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This paper offers new empirical evidence about the prospects of lower-income, US urban neighbourhoods during the 1990s. Using the Neighborhood Change Database, which offers a balanced panel of census tracts with consistent boundaries from 1970 to 2000 for all metropolitan areas in the US, evidence is found of a significant shift in the fortunes of lower-income, urban neighbourhoods during the 1990s. There was a notable increase in the 1990s in the proportion of lower-income and poor neighbourhoods experiencing a gain in economic status. Secondly, in terms of geographical patterns, it is found that this upgrading occurred throughout the country, not just in selected regions or cities. Finally, it is found that the determinants of changes in lower-income, urban neighbourhoods shifted during the 1990s. In contrast to earlier decades, both the share of Blacks and the poverty rate were positively related to subsequent economic gain in these neighbourhoods during the 1990s.

We recently reported two common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases. We show here that these common European mutations are ancestral variants carried on conserved haplotypes. To facilitate comprehensive analysis of other populations, we report a strategy for full sequencing of this large, highly repetitive gene, and we describe 15 variants, including seven that are prevalent. All the variants are either nonsense or frameshift mutations that, in representative cases, resulted in loss of filaggrin production in the epidermis. In an Irish case-control study, the five most common European mutations showed a strong association with moderate-to-severe childhood eczema (chi2 test: P = 2.12 x 10(-51); Fisher's exact test: heterozygote odds ratio (OR) = 7.44 (95% confidence interval (c.i.) = 4.9-11.3), and homozygote OR = 151 (95% c.i. = 20-1,136)). We found three additional rare null mutations in this case series, suggesting that the genetic architecture of filaggrin-related atopic dermatitis consists of both prevalent and rare risk alleles.

Familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurologic, cutaneous, articular syndrome are related disorders associated with mutations in the CIAS1 gene. They appear to represent a continuum of one disease characterized by IL-1-mediated inflammation. Until recently, these conditions have been difficult to treat; however, with the advent of IL-1-receptor antagonist therapy, many reports of successful treatment of patients with these autoinflammatory diseases have emerged in the past 2 years. We describe an 8-year-old girl, diagnosed with Familial cold auto-inflammatory syndrome, confirmed by presence of a novel CIAS1 mutation, who was refractory to symptomatic treatment. As frequent attacks of urticaria and associated arthralgia had a debilitating effect on the child's lifestyle, a trial of IL-1-receptor antagonist (anakinra) was instituted. Dramatic sustained clinical improvement was evident within days and serum amyloid and C-reactive protein levels normalized within a month. Although several authors have reported successful use of this agent in children with chronic infantile neurologic, cutaneous, articular syndrome, we believe ours is the first report of successful treatment with anakinra in a young child with familial cold auto-inflammatory syndrome.

Atopic dermatitis and psoriasis are the two most common immune-mediated inflammatory disorders affecting the skin. Genome-wide studies demonstrate a high degree of genetic overlap, but these diseases have mutually exclusive clinical phenotypes and opposing immune mechanisms. Despite their prevalence, atopic dermatitis and psoriasis very rarely co-occur within one individual. By utilizing genome-wide association study and ImmunoChip data from >19,000 individuals and methodologies developed from meta-analysis, we have identified opposing risk alleles at shared loci as well as independent disease-specific loci within the epidermal differentiation complex (chromosome 1q21.3), the Th2 locus control region (chromosome 5q31.1), and the major histocompatibility complex (chromosome 6p21-22). We further identified previously unreported pleiotropic alleles with opposing effects on atopic dermatitis and psoriasis risk in PRKRA and ANXA6/TNIP1. In contrast, there was no evidence for shared loci with effects operating in the same direction on both diseases. Our results show that atopic dermatitis and psoriasis have distinct genetic mechanisms with opposing effects in shared pathways influencing epidermal differentiation and immune response. The statistical analysis methods developed in the conduct of this study have produced additional insight from previously published data sets. The approach is likely to be applicable to the investigation of the genetic basis of other complex traits with overlapping and distinct clinical features.

Summary Background Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. Objectives The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. Methods Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. Results The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg−1 per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg−1 vs. 2 mg kg−1 vs. > 2 mg kg−1, the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33–1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04–5·46, P = 0·04, Ptrend < 0·001. Conclusions The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

White-nose syndrome (WNS) is an emerging infectious disease that has resulted in severe declines of its hibernating bat hosts in North America. The ongoing epidemic of white-nose syndrome is a multi-scale phenomenon becau.se it causes hibernaculum-level extirpations, while simultaneously spreading over larger spatial scales. We investigate a neglected topic in ecological epidemiology: how local pathogen-driven extirpations impact large-scale pathogen spread. Previous studies have identified risk factors for propagation of WNS over hibernaculum and landscape scales but none of these have tested the hypothesis that separation of spatial scales and disease-induced mortality at the hibernaculum level might slow or halt its spread. To test this hypothesis, we developed a mechanistic multi-scale model parameterized using white-nose syndrome.county and site incidence data that connects hibernaculum-level susceptible-infectious-removed (SIR) epidemiology to the county-scale contagion process. Our key result is that hibernaculum-level extirpations will not inhibit county-scale spread of WNS. We show that over 80% of counties of the contiguous USA are likely to become infected before the current epidemic is over and that geometry of habitat connectivity is such that host refuges are exceedingly rare. The macroscale spatiotemporal infection pattern that emerges from local SIR epidemiological processes falls within a narrow spectrum of possible outcomes, suggesting that recolonization, rescue effects, and multi-host complexities at local scales are not important to forward propagation of WNS at large spatial scales. If effective control measures are not implemented, precipitous declines in bat populations are likely, particularly in cave-dense regions that constitute the main geographic corridors of the USA, a serious concern for bat conservation.

Results When HR IgE FHS were categorized by eczema severity, those with severe AD were more likely to have HR IgE to cow’s milk (x2 11.3, P < 0.001), egg (x2 6.5, P < 0.05) and peanut (x2 25.4, P < 0.0001) compared to those with mild to moderate AD. Those ≤ 2 years with severe AD were more likely to have multiple HR IgE FHS compared to those with mild to moderate AD for all combinations: cow’s milk and egg (x2 18.62, P < 0.0001); peanut and egg: (x2 24.72, P < 0.0001); cow’s milk and peanut (x2 16.37, P < 0.0001); cow’s milk, egg and peanut (x2 20.01, P < 0.0001).

Summary Background and objectives: This was a prospective audit to assess the incidence and characteristics of early postoperative complications in the recovery room in extubated patients after elective neurosurgical procedures using propofol and remifentanil-based total intravenous anaesthesia. Methods: Vital signs (temperature, conscious level, respiratory rate, oxygen saturation, pulse and blood pressure) and postoperative complications (shivering, nausea, vomiting and cardiorespiratory) were analysed in 145 adult patients over a 1-yr period. Results: The overall shivering, postoperative nausea and vomiting and postoperative hypertension (systolic blood pressure more than 25% of the preoperative value) incidences were 30.3%, 16.6% and 35.2%, respectively. Fifty-one percent of the patients had at least one of the above complications. The complication rates were found to be widely different among various types of neurosurgery. The surgical procedures were divided into five groups: supratentorial craniotomy, posterior fossa craniotomy, intracranial vascular procedures, transphenoidal hypophysectomy and extracranial procedures. Median extubation time was similar in all groups and patients were fully conscious with no hypoxia in the recovery room. The intracranial vascular group had the highest shivering and postoperative nausea and vomiting rates (58.8% and 29.4%, respectively). In the supratentorial craniotomy group, 46% of the patients had hypertension. The overall complication rate (presence of any complications) was highest in the supratentfial craniotomy (55.4%), posterior fossa craniotomy (75%) and intracranial vascular (76.5%) groups. Shivering and overall complication rate was significantly related to the anaesthetic time (P 0.001 and 0.02, respectively). Conclusions: Despite the potential advantages of total intravenous anaesthesia in titratability, rapid return of consciousness and reduced respiratory complications, making it suitable for planned extubation at the end of neurosurgery, the postoperative complications of shivering, postoperative nausea and vomiting and hypertension were still high.

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of approximately 4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.

Purpose. To establish the concurrent validity and time to complete of the Stroke Activity Scale (SAS) a recently developed stroke motor disability scale designed for use in a busy clinical setting.Method. Forty-one stroke patients with residual hemiplegia were recruited and assessed on a single occasion using both the SAS (five items) and modified Motor Assessment Scale (MMAS) (eight items) by a research physiotherapist. Performance was videotaped and assessed subsequently by a second physiotherapist.Results. Pearson's correlation coefficient between the two measures was 0.91. The SAS was significantly quicker to complete than the MMAS (2.8 vs. 10.4 min, p < 0.0001).Conclusion. The SAS had high concurrent validity with the MMAS but was much quicker to complete and therefore more suitable for use in clinical environments where time is at a premium.

This article discusses some of the key differences in board behavior between nonprofit organizations and for-profit firms using a relatively new dataset from New York City nonprofits. We provide evidence on the broader role that nonprofit boards play for their organizations and then give some suggestive results on the relationship between board structure and composition, and individual board member performance. The results provide some evidence that the executive directors of nonprofits may use their power to push boards toward fundraising in place of monitoring activity. Using a fixed-effects framework, we also find no systematic relationship between board personal demographics and performance, although both tenure on a board and multiple board service do seem In the last few years there has been considerable work in the area of governance, focusing principally on the relationship between board composition and the performance of for-profit, publicly traded corporations. In contrast, the empirical economics literature has given little attention to governance among nonprofits, though it is well known that within this sector, governance has a heightened role (see, e.g., Fama and Jensen, 1983; Hansmann, 1980; and Ben-Ner and Van Hoomissen, 1994). This article uses data from a rich new survey on New York City nonprofits to lay out some of the key structural and behavioral differences in the for-profit and nonprofit board, and then provides some preliminary empirical results focusing on the relationship between board structure and individual director characteristics, and specific board behavior.

Ocular toxocariasis in humans is typically a unilateral disease caused by second-stage larvae of the Toxocara species. Serological evidence of widespread infection in humans provides little information on clinical disease. There is only a single previous estimate of the prevalence of ocular toxocariasis (from Alabama). The present survey examined the extent of consultant-diagnosed toxocaral eye disease among a population of schoolchildren. More than 120,000 participants were surveyed by questionnaire and follow-up. Two sets of control subjects from the same school and from the same county were compared with persons who had ocular toxocariasis. The prevalence of consultant-diagnosed toxocaral eye disease was 6.6 cases per 100,000 persons when only cases regarded as definite by the consultant ophthalmologist were included. This increased to 9.7 cases per 100,000 persons when both definite and strongly suspected cases were included. Geophagia and a history of convulsion were associated with toxocaral eye disease in both of the case-control studies. Toxocariasis is a zoonotic disease caused by the infection of humans with second-stage larvae of Toxocara species. Three clinical entities have been recognized in humans: visceral larval migrans, ocular larval migrans, and covert toxocariasis. In children, the seroprevalence of Toxocara infection has been estimated to be 4%– 31% in developed countries and may increase to 86% in tropical regions, where environmental conditions favor the transmission of geohelminths [1].

A timesheet questionnaire was used to assess the time it took from informing the anaesthetist about a case to the start of operative delivery in 78 consecutive patients undergoing caesarean section. Median (IQR [range]) times for grade-1 cases (immediate threat to the life of the mother or fetus) and grade-2 cases (fetal or maternal compromise without immediate threat to life) were 20 (17-35 [6-75]) min and 41 (27-60 [17-136]) min, respectively. Delays occurred in all the component time intervals examined. The primary avoidable delay was the patient's late arrival in theatre. Many significant delays were apparently not perceived by the anaesthetist. In nine (69%) grade-1 cases, the 30-min target decreed by the Association of Anaesthetists of Great Britain & Ireland and the Obstetric Anaesthetists' Association was achieved.

The work reported here is based on the development of a biosensor for the detection of cardiac troponin I, as part of an overall objective of producing a microarray of biosensors for the simultaneous detection of the early and definitive markers of AMI. Initial work on the development of a competitive assay for detection of cTnI did not achieve the required detection limits, despite all formats tested. As a result, it was decided to develop an immunosensor exploiting a sandwich format. As in the case of the myoglobin and H-FABP systems previously reported by us, a one-step sandwich assay was developed, where detector antibody and analyte were added simultaneously to immobilized antibody. Several monoclonal and polyclonal antibody pairs were investigated using sandwich checkerboard assays and the one-step sandwich assay, for the detection of complexed and free cTnI. In the case of complexed cTnI, a linear range of 10–50 ng/mL was obtained, with a detection limit of approximately 5 ng/mL, but a rem...

Background Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. Conclusions HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis. This research was specifically funded by an MRC Population Health Scientist Fellowship awarded to Dr L Paternoster (MR/J012165/1). D.M.E. is supported by an Australian Research Council Future Fellowship (FT130101709) and a Medical Research Council program grant (MC_UU_12013/4)

An amperometric immunosensor for the rapid detection of myoglobin in whole blood was developed. Due to its rapid kinetics, myoglobin is a useful biochemical marker for the early assessment of acute myocardial infarction (AMI). A one-step indirect sandwich assay was employed using a polyclonal goat anti-human cardiac myoglobin antibody with monoclonal mouse anti-myoglobin and goat anti-mouse IgG conjugated to alkaline phosphatase (AP), as the detecting antibodies. The final sensor required 30 min for incubation. The standard curve was linear between 85 and 925 ng/ml. The intra- and inter-assay coefficients of variation were below 8%. No cross-reactivity of the antibodies was found with other cardiac proteins. The overall performance of the sensor, rapid analysis time, wide working range, good precision and specificity demonstrate its potential usefulness for early assessment of AMI.

Government contracting has raised a collection of issues with respect to adequate oversight and accountability. This paper explores one avenue through which contracting agencies may achieve these tasks: through the governance practices of the contractor's board. Oversight and monitoring are a board's key responsibilities, and influencing a board's practices is one way a governmental agency can help to insure quality performance. Agencies could thus use both their selection process and their post-contracting power to influence board practice. Using a new, rich data set on the nonprofit contractors of New York City, a series of hypotheses were tested on the relationship between government funding and board practices. Significant differences were found to exist in board practices as a function of government funding levels, differences that mark a shift of energy away from some activities (i.e., traditional board functions, such as fund-raising) towards others (financial monitoring and advocacy). This suggests that government agencies may indeed use their contracting choices with an eye to particular governance practices. This increased emphasis on such activities appears to crowd out other activities, and is not unambiguously to the benefit of nonprofit board governance. © 2002 by the Association for Public Policy Analysis and Management.

Anthropogenic climate change will present both opportunities and challenges for pool-breeding amphibians. Increased water temperature and accelerated drying may directly affect larval growth, development, and survival, yet the combined effects of these processes on larvae with future climate change remain poorly understood. Increased surface temperatures are projected to warm water and decrease water inputs, leading to earlier and faster wetland drying. So it is often assumed that larvae will experience negative synergistic impacts with combined warming and drying. However, an alternative hypothesis is that warming-induced increases in metabolic rate and aquatic resource availability might compensate for faster drying rates, generating antagonistic larval responses. We conducted a mesocosm experiment to test the individual and interactive effects of pool permanency (permanent vs. temporary) and water temperature (ambient vs. (+) -3 degrees C) on three anurans with fast-to-slow larval development rates (Great Basin spadefoot [Spea intermontana], Pacific chorus frog [Pseudacris regilla], and northern red-legged frog [Rana aurora]). We found that although tadpoles in warmed pools reached metamorphosis 15-17 days earlier, they did so with little cost (2 mm) to size, likely due to greater periphyton growth in warmed pools easing drying-induced resource competition. Warming and drying combined to act antagonistically on early growth (P = 0.06) and survival (P = 0.06), meaning the combined impact was less than the sum of the individual impacts. Warming and drying acted additively on time to and size at metamorphosis. These nonsynergistic impacts may result from cotolerance of larvae to warming and drying, as well as warming helping to offset negative impacts of drying. Our results indicate that combined pool warming and drying may not always be harmful for larval amphibians. However, they also demonstrate that antagonistic responses are difficult to predict, which poses a challenge to proactive conservation and management. Our study highlights the importance of considering the nature of multiple stressor interactions as amphibians are exposed to an increasing number of anthropogenic threats.

The giant cell granuloma of the jaws is a benign osteolytic lesion that may be treated by curettage, intralesional corticosteroids, or calcitonin. These medical treatments may be particularly useful when lesions arise in the immature facial skeleton, recur, or enlarge very rapidly—the last two situations being recognized complications of pregnancy. In this study, a patient is presented with a central giant cell lesion of the maxilla that switched from a relatively indolent growth pattern to become a rapidly enlarging and destructive lesion in the maxilla almost immediately after the patient became pregnant. Although calcitonin treatment is normally avoided in pregnancy, it proved highly effective, caused no obstetric or fetal side effects, and was not contraindicated by renal failure due to lupus nephritis. Histologically, the lesion was converted to a fibro-osseous lesion-like appearance. On the basis of the results of this case, calcitonin appears to be a safe, effective, and conser-vative treatment for giant cell granulomas that enlarge rapidly during pregnancy. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:532-8)

Increasingly, nonprofit, for-profit, and public organizations have been cooperating in producing and distributing a wide range of goods and services. In many cases, the partnerships have arisen from the recognition that different activities are best suited to different governance structures. Yet, working through a cross-sectoral partnership can bring with it complicated managerial issues. This article explores partnering in two important sectors: higher education and welfare reform. In both areas, cooperation across the sectors is widespread and follows lines of comparative advantage. At the same time, there is ample evidence in our cases of classic transactions costs in implementing cross-sectoral partnerships. The article explores ways in which organizations deal with problems of opportunism and imperfect information in contracting across the sectors.

Summary Sweet’s syndrome (SS), a rare reactive neutrophilic dermatosis, has been reported to occur in association with a variety of systemic disorders, categorized by von den Diesch into idiopathic, paraneoplastic, pregnancy and parainflammatory subgroups. The parainflammatory group has been well defined, and includes a wide spectrum of infectious triggers and disorders of immune dysregulation. To date, however, no cases of SS have been described in the context of common variable immunodeficiency (CVID). We report a case of paediatric-onset SS, previously reported as idiopathic, with a subsequent diagnosis of CVID.

Background Tamoxifen has been shown to promote the growth of human endometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifene, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure antiestrogen, are two new antiestrogens being developed for the treatment of breast cancer. The effects of these drugs on endometrial cancer are currently unknown. Our objective was to evaluate the effects of toremifene and ICI 182,780 on the growth of human endometrial cancer in athymic mice. Methods Athymic, ovariectomized mice were implanted with human endometrial tumors and treated with estrogen, tamoxifen, or the new antiestrogens. Results The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometrial tumors in athymic mice were not substantially different. ICI 182,780 inhibited the growth of tamoxifen-stimulated endometrial cancer, in both the presence and the absence of estrogen. Conclusions Toremifene and tamoxifen produce identical effects in our endometrial cancer models. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In contrast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, both in the presence and in the absence of estrogen, suggesting that this drug may be safe with regard to the endometrium, even if it is used following tamoxifen, and that it may not result in an increased incidence of endometrial cancer. Indeed, it is even possible that ICI 182,780 may prove useful as an adjuvant agent in early stage endometrial cancer.

This paper summarizes and synthesizes a series of empirical analyses investigating the role of urban space in affecting minority employment outcomes. It adds to the considerable (but inconclusive) literature by broadening the focus beyond transportation and the “friction of space,” and by expanding the data available for spatial research. The empirical analyses share a common framework linking “access” to youth labor market performance. The first set of results is based on aggregate data relating access to employment outcomes for black youth at the metropolitan level. Access is broadly defined to include traditional measures of geographic distance, as well as measures of social isolation or social access. Metropolitan areas in which the black poor are more spatially isolated are also found to have higher black youth unemployment rates. The second body of evidence relies on the same type of metropolitan measures, combined with individual data on youth living with at least one parent. When individual and family characteristics are controlled for, and white and Hispanic youth are also considered, metropolitan measures of social access exert distinguishable effects upon youth employment -- youth living in urban areas in which they have less residential contact with whites or the non poor are less likely to be employed. The final piece of analysis links the individual records of such youth to tract level measures of access, both social (neighborhood composition variables) and geographic (job access measures). This is accomplished through the creation of a unique data set at the Bureau of the Census. Again, after controlling for individual and family characteristics, the residential conditions of youth affect their employment. Ceteris paribus, youth living in census tracts with fewer employed adults, with fewer whites, and which are further from jobs are less likely to be employed. Results suggest that the overall effects of space on employment outcomes are substantial, explaining between ten and forty percent of the observed racial differences in employment in four urban areas examined. Of this “spatial” effect, the bulk arises from social/informational measures; job access appears to play a much smaller role. However, when measured more precisely, at the census tract level, job access does have a significant effect on youth employment. This effect is less important than other spatial influences. Spatial influences are less important in explaining outcomes than are differences in human capital.

The authors develop a multi-type branching process model of the 2014 Liberian Ebola outbreak that incorporates the impacts of changes in behavior on potential transmission scenarios, thereby informing the path to containment of the epidemic., In 2014, a major epidemic of human Ebola virus disease emerged in West Africa, where human-to-human transmission has now been sustained for greater than 12 months. In the summer of 2014, there was great uncertainty about the answers to several key policy questions concerning the path to containment. What is the relative importance of nosocomial transmission compared with community-acquired infection? How much must hospital capacity increase to provide care for the anticipated patient burden? To which interventions will Ebola transmission be most responsive? What must be done to achieve containment? In recent years, epidemic models have been used to guide public health interventions. But, model-based policy relies on high quality causal understanding of transmission, including the availability of appropriate dynamic transmission models and reliable reporting about the sequence of case incidence for model fitting, which were lacking for this epidemic. To investigate the range of potential transmission scenarios, we developed a multi-type branching process model that incorporates key heterogeneities and time-varying parameters to reflect changing human behavior and deliberate interventions in Liberia. Ensembles of this model were evaluated at a set of parameters that were both epidemiologically plausible and capable of reproducing the observed trajectory. Results of this model suggested that epidemic outcome would depend on both hospital capacity and individual behavior. Simulations suggested that if hospital capacity was not increased, then transmission might outpace the rate of isolation and the ability to provide care for the ill, infectious, and dying. Similarly, the model suggested that containment would require individuals to adopt behaviors that increase the rates of case identification and isolation and secure burial of the deceased. As of mid-October, it was unclear that this epidemic would be contained even by 99% hospitalization at the planned hospital capacity. A new version of the model, updated to reflect information collected during October and November 2014, predicts a significantly more constrained set of possible futures. This model suggests that epidemic outcome still depends very heavily on individual behavior. Particularly, if future patient hospitalization rates return to background levels (estimated to be around 70%), then transmission is predicted to remain just below the critical point around R eff = 1. At the higher hospitalization rate of 85%, this model predicts near complete elimination in March to June, 2015., Author Summary There is considerable uncertainty regarding the steps needed to contain the ongoing Ebola crisis in West Africa, the timeline required to achieve control, and the projected burden of mortality. To address these issues, we develop a branching process model for Ebola transmission that focuses on offspring distributions (i.e., the numbers of new infections caused by each case). We use the model to assess the likely progression of Ebola in Liberia. The model assesses the feedback between new cases and hospital demand under a range of plausible intervention scenarios, particularly ramping-up of treatment facilities over time and increasing the number of individuals seeking hospital treatment through outreach and education. Transmission scenarios—to health care workers in hospitals, to caregivers in the community, to hospital visitors, and to individuals preparing bodies for funerals—are described by distinct offspring distributions based on available data. Results suggest that the outcome of the epidemic depends on both hospital capacity and individual behavior. Additionally, the model highlights the conditions under which transmission might have outpaced hospital capacity, and projects possible epidemic trajectories into 2015.

The use of gene expression profiling has impacted our understanding of breast cancer biology and increasingly has played a role in guiding clinical decisions. We have used hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status for years to guide selection of therapy. More recently, gene expression analysis has facilitated the identification of at least five intrinsic subtypes of breast cancer. Potential therapeutic targets have also been identified using genomic profiling. Several tests, such as the 21-gene recurrence score assay (Oncotype DX) and the 70-gene prognosis signature (MammaPrint), have been well validated as prognostic tools for early-stage breast cancer, and have aided in adjuvant therapy decisions for early-stage, HR-positive breast cancer patients. Genomic profiling has the potential to provide additional insight into drug discovery and clinical trial design by identifying appropriate targeted therapies for subtypes of breast cancer.

Autocrosslinked polysaccharide (ACP) polymers are inter- and intra-molecular esters of hyaluronan (HA) in which part of the carboxyl group is esterified with hydroxyl groups of the same and/or different molecules of the polysaccharides. Suspensions of ACPs in bidistilied water, with relative levels of crosslinking varying from 5% to 20% and different weight concentrations, were obtained to analyse their viscoelastic properties. The steady shear tests showed the pseudoplastic behaviour of ACP, viscosity having a higher value at higher concentrations and degrees of crosslinking. The viscoelastic properties showed an essentially elastic behaviour in the examined frequency range, and they can be modulated by varying both the degree of crosslinking and the weight concentration.

Objective: To determine quality of life in claudicants before and after percutaneous transluminal angioplasty (PTA). Design: Prospective study using EuroQuol questionnaire and visual analogue scales. Setting: District general hospital Materials: Twenty-nine patients undergoing successful PTA. Results: Before PTA patients showed a significantly lower EuroQuol score compared with the normal population. There was also marked impairment of patients usual activities, mobility and perceived health state. Following successful PTA the EuroQuol score, perceived health state, mobility, usual activities, pain and discomfort and mental state were all significantly improved. Conclusions: Intermittent claudication impairs quality of life. Following successful PTA there is significant improvement in symptoms and in general health.

Gentrification touches on issues at the core of the fields of urban economics, planning, and geography. This article aims to look across disciplines and review the literature on gentrification. It begins by discussing how gentrification is defined and understood by different researchers and assessing its importance or prevalence over time. It then contrasts the theoretical approaches used to explain the causes of gentrification in different fields. It focuses on different models used by economists on the one hand and planners, on the other. The economic models of neighborhood change focus more on market forces and individual choices, while planning and geography models emphasize class and politics. Following this, the article reviews the literature on the consequences of gentrification, summarizing the empirical evidence. Finally, it highlights what is still unknown about gentrification, in terms of the process and drivers, its consequences, and the role it might play in future urban revitalization.

A population based case control study was conducted to examine alcohol consumption and maternal smoking during pregnancy and the risk of SIDS in an Irish population. Each SIDS case (n = 287) was compared with control infants (n = 832) matched for date and place of birth for infants born from 1994 to 2001. Conditional logistic regression was used to investigate differences between Cases and Controls establishing Odds Ratio's (OR) and 95% Confidence Intervals (CI). Mothers who smoked were 3 times more likely to have a SIDS Case, and a dose response effect was apparent, with mothers smoking 1-10 cigarettes/day OR 2.93 (CI 1.50-5.71), and those smoking10 cigarettes/day OR 4.36 (CI 2.50-7.61). More Case mothers consumed alcohol during pregnancy than Control mothers and, within drinkers, the amount of alcohol consumed was also greater (p0.05). A dose response with frequency of drinking was apparent. The adjusted odds ratio for those consuming alcohol in all three trimesters was 3.59 (CI:1.40-9.20). Both of these risk factors are modifiable and need to be incorporated into antenatal education from a SIDS point of view.

Seasonality is a complex force in nature that affects multiple processes in wild animal populations. In particular, seasonal variations in demographic processes may considerably affect the persistence of a pathogen in these populations. Furthermore, it has been long observed in computer simulations that under seasonal perturbations, a host–pathogen system can exhibit complex dynamics, including the transition to chaos, as the magnitude of the seasonal perturbation increases. In this paper, we develop a seasonally perturbed Susceptible-Infected-Recovered model of avian influenza in a seabird colony. Numerical simulations of the model give rise to chaotic recurrent epidemics for parameters that reflect the ecology of avian influenza in a seabird population, thereby providing a case study for chaos in a host– pathogen system. We give a computer-assisted exposition of the existence of chaos in the model using methods that are based on the concept of topological hyperbolicity. Our approach elucidates the geometry of the chaos in the phase space of the model, thereby offering a mechanism for the persistence of the infection. Finally, the methods described in this paper may be immediately extended to other infections and hosts, including humans.

Delineating the extent of capillary malformations in the operating suite can be challenging because of a variety of physiologic modifiers, including vasodilatation induced by anesthesia, reactive erythema, and filtering of colors with protective laser eyewear. The use of traditional surgical pens to mark the treatment field has limitations; we have found the use of a white eyeliner pencil to delineate lesions a contemporary technique that assists in identifying the target tissue intraoperatively.

Background: Filaggrin, coded by FLG, is the main source of several major components of natural moisturizing factor (NMF) in the stratum corneum (SC), including pyrrolidone carboxylic acid (PCA) and urocanic acid (UCA). Loss-offunction mutations in FLG lead to reduced levels of filaggrin degradation products in the SC. It has recently been suggested that expression of filaggrin may additionally be influenced by the atopic inflammatory response. In this study, we investigated the levels of several breakdown products of filaggrin in the SC in healthy controls (CTRL) and patients with atopic dermatitis (AD) in relation to FLG null allele status. We examined the relationship between NMF (defined here as the sum of PCA and UCA) and AD severity. Methods: The SC levels of filaggrin degradation products including PCA, UCA, histidine (HIS) and tyrosine were determined in 24 CTRL and 96 patients with moderate-to-severe AD. All subjects were screened for 11 FLG mutations relevant for the study population. Results: The levels of PCA, UCA and HIS correlated with FLG genotype. Furthermore, these levels were higher in the CTRL when compared to AD patients with no FLG mutations. Multiple regression analysis showed that NMF levels were independently associated with FLG genotype and severity of disease. Conclusion: Decreased NMF is a global feature of moderate-to-severe AD; within AD, FLG genotype is the major determinant of NMF, with disease severity as a secondary modifier. NMF components are reliably determined by a noninvasive and relatively inexpensive tape stripping technique.

Potential neighbors often express worries that Housing Choice Voucher holders heighten crime. Yet no research systematically examines the link between the presence of voucher holders in a neighborhood and crime. Our paper aims to do just this, using longitudinal, neighborhood-level crime and voucher utilization data in 10 large U.S. cities. We test whether the presence of additional voucher holders leads to elevated rates of crime, controlling for neighborhood fixed effects, time-varying neighborhood characteristics, and trends in the broader sub-city area in which the neighborhood is located. In brief, crime tends to be higher in census tracts with more voucher households, but that positive relationship becomes insignificant after we control for unobserved differences across census tracts and falls further when we control for trends in the broader area. We find far more evidence for the reverse causal story; voucher use in a neighborhood increases in tracts with rising crime, suggesting that voucher holders tend to move into neighborhoods where crime rates are increasing.

This paper examines empirically the effect of spatially concentrated poverty on minority youth employment and the role of “access” in youth labor markets. A model, in which information about jobs travels through social networks, links labor market outcomes and residential concentration of poverty. The empirical work uses U.S. Census employment data for the largest MSAs, in 1970 and 1980. The key findings are that, although concentration appears to have had no effect on black youth unemployment in 1970, the results for 1980 support “concentration effects” on unemployment for both black and hispanic youth. These effects are sizeable on average, and quite large in some cities.

Since the initial experimental studies in pigs, treatment of vesicoureteral reflux (VUR)inehildrenby endoscopic subureteral injection of polytetrafluoroethylene paste has been used by several investigators with encouraging results. Thirty-seven children (32 girls, 5 boys) with VUR in duplex systems were treated endnscopieally by the senior author (PP) using subureteric Polytef O~ injection and followed up for 1 to 7 years. Thirty-one patients had unilateral refluxing duplex systems and six had bilateraIrefluxing duplex systems. Twenty-sevenrefluxing units had complete ureteral duplication and 16 had incomplete uretesal duplication. All refluxing units had higher grade VUR at least into one of the moieties of the duplex system; 74% of the refluxing duplex ureters having grade 1II VUR and 26% either grade 1V or grade V reflux. Reflux was corrected in 14 (87%) of the 16 ureters with incomplete ureteral duplication after a single injection of Polytet ~ paste and two ureters required two injections to correct VUR. Of the 27 refluxing units with complete ureteral duplication, reflux was corrected in 16 (59%) units after a single injection of Polytef~ paste. 3 (11%) duplex systems showed improvement to grade ] or II reflux after one injection and no further treatment was given. Eight (30%) units with complete ureteral duplication required two to four subureteric injections for the correction of VUR. 93% of refluxing units where reflux was corrected with one subureteric injection of PolytolX~t paste required less than 0.3ml of paste per unit to stop reflux. Thirty-six o f the 37 patients were discharged from the hospital on the day of the procedure. At follow-up micturating cystography 93% of duplex systems continue to show absence of reflux 1 to 7 years after endoscopic correction. There was no evidence of delayed appearance of vesicoureteral obstruction on sonography. No significant complications have been observed in our patients with the use of Teflon to correct reflux. This endoscopic day care procedure offers a simple ahemative in the treatment of refluxing duplex systems.

The complete nucleotide sequence of hyaluronate synthase from Streptococcus sp. and its flanking regions is presented. The gene locus was designated has. Southern-blotting results suggested that the gene was conserved in hyaluronate-producing streptococci. A putative translation-initiation codon was identified and the open reading frame consists of 1566 bp, specifying a protein of 56 kDa. Sequences resembling the promoter and ribosome-binding site of Gram-positive organisms are found upstream of the synthase. The predicted amino-acid sequence reveals the presence of a 35-residue signal peptide. The sequence has some similarity to bacterial peptide-binding proteins.

Atopic dermatitis (AD) is an inflammatory disease characterized by pruritic skin lesions, immunodysregulation, disrupted epidermal barrier function and IgE-mediated sensitization to food and environmental allergens. Identification of the aetiology of AD has become increasingly a priority, as it is clear that the disease burden exceeds AD alone, with many children suffering severe, multi-system and occasionally life-threatening allergic disease. Previous approaches to understanding AD have centred on mechanisms in the adaptive immune system, often with an emphasis on the Th1-Th2 paradigm. Recently, the conceptual focus has increasingly shifted to include a primary defect in the epithelial barrier as a threshold event in moderate-to-severe AD. Familial aggregation of the disease is well established through many family studies of AD, asthma and allergic rhinitis, suggesting a significant heritable component. The identification of loss-of-function mutations in the filaggrin (FLG) gene, whose product is a key structural protein in the outermost layer of the epidermis in up to 50% of patients with AD, provides a significant insight into explaining disease initiation and points to a complex secondary interplay of environmental and immunological sequelae once barrier disruption is established. The elucidation of the environmental, genetic and immunobiological modifiers of this structural molecule may also direct our understanding of the pathomechanisms and endotypes central to the atopic diathesis. The recent identification of a murine model for FLG-AD, with the detection of a homozygous frame-shift mutation in the Flg gene in flaky-tail (ft/ft) mice, stands to rapidly accelerate our understanding of mechanisms and therapeutic intervention points in AD. Refining the molecular understanding of AD and its subtypes will allow for specific diagnostic, treatment and ultimately, preventative algorithms, and has opened an exciting new world of investigative challenges and collaborations.

The ‘flight from blight’ and related literatures on urban population changes and crime have primarily considered times of high or increasing crime rates. Perhaps the most cited recent work in this area, Cullen and Levitt (1999), does not extend through 1990s, a decade during which crime rates declined almost continuously, to levels that were lower than experienced in decades. This paper examines whether such declines contributed to city population growth and retention (abated flight). Through a series of population growth models that attempt to identify causality through several strategies (including instrumental variables) we find at best weak evidence that overall city growth is affected by changes in crime. We find no evidence that growth is differentially sensitive to reductions in crime, as compared to increases. Focusing more narrowly on within MSA migration, residential decisions that are more likely to be sensitive to local conditions, we do find evidence supporting abatement of ‘flight’ – that is, lower levels of crime in central cities in the 1990s are associated with lower levels of migration to the suburbs. This greater ability to retain residents already in the city does not appear to be accompanied by a greater ability to attract new households from the suburbs, or from outside of the metropolitan area.

This paper examines whether the economic gains experienced by low-income neighborhoods in the 1990s followed patterns of classic gentrification (as frequently assumed) — that is, through the in migration of higher income white, households, and out migration (or displacement) of the original lower income, usually minority residents, spurring racial transition in the process. Using the internal Census version of the American Housing Survey, we find no evidence of heightened displacement, even among the most vulnerable, original residents. While the entrance of higher income homeowners was an important source of income gains, so too was the selective exit of lower income homeowners. Original residents also experienced differential gains in income and reported greater increases in their satisfaction with their neighborhood than found in other low-income neighborhoods. Finally, gaining neighborhoods were able to avoid the losses of white households that non-gaining low income tracts experienced, and were thereby more racially stable rather than less.

The aim was to determine the rate of varicella infection and complications in children with disorders of intermediary metabolism (IEM) between the ages of 1 and 16 years attending our national metabolic referral centre. Of 126 children identified, a response was received from 122. A history of previous varicella infection was identified in 64 cases (53%) and of varicella vaccination in 5 (4%). Fifty-three (43%) patients apparently did not have a history of clinical varicella infection. Of the 64 children with a history of varicella infection, five required hospitalisation for complications, including life-threatening lactic acidosis in one patient with mitochondrial disease and metabolic decompensation in four patients. In conclusion, varicella infection may cause an increased risk of metabolic decompensation in patients with IEMs. We propose that a trial of varicella vaccination be considered for this cohort of patients with monitoring of its safety and efficacy.

Tamoxifen (Fig. 1) is the endocrine treatment of choice for all stages of hormone-responsive breast cancer. Additionally tamoxifen has been shown to reduce the incidence of cancer of the opposite breast (1) and has recently been demonstrated to prevent breast cancer (2). Although most women with hormone-responsive advanced breast cancer respond to tamoxifen, their disease eventually becomes refractory to tamoxifen. These patients are known to respond to second-line hormonal therapies. In this chapter, we will focus on new antiestrogens that are currently available or are being developed for use following tamoxifen failure. We have divided these new agents into three groups according to their target-site specificity and molecular properties (3); tamoxifen-like agents, raloxifene-like agents, and pure antiestrogens.