediated nonrandom mating and seed yield, we performed mixed pollinations with genetically marked Col-0 and RIL pollen on Van-0 pistils. Composite interval mapping of these data identified four QTLs that control female-mediated nonrandom mating and five QTLs that control female-mediated seed yield. We also identified four QTLs that control male-mediated nonrandom mating and three QTLs that control male-mediated seed yield. Epistasis analysis indicates that several of these loci interact. To our knowledge, the results of these experiments represent the first time female-mediated nonrandom mating has been genetically defined.

Saccharomyces cerevisiae ergosterol biosynthesis, like cholesterol biosynthesis in mammals, is regulated at the transcriptional level by a sterol feedback mechanism. Yeast studies defined a 7-bp consensus sterol-response element (SRE) common to genes involved in sterol biosynthesis and two transcription factors, Upc2 and Ecm22, which direct transcription of sterol biosynthetic genes. The 7-bp consensus SRE is identical to the anaerobic response element, AR1c. Data indicate that Upc2 and Ecm22 function through binding to this SRE site. We now show that it is two novel anaerobic AR1b elements in the UPC2 promoter that direct global ERG gene expression in response to a block in de novo ergosterol biosynthesis, brought about by antifungal drug treatment. The AR1b elements are absolutely required for auto-induction of UPC2 gene expression and protein and require Upc2 and Ecm22 for function. We further demonstrate the direct binding of recombinant expressed S. cerevisiae ScUpc2 and pathogenic Candida albicans CaUpc2 and Candida glabrata CgUpc2 to AR1b and SRE/AR1c elements. Recombinant endogenous promoter studies show that the UPC2 anaerobic AR1b elements act in trans to regulate ergosterol gene expression. Our results indicate that Upc2 must occupy UPC2 AR1b elements in order for ERG gene expression induction to take place. Thus, the two UPC2-AR1b elements drive expression of all ERG genes necessary for maintaining normal antifungal susceptibility, as wild type cells lacking these elements have increased susceptibility to azole antifungal drugs. Therefore, targeting these specific sites for antifungal therapy represents a novel approach to treat systemic fungal infections.

In this study, we ask two questions: (1) Is reproductive success independent of parental genetic distance in predominately selfing plants? (2) In the absence of early inbreeding depression, is there substantial maternal and/or paternal variation in reproductive success in natural populations? Seed yield in single pollinations and proportion of seeds sired in mixed pollinations were studied in genetically defined accessions of the predominately selfing plant Arabidopsis thaliana by conducting two diallel crosses. The first diallel was a standard, single pollination design that we used to examine variance in seed yield. The second diallel was a mixed pollination design that utilized a standard pollen competitor to examine variance in proportion of seeds sired. We found no correlation between reproductive success and parental genetic distance, and self-pollen does not systematically differ in reproductive success compared to outcross pollen, suggesting that Arabidopsis populations do not experience embryo lethality due to early-acting inbreeding or outbreeding depression. We used these data to partition the contributions to total phenotypic variation from six sources, including maternal contributions, paternal contributions and parental interactions. For seed yield in single pollinations, maternal effects accounted for the most significant source of variance (16.6 %). For proportion of seeds sired in mixed pollinations, the most significant source of variance was paternal effects (17.9 %). Thus, we show that population-level genetic similarities, including selfing, do not correlate with reproductive success, yet there is still significant paternal variance under competition. This suggests two things. First, since these differences are unlikely due to early-acting inbreeding depression or differential pollen viability, this implicates natural variation in pollen germination and tube growth dynamics. Second, this strongly supports a model of fixation of pollen performance genes in populations, offering a focus for future genetic studies in differential reproductive success.

Background Concerns regarding vaccine safety and pain have prompted certain parents to limit the number of shots their child receives per visit. We estimated the prevalence of shot-limited children in Michigan, described their characteristics, assessed whether shot-limited children were up-to-date on recommended vaccinations, and investigated possible intervention points for vaccination education. Methods We analyzed vaccination registry and birth record data of children born in Michigan during 2012 who had ⩾2 vaccination visits, with ⩾1 visits after age 5 months. Shot-limited was defined as receiving ⩽2 shots at all visits through age 24 months. Nonlimited children received >2 shots at ⩾1 visits. Up-to-date vaccination was based on receipt of a seven-vaccine series and was determined at ages 24 months and 35 months. Risk ratios (RR) were calculated using risk regression. Results Of 101,443 children, a total of 2,967 (3%) children were shot-limited. Mothers of shot-limited children were more likely to be white (RR: 1.2; 95% confidence interval [CI]: 1.2–1.2), college graduate (RR: 1.9; 95% CI: 1.9–2.0), and married (RR: 1.5; 95% CI: 1.5–1.5). Compared with nonlimited children, shot-limited children were more likely to be born in a nonhospital setting (RR: 11.7; 95% CI: 9.4–14.6) and have a midwife attendant (RR: 1.9; 95% CI: 1.7–2.1). Shot-limited children were less likely to be up-to-date on recommended vaccinations (RR: 0.2; 95% CI: 0.2–0.3); this association was stronger for those with a midwife birth attendant (RR: 0.1; 95% CI: 0.1–0.2) rather than a medical doctor (RR: 0.3; 95% CI: 0.2–0.3). Conclusions Shot-limited children are less likely to be up-to-date on vaccinations, possibly leading to increased risk for vaccine-preventable diseases. This association was stronger for those with a midwife birth attendant. This analysis should prompt targeted education, such as to midwives, concerning risks associated with shot-limiting behavior.

This paper presents a body gesture-based controlled mobile robot system, consisting of a DaNI robot, a Kinect sensor, and a Pan-Tilt camera. The Kinect sensor is used to track skeletons and joints of an operator for controlling the robot, while the pan-tilt camera is used to feed back live videos around surrounding information. The DaNI robot platform is a powerful tool for teaching robotics and mechatronics concepts or for developing a robot prototype with LabVIEW Robotics. The body gesture-based controller telepresence controls the DaNI robot by interpreting movements of the two hands of the operator.

In this paper we consider the solution of the compressible Navier–Stokes equations for a class of laminar airfoil flows. The principal objective of this paper is to demonstrate that members of this class of laminar flows have steady-state solutions. These laminar airfoil flow cases are often used to evaluate accuracy, stability and convergence of numerical solution algorithms for the Navier–Stokes equations. In recent years such flows have also been used as test cases for high-order numerical schemes. While generally consistent steady-state solutions have been obtained for these flows using higher order schemes, a number of results have been published with various solutions, including unsteady ones. We demonstrate with two different numerical methods and a range of meshes with a maximum density that exceeds 8 × 10 6 grid points that steady-state solutions are obtained. Furthermore, numerical evidence is presented that even when solving the equations with an unsteady algorithm, one obtains steady-state solutions.

The Hrd1 ubiquitin ligase plays a role in quality control of two substrates associated with the Sec61 translocon., Little is known about quality control of proteins that aberrantly or persistently engage the endoplasmic reticulum (ER)-localized translocon en route to membrane localization or the secretory pathway. Hrd1 and Doa10, the primary ubiquitin ligases that function in ER-associated degradation (ERAD) in yeast, target distinct subsets of misfolded or otherwise abnormal proteins based primarily on degradation signal (degron) location. We report the surprising observation that fusing Deg1, a cytoplasmic degron normally recognized by Doa10, to the Sec62 membrane protein rendered the protein a Hrd1 substrate. Hrd1-dependent degradation occurred when Deg1-Sec62 aberrantly engaged the Sec61 translocon channel and underwent topological rearrangement. Mutations that prevent translocon engagement caused a reversion to Doa10-dependent degradation. Similarly, a variant of apolipoprotein B, a protein known to be cotranslocationally targeted for proteasomal degradation, was also a Hrd1 substrate. Hrd1 therefore likely plays a general role in targeting proteins that persistently associate with and potentially obstruct the translocon.

The numerous surviving formulary volumes compiled by ecclesiastical administrators and lawyers in pre-Reformation England are valuable but neglected adjuncts to the period's surviving church court records. Using material in a fifteenth-century volume originally compiled by a lawyer of the courts at York, this article demonstrates the utility of such volumes to supplement and complement the surviving court books and papers. In particular it draws attention to two cases taken to the Council of Constance. These add to evidence of England's acceptance of that assembly's jurisdictional claims, and illustrate England's integration into the court structures of the broader Catholic Church.

Exine, the outer plant pollen wall, has elaborate species-specific patterns, provides a protective barrier for male gametophytes, and serves as a mediator of strong and species-specific pollen-stigma adhesion. Exine is made of sporopollenin, a material remarkable for its strength, elasticity, and chemical durability. The chemical nature of sporopollenin, as well as the developmental mechanisms that govern its assembly into diverse patterns in different species, are poorly understood. Here, we describe a simple yet effective genetic screen in Arabidopsis (Arabidopsis thaliana) that was undertaken to advance our understanding of sporopollenin synthesis and exine assembly. This screen led to the recovery of mutants with a variety of defects in exine structure, including multiple mutants with novel phenotypes. Fifty-six mutants were selected for further characterization and are reported here. In 14 cases, we have mapped defects to specific genes, including four with previously demonstrated or suggested roles in exine development (MALE STERILITY2, CYP703A2, ANTHER-SPECIFIC PROTEIN6, TETRAKETIDE α-PYRONE REDUCTASE/DIHYDROFLAVONOL-4-REDUCTASE-LIKE1), and a number of genes that have not been implicated in exine production prior to this screen (among them, fatty acid ω-hydroxylase CYP704B1, putative glycosyl transferases At1g27600 and At1g33430, 4-coumarate-coenzyme A ligase 4CL3, polygalacturonase QUARTET3, novel gene At5g58100, and nucleotide-sugar transporter At5g65000). Our study illustrates that morphological screens of pollen can be extremely fruitful in identifying previously unknown exine genes and lays the foundation for biochemical, developmental, and evolutionary studies of exine production.

By the fifteenth century English participation in crusading was mainly a matter of purchasing the confessional letters to gain access to the appropriate indulgence. Information on how such letters were distributed by the pyramid of collectors is scarce. This article draws attention to, and reproduces, injunctions issued by a superior collector to his underlings for the distribution linked to a drive for crusading funds in 1489. The confessional letters were in this case printed, and the injunctions reveal the impact of the new technology, and suggest the greater control of distribution which it permitted.

Sporopollenin is the major component of the outer pollen wall (exine). Fatty acid derivatives and phenolics are thought to be its monomeric building blocks, but the precise structure, biosynthetic route, and genetics of sporopollenin are poorly understood. Based on a phenotypic mutant screen in Arabidopsis (Arabidopsis thaliana), we identified a cytochrome P450, designated CYP704B1, as being essential for exine development. CYP704B1 is expressed in the developing anthers. Mutations in CYP704B1 result in impaired pollen walls that lack a normal exine layer and exhibit a characteristic striped surface, termed zebra phenotype. Heterologous expression of CYP704B1 in yeast cells demonstrated that it catalyzes ω-hydroxylation of long-chain fatty acids, implicating these molecules in sporopollenin synthesis. Recently, an anther-specific cytochrome P450, denoted CYP703A2, that catalyzes in-chain hydroxylation of lauric acid was also shown to be involved in sporopollenin synthesis. This shows that different classes of hydroxylated fatty acids serve as essential compounds for sporopollenin formation. The genetic relationships between CYP704B1, CYP703A2, and another exine gene, MALE STERILITY2, which encodes a fatty acyl reductase, were explored. Mutations in all three genes resulted in pollen with remarkably similar zebra phenotypes, distinct from those of other known exine mutants. The double and triple mutant combinations did not result in the appearance of novel phenotypes or enhancement of single mutant phenotypes. This implies that each of the three genes is required to provide an indispensable subset of fatty acid-derived components within the sporopollenin biosynthesis framework.

Compatible pollinations from many different taxa display nonrandom mating. Here we describe a system for examining questions of nonrandom mating in Arabid- opsis thaliana. Using this system, we demonstrate that Arabidopsis thaliana displays nonrandom mating between distinct accessions. Statistical analysis of these data dem- onstrates aspects of both pollen competition and male- female complementarity in these matings. Cytological experiments implicate pollen germination and pollen tube growth rates as possible causal factors in these nonrandom mating efficiencies.

This paper reports the identification of some fragments of an inscription now preserved in a window at All Saints, North Street, York, as the remnants of a statement of indulgences to reward prayers before a painted image in a window. As far as is known, this is the only surviving glass to demonstrate the proclamation of indulgences in medieval English church windows, although antiquarian evidence of at least one other is recorded.

Jose A Vazquez,1 Anthony C Arnold,2 Robert N Swanson,3 Pinaki Biswas,3 Matteo Bassetti4 1Section of Infectious Diseases, Medical College of Georgia, Georgia Regents University, Augusta, GA, USA; 2UCLA Department of Ophthalmology, Jules Stein Eye Institute, Los Angeles, CA, USA; 3Clinical Research, Global Innovative Pharmaceutical, Pfizer Inc., New York, NY, USA; 4Infectious Diseases Division, Santa Maria della Misericordia University Hospital, Udine, Italy Objective: The objective of this study was to assess the long-term safety of linezolid in patients with chronic infections requiring treatment for ≥6weeks. Enhanced monitoring for optic neuropathy was included to characterize the early development of this side effect and to identify ophthalmologic tests that might be valuable in early detection of this event. Methods: This was a multicenter, open-label, pilot study of patients aged ≥18years on long-term linezolid therapy. Matched control patients were included for baseline assessment comparison. Patients were assessed at study entry, monthly while on treatment, at the end of treatment, and 30days following the last dose. Aggregate ocular safety data were reviewed. Response to treatment was reported. Results: The study was terminated owing to slow enrollment. Twenty-four patients received linezolid; nine patients were included as matched controls. Linezolid was prescribed for a median of 80.5days (range, 50–254days). In patients with a reported clinical outcome, the majority were considered improved or cured. Common treatment-related adverse events (AEs) included anemia, peripheral neuropathy, polyneuropathy, vomiting, and asthenia, and were consistent with the known safety profile. Most AEs resolved or stabilized with discontinuation of treatment. Results of ophthalmologic tests in the one case adjudicated as probable linezolid-associated optic neuropathy revealed abnormal color vision, characteristic changes in the optic disk, and central scotomas in each eye. Conclusion: In our small population, linezolid was generally well tolerated and AEs were consistent with the known safety profile. Extensive ophthalmologic testing of all 24 linezolid-treated patients identified one case adjudicated as probable, linezolid-associated optic neuropathy. Keywords: linezolid, oxazolidinones, optic nerve diseases, peripheral nervous system diseases,safety

Preface List of illustrations Introduction The Starting Point. Part 1: Structures Introduction 1. Brett Edward Whalen The Papacy 2. R.N. Swanson Bishoprics and Parishes 3. R.N. Swanson Manning the Church: Priests and Bishops 4. James D. Mixson Religious Life and Religious Orders Part 2: Forming the Mindset Introduction 5. Ian Christopher Levy The Study of Theology in the Middle Ages 6. Peter D. Clarke Canon Law 7. Cary J. Nederman Social and Political Thought 8. Andrew Reeves Education and Religious Instruction Part 3: Catholicism in Practice Introduction 9. Nicolas Bell Liturgy 10. D. Bornstein Administering the Sacraments 11 Thomas M. Izbicki Sin and Pastoral Care 12 Simon Yarrow Pilgrimage 13 Robert W. Shaffern Death and the Afterlife in the Middle Ages 14 Chistopher Tyerman Violence and Holy War in Western Christendom15 Alixe Bovey 'From Material to Immaterial Things': Gothic Art and Immaterial Culture 16 Alexandra Gajewski Building Christendom: Patrons, Architects and Centres of Innovation in Medieval Europe Part 4: Challenges Introduction 17 Jonathan Elukin Christianity and Judaism Christians and Jews18 Peter Biller Heresy and Dissent 19. Catherine Rider Magic and Superstition Part 5: Shaping a Catholic Society Introduction 20. R.H. Helmholz Jurisdiction and Discipline 21. A.T. Brown Economic Life 22. Kim M. Phillips Gender and Sexuality 23. Alexandra Barratt Literature Afterword Index

A series of prolyl-1-piperazinylacetic acid and prolyl-4-piperidinylacetic acid derivatives were synthesized and evaluated for their activity as VLA-4 antagonists. Of 22 compounds synthesized, 19 compounds showed potent activity with low nanomolar IC50 values. In addition, the representative compounds 11o and 11p with a hydroxy group in the pyrrolidine ring showed moderate plasma clearance in rats (11o, 30 ml/min/kg and 11p, 21 ml/min/kg) and in dogs (11o, 12 ml/min/kg and 11p, 9 ml/min/kg).

At some point in the 1520s the printer Richard Pynson ran off a poster to spread information about an indulgence. The sheet has a poor survival rate: what appears to be the unique extant copy exists as printer’s waste used for book-binding, and is now badly damaged. Nevertheless, the bit which matters for present purposes is almost intact. It notes that Cardinal Wolsey had offered a pardon of ten years and ten Lents to all who recited a specific psalm and set of prayers ‘for the most noble and prosperous estate of our soverayne lorde king Henry the .viii. the quene and the pryncesse’, which could be gained once each day. In addition, all the other bishops of the realm had offered forty days of pardon to everyone who recited five Our Fathers, five Hail Marys, and a Creed for the same intent. (How often that indulgence could be gained is unclear: it may have been secured at each recitation.) The Latin prayers specified to gain Wolsey’s pardon were printed on the bottom half of the sheet, but more than half of that text is now lost.

Plants discriminate among pollen grains that land on the stigma surface, providing compatible pollen with the nutrients and signals required to proceed in pollination, and in many species, recognizing and inhibiting foreign pollen adhesion, hydration, germination and invasion. Much of the stigma machinery involved in these processes remains unknown. It is likely that the expression of a stigma-specific gene program confers specialized structural and functional properties. Here we used microarray technology and cDNA subtraction to build a profile of candidate stigma genes that facilitate early pollination events. Of over 24,000 Arabidopsis genes probed, we identified 11,403 genes expressed in stigma tissue; 317 of these were not expressed in control tissues. Analysis of the stigma transcriptome demonstrated a unique transcriptional profile. Functional specialization of the stigma for extracellular interactions is reflected by an increased number of stigma-specific and stigma-expressed genes involved in sculpturing the cuticle and cell wall, lipid metabolism, as well as genes potentially involved in pollen–stigma interactions.

Indulgences were a vital element in late medieval English religion, but evidence of their attractiveness is limited. Material from the sacrists' rolls of Norwich cathedral priory offers information to cast light on their local appeal, changing over time yet open to manipulation and exploitation. Records of offerings at shrines and images within the cathedral also provide comparative figures to set the scale of indulgence receipts in perspective.