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Although mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is preventable through antiretroviral treatment (ART) during pregnancy and postpartum, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 160,000 new HIV infections occurred among children in 2018 (1). Child survival and HIV-free survival rates* are standard measures of progress toward eliminating MTCT† (2). Nationally representative Population-based HIV Impact Assessment (PHIA)§ survey data, pooled from eight sub-Saharan African countries¶ were used to calculate survival probability among children aged ≤3 years by maternal HIV status during pregnancy and HIV-free survival probability among children aged ≤3 years born to women with HIV infection, stratified by maternal ART** status during pregnancy. Survival probability was significantly lower among children born to women with HIV infection (94.7%) than among those born to women without HIV infection (97.6%). HIV-free survival probability of children born to women with HIV infection differed significantly by the timing of initiation of maternal ART: 93.0% among children whose mothers received ART before pregnancy, 87.8% among those whose mothers initiated ART during pregnancy, and 53.4% among children whose mothers did not receive ART during pregnancy. Focusing on prevention of HIV acquisition and, among women of reproductive age with HIV infection, on early diagnosis of HIV infection and ART initiation when applicable, especially before pregnancy, can improve child survival and HIV-free survival.

Large public-health training events may result in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Universal SARS-CoV-2 testing during trainings for the Uganda Population-based HIV Impact Assessment identified 28 of 475 (5.9%) individuals with coronavirus disease 2019 (COVID-19) among attendees; most (89.3%) were asymptomatic. Until COVID-19 vaccine is readily available for staff and participants, effective COVID-19 mitigation measures, along with SARS-CoV-2 testing, are recommended for in-person trainings, particularly when trainees will have subsequent contact with survey participants.

The American eel (Anguilla rostrata) is an imperilled fish hypothesized to use conspecific cues, in part, to coordinate long-distance migration during their multistage life history. Here, holding water and tissue from multiple American eel life stages was collected and analysed for the presence, profile and concentration of bile acids. Distinct bile acid profiles were identified in glass, elver, yellow eel and silver eel holding waters using ultraperformance liquid chromatography high-resolution mass spectrometry and principal component analysis. Taurochenodeoxycholic acid, taurodeoxycholic acid, cholic acid, deoxycholic acid, taurolithocholic acid and taurocholic acid were detected in whole tissue of American glass eels and elvers, and in liver, intestine and gallbladder samples of late-stage yellow eels. Bile acids were not a major component of silver eel washings or tissue. This study is novel because little was previously known about bile acids produced and emitted into the environment by American eels. Future behavioural studies could evaluate whether any bile acids produced by American eels influence conspecific migratory behaviour.

During recent years, there has been an exponential demand for joint arthroplasty, which has coincided with the global economic recession. In response, the management of patients following arthroplasty is continuously evolving, with the average inpatient length of stay decreasing from weeks to days, and more recently, we have witnessed the development of “outpatient arthroplasty” as a novel concept which aims to address the high volume of patients. The reduction in length of stay has been made possible via implementation of “enhanced recovery programmes” encompassing each stage of the patient journey. Such programmes have aimed to maximise efficiency, whilst maintaining patient satisfaction and achieving exceptional functional outcomes. We have undertaken a thorough review the literature in relation to enhanced recovery programmes (ERPs) and the research that has underpinned individual elements of enhanced recovery. A literature search of enhanced recovery protocols was carried out using PubMed, Cochrane, Embase and OVID. No language restrictions were imposed on the search. ERPs represent a multifactorial framework which may be subdivided into several phases. Pre-operative education programmes, outpatient consultation, pre-anaesthetic assessment, pre-procedural physiotherapy, day-of-surgery admission, pre-operative medications, type of anaesthesia, blood loss reduction protocols, multimodal analgesia delivery, day-of-surgery mobilisation, thromboembolic prophylaxis and ongoing rehabilitation are essential in enhanced recovery. These successful strategies have streamlined the patient pathway of arthroplasty surgery in a cost-effective manner, whilst reducing length of hospital stay and maintaining patient outcomes. Further studies are required to appropriately quantify the impact of individual variables and development of an internationally agreed ERP.

Background/Objectives Urticaria pigmentosa (UP) is the most common form of mastocytosis in children and is associated with systemic signs, symptoms, and triggers. To our knowledge, the effect of UP on children's quality of life has not been studied. The objective of the current study was to characterize the natural history, triggers, and complications of pediatric UP, identify prognostic indicators, and determine its effect on quality of life. Methods Between 2002 and 2007, children with three or more mastocytomas diagnosed by a pediatric dermatologist were recruited during visits at the Children's Hospital of Wisconsin Dermatology Clinic (Milwaukee, WI). Research visits were conducted every 3 years and telephone interviews yearly. The Children's Dermatology Life Quality Index was administered to subjects 4 years of age and older at enrollment. Laboratory test results were collected for subjects younger than 4 years at enrollment. Subjects were followed until UP resolution or study end in August 2015. Results The final cohort size was 43 subjects followed for a median of 8.1 years. Twenty-six subjects were followed through study completion. At age 12 years, 6 patients had disease resolution and 14 remained active. Patients who had disease resolution before age 12 years were more likely to be male and had fewer years of age and smaller lesions, fewer affected areas, and earlier onset. Common medications and anesthetics resulted in no serious reactions. Hymenoptera stings occurred in 51%, with no reports of anaphylaxis. No patient reported a severe effect on quality of life, with most indicating mild to no effect. Conclusion Severe complications are not common with historically identified triggers. Disease does not resolve before adolescence in most children. UP has a minimal effect on quality of life for most children.

Aim: The IMPACT (Improving the Management of Patients with Advanced Colorectal Tumours) initiative was established by the Association of Coloproctology of Great Britain and Ireland in 2017 as a consortium of surgeons (colorectal, hepatobiliary, thoracic), oncologists, radiologists, pathologists, palliative care physicians, patients, carers and charity stakeholders who will work together to improve outcomes in patients with advanced and metastatic colorectal cancer. To establish this initiative, better information is required to establish how further intervention is focused. This paper details the approaches used, and outcomes generated, from a priority setting exercise to inform the design of the IMPACT initiative. Methods: A mixed method approach was employed to set the priorities of patients, clinicians and other key stakeholders in the delivery of optimal care. This consisted of two patient centered consultation events and a questionnaire. Results: A total of 128 participants took part in the consultation exercise; 15 patients, 5 carers/family members, 5 charity representatives and 113 healthcare professionals. Nine key themes for focus were identified, these were: current service provision, specialist services, communication, education, access to care, definitions and standardisation, research and audit, outcome measures, and funding of specialist care. Conclusion: These future priorities will be developed with collaborative engagement in a systematic manner to produce an overall cohesive programme which will deliver a sustainable and efficient clinical and academic service to improving the management of patients with advanced colorectal tumours.

With nearly 1.2 million persons living with HIV and 106,000 new infections, Kenya has one of the highest burdens of HIV infection in the world.1 The most recent Kenya National AIDS Strategic Plan calls for providing coordinated, comprehensive high-quality combination prevention options aimed at controlling the epidemic.2 In recent years, Kenya has expanded prevention efforts which now include increased HIV testing and counseling options, widely available voluntary medical male circumcision, and broader use of antiretroviral treatment to achieve viral suppression and thereby reduce HIV transmission. Also, although prevention strategies have expanded over the past 3 decades of HIV prevention programming, promotion of condom use continues to be a fundamental strategy to reduce the risk of acquiring and transmitting HIV and other sexually transmitted infections (STIs).3 Central to an argument that a condom should be used consistently presumes that it should be used correctly throughout the duration of sex. Any breach of use presents an opportunity for HIV transmission. As such, gathering data on the types and prevalence of incorrect condom use is necessary to determine the need for targeted interventions to improve the effectiveness of condom use. A recent systematic review of 50 published articles of condom use errors found a wide range but generally high percentage of condom users reporting incorrect condom use.4 Common errors and problems included not using condoms throughout intercourse (late application, early removal) and condom breakage, slippage, and leakage.4 Although obtaining precise estimates can be challenging due to different recall periods, framing of questions, and populations studied, the literature indicates that the proportion of individuals who experienced incomplete condom use ranged from 13.6% to 51.1%.5–12 Condom breakage estimates ranged from 0.8% to 40.7%5,6,8–11,13–18 and condom slippage during sex between 13.1% and 19.3%.8–10 Reported condom leakage estimates are 7.6% and 12.5% for men and women, respectively.8,9 It is important to note that the range of estimates reflect varying recall periods, and many of these studies were targeted toward specific groups such as STI clinic attendees, university students, and other high-risk populations. In addition, nearly all were conducted in North America and other areas with concentrated HIV epidemics. None were from Africa. In this present study, we used data from a nationally representative population-based study in Kenya in 2012 to estimate the prevalence and independent predictors of incorrect condom use, and the frequency of selected types of condom errors among sexually active adults and adolescents.

In 2016, an estimated 1.5 million females aged 15-24 years were living with human immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the prevalence of HIV infection among adolescent girls and young women (3.4%) is more than double that for males in the same age range (1.6%) (1). Progress was assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020 targets for adolescent girls and young women in sub-Saharan Africa (90% of those with HIV infection aware of their status, 90% of HIV-infected persons aware of their status on antiretroviral treatment [ART], and 90% of those on treatment virally suppressed [HIV viral load

Introduction Prior reports of Langerhans cell histiocytosis (LCH) suggest that isolated skin involvement is rare and often progresses to systemic disease. More rapid access to pediatric subspecialty care has likely led to more frequent representation of this condition. The purpose of this study is to characterize the natural history of skin-limited LCH in an era of increased access to pediatric subspecialty care. Materials and methods A retrospective chart review was performed on all patients newly diagnosed with LCH between 2001 and 2012 at the Children's Hospital of Wisconsin. Extensive review of laboratory, physical examination, and imaging reports was performed and data collected for patients with biopsy-proven skin LCH. Results Sixteen individuals with skin-limited LCH were identified. The median age at onset of skin eruption was birth (range, birth to 6 mo), and median duration of follow-up was 19.5 months (range, 2 wk to 10 y) from diagnosis. One patient (6%) developed pituitary disease and 1 patient (6%) had refractory skin involvement. All others experienced complete resolution. For patients without progressive or refractory disease, resolution of skin findings occurred within 7 months from onset. Discussion Progression of skin-limited to multisystem LCH likely may be less frequent than previously described.

BACKGROUND In Kenya, it is estimated that there are approximately 3.6 million children aged

BACKGROUND: The Kenyan Ministry of Health initiated a voluntary medical male circumcision (VMMC) program in 2008. We used data from 2 nationally representative surveys to estimate trends in the number demographic characteristics and sexual behaviors of recently circumcised and uncircumcised HIV-uninfected men in Kenya. METHODS: We compared the proportion of circumcised men between the first and second Kenya AIDS Indicator Survey (KAIS 2007 and KAIS 2012) to assess the progress of Kenyas VMMC program. We calculated the number of uncircumcised HIV-uninfected men. We conducted descriptive analyses and used multivariable methods to identify the variables independently associated with HIV-uninfected uncircumcised men aged 15-64 years in the VMMC priority region of Nyanza. RESULTS: The proportion of men who reported being circumcised increased significantly from 85.0% in 2007 to 91.2% in 2012. The proportions of circumcised men increased in all regions with the highest increases of 18.1 and 9.0 percentage points in the VMMC priority regions of Nyanza and Nairobi respectively. Half (52.5%) of HIV-uninfected and uncircumcised men had never been married and 84.6% were not using condoms at all times with their last sexual partner. CONCLUSIONS: VMMC prevalence has increased across Kenya demonstrating the success of the national program. Despite this accomplishment the Nyanza region remains below the target to circumcise 80% of all eligible men aged 15-49 years between 2009 and 2013. As new cohorts of young men enter into adolescence consistent focus is needed. To ensure sustainability of the VMMC program financial resources and coordinated planning must continue.

An inverse correlation between serum 25-hydroxyvitamin D concentration and atopic dermatitis (AD) severity has been suggested.To determine if a statistically significant relationship exists between serum 25-hydroxyvitamin D concentration and AD severity.A cross-sectional study was conducted of patients with AD who were 1 to 18 years of age. An objective Severity Scoring of Atopic Dermatitis (SCORAD) and a serum 25-hydroxyvitamin D concentration were measured for each subject. Statistical analysis was performed using appropriate univariate tests and multivariable models.Ninety-four of 97 enrolled subjects were included in the analysis. Vitamin D deficiency (25-hydroxyvitamin D20 ng/mL) was present in 37 subjects (39%), insufficiency (25-hydroxyvitamin D 21-29 ng/mL) in 33 (35%), and sufficiency (25-hydroxyvitamin D ≥30 ng/mL) in 24 (26%). The correlation between 25-hydroxyvitamin D concentration and SCORAD was not significant (r = -0.001; P = .99). A multivariate model showed that a lower serum 25-hydroxyvitamin D concentration was significantly associated with age 3 years or older (P.0001), black race (P.0001), and winter season (P = .0084).Limitations of this study include the inability to control for natural sunlight exposure, vitamin D intake, and AD treatment; in addition, only a single time point was captured.Serum 25-hydroxyvitamin D concentration is not significantly correlated with AD severity in our pediatric population.

Introduction Home Based Testing and Counselling (HBTC) aims at reaching individuals who have low HIV risk perception and experience barriers which prevent them from seeking HIV testing and counseling (HTC) services. Saturating the community with HTC is needed to achieve the ambitious 90-90-90 targets of knowledge of HIV status, ARV treatment and viral suppression. This paper describes the use of health belief model and community participation principles in HBTC to achieve increased household coverage and HTC uptake. Methods This cross sectional survey was done between August 2009 and April 2011 in Kibera slums, Nairobi city. Using three community participation principles; defining and mobilizing the community, involving the community, overcoming barriers and respect to cultural differences and four constructs of the health belief model; risk perception, perceived severity, perceived benefits of changed behavior and perceived barriers; we offered HTC services to the participants. Descriptive statistics were used to describe socio-demographic characteristics, calculate uptake and HIV prevalence. Results There were 72,577 individuals enumerated at the start of the program; 75,141 residents were found during service delivery. Of those, 71,925 (95.7%) consented to participate, out of which 71,720 (99.7%) took the HIV test. First time testers were (39%). The HIV prevalence was higher (6.4%) among repeat testers than first time testers (4.0%) with more women (7.4%) testing positive than men (3.6%) and an overall 5.5% slum prevalence. Conclusion This methodology demonstrates that the use of community participation principles combined with a psychosocial model achieved high HTC uptake, coverage and diagnosed HIV in individuals who believed they are HIV free. This novel approach provides baseline for measuring HTC coverage in a community.

Some hepatitis C (HCV)-uninfected, high-riskindividuals have HCV-specific cellular immunity without vi-raemia or seroconversion. The characteristics of theseresponses and the risk behavioural associations were stud-ied in 94 subjects in a prospective cohort of recently sero-negative prisoners reporting injecting drug use (IDU).Detailed behavioural data were collected. HCV antibodyand PCR testing were performed. ELISpot assays forHCV-induced interferon (IFN)-c and interleukin (IL)-2production by T lymphocytes, as well as multiplex in vitrocytokine production assays, were performed. Seventy-eightsubjects remained antibody and PCR negative and 16 sero-converted. Of the seronegative group, 22 (28%) had IFN-cELISpot responses in comparison with 13 of the 16 serocon-verters (82%). This seronegative immune status was associ-ated positively with injecting anabolic steroids andnegatively with a recent break from IDU. The IFN-c ELISpotresponses involved both CD4 and CD8 T lymphocytes andwere comparable in magnitude, but narrower in specificity,in uninfected subjects than in seroconverters. A subset ofseronegative subjects had HCV-induced cytokine productionpatterns comparable with the seroconverters with increasedproduction of IFN-c, IL-2 and tumour necrosis factor (TNF)-a and reduced IL-10 in response to nonstructural peptides.In conclusion, comparable patterns of HCV-specific cellularimmunity are found in recently infected subjects and in aminority of high-risk, uninfected subjects. Further charac-terization of these responses and their protective efficacywill inform HCV vaccine development.Keywords: cellular immunity, cytokine, exposed uninfected,hepatitis C virus, injecting drug use, seronegative.

Blastomycosis is a rare fungal infection that most often initially infects the lungs and can progress to disseminated involvement of the skin, bones, and central nervous system (CNS). Pediatric blastomycosis constitutes a small portion of total cases, but delay in diagnosis may result in significant morbidity. Seventeen pediatric cases of blastomycosis were identified at Children’s Hospital of Wisconsin from 1999 to 2009 through retrospective chart review; 53% had evidence of dissemination (bone, skin, or CNS) confirmed by culture. Six cases presented with cutaneous lesions, and five of these were found to have other systemic involvement. These five nonimmunosuppressed cases of primary pulmonary disease with cutaneous involvement plus dissemination to bone or the CNS are reported in detail. The diagnosis of blastomycosis in children is often delayed, and dissemination by the time of diagnosis may be more common than in adults. Cutaneous dissemination may occur in immunocompetent children, may indicate underlying systemic involvement, and can be more readily identified than symptoms of bony or neurologic involvement. These reported cases indicate the importance of dermatologists recognizing and investigating all potentially involved organ systems when a patient presents with characteristic skin lesions with or without a history of respiratory illness.

Context: Adolescent pregnancy, HIV, and other sexually transmitted infections (STIs) are major public health problems in the U.S. Implementing group-based interventions that address the sexual behavior of adolescents may reduce the incidence of pregnancy, HIV, and other STIs in this group. Evidence acquisition: Methods for conducting systematic reviews from the Guide to Community Preventive Services were used to synthesize scientific evidence on the effectiveness of two strategies for group-based behavioral interventions for adolescents: (1) comprehensive risk reduction and (2) abstinence education on preventing pregnancy, HIV, and other STIs. Effectiveness of these interventions was determined by reductions in sexual risk behaviors, pregnancy, HIV, and other STIs and increases in protective sexual behaviors. The literature search identified 6579 citations for comprehensive risk reduction and abstinence education. Of these, 66 studies of comprehensive risk reduction and 23 studies of abstinence education assessed the effects of group-based interventions that address the sexual behavior of adolescents, and were included in the respective reviews. Evidence synthesis: Meta-analyses were conducted for each strategy on the seven key outcomes identified by the coordination team— current sexual activity; frequency of sexual activity; number of sex partners; frequency of unprotected sexual activity; use of protection (condoms and/or hormonal contraception); pregnancy; and STIs. The results of these meta-analyses for comprehensive risk reduction showed favorable effects for all of the outcomes reviewed. For abstinence education, the meta-analysis showed a small number of studies, with inconsistent findings across studies that varied by study design and follow-up time, leading to considerable uncertainty around effect estimates. Conclusions: Based on these findings, group-based comprehensive risk reduction was found to be an effective strategy to reduce adolescent pregnancy, HIV, and STIs. No conclusions could be drawn on the effectiveness of group-based abstinence education.

Alarmingly high HIV prevalence rates among African American men who have sex with men (AAMSM) require the development of effective prevention interventions. In this study of AAMSM conducted in two cities, we explored similarities and differences between HIV-positive and HIV-negative AAMSM on sociodemographic variables, HIV-related risk behaviors, and attitudinal constructs. Differences emerged in several major life areas: (1) poverty, employment, and use of mental health services, (2) sexual risk behaviors, and (3) self-identification with gay identity and culture. With regard to sociodemographic indicators, HIV-positive AAMSM were doing worse than HIV-negative AAMSM in that they were more likely to be disabled, to be living below the poverty level, and accessing mental health services. With regard to risk behaviors and partner characteristics, HIV-positive AAMSM were acting more responsibly than their HIV-negative counterparts, as they were more likely to have used a condom the last time they had sex. In addition, when compared to their HIV-negative counterparts, HIV-positive AAMSM were more likely to have either no casual partners at all or main or casual partners who were HIV-positive, thus preventing new HIV transmission by partnering with other HIV-positive men. Attitudinally, HIV-positive men were more accepting of their sexual attractions to men and were more likely to identify as gay than their HIV-negative peers. Although causality cannot be determined, the findings of this study can be used to strengthen HIV prevention efforts by improving the selection of targeted behaviors and prevention messages for HIV-positive and HIV-negative AAMSM.

Freshwater mussels are one of the most threatened faunas in North America and worldwide, but little research has examined factors leading to successful reproduction (gamete development and fertilization success) in these species. We combined field and laboratory studies to determine the environmental factors influencing successful reproduction in three closely related species of freshwater mussels in a south central U.S. river. Successful gamete development in the field was linked to temperature, specifically the number of accumulated degree days. Laboratory studies confirmed this finding, but also suggested that temperature and food availability interact to regulate gamete development. Our data indicate that successful reproduction may be inhibited by altered temperature regimes found below impoundments.

A community-based intervention, Focus-on-Kids (FOK) has demonstrated risk-behaviour reduction of urban youth. We modified FOK to Focus-on-Teens (FOT) for high schools. High school adolescents ( n = 1190) were enrolled over successive school semesters. The small-group sessions were presented during the school-lunch hours. Confidential surveys were conducted at baseline, immediate, six-, and 12-month postintervention for demographics, parental communication/monitoring, sexual risk behaviours and sexually transmitted diseases (STDs)/HIV/condom-usage knowledge. Sexually active participants were encouraged to volunteer for urine-based STDs testing at the School-Based Health Centres. Many (47.4%) students reported having had sexual intercourse at baseline. Overall behaviours changed towards ‘safer’ sex behaviours (intent-to-use and using condoms, communicating with partner/parents about sex/condoms/STDs) with time ( P < 0.05). Proportion of students with complete correct knowledge of STDs/HIV increased to 88% at time 4 from 80% at baseline after adjusting for age, gender and sexual activity ( P < 0.05). High prevalence of STDs was detected in 875 participants who reported for urine testing at time 1: trichomonas, 11.8%; chlamydia, 10.1% and gonorrhoea, 4.1%. Prevalence decreased significantly for 310 participants who re-tested; chlamydia: 27.4% to 6.1% and gonorrhoea: 11.3% to 3.2%. FOT was successfully implemented as an STDs/HIV risk-reduction intervention. Sustained improvements of knowledge about STDs/HIV/condom usage, decreases in sexual risk behaviours supported the effectiveness of this intervention.

Evidence-based interventions (EBIs) are used in public health to prevent HIV infection among youth and other groups. EBIs include core elements, features that are thought to be responsible for the efficacy of interventions. The authors evaluate experiences of organizations that adopted an HIV-prevention EBI, Focus on Kids (FOK), and their fidelity to the intervention's eight core elements. A cross-sectional telephone survey was administered to 34 staff members from organizations that had previously implemented FOK. Questions assessed how the organization adhered to, adapted, dropped, or altered the intervention. None of the organizations implemented all eight core elements. This study underscores the importance for HIV intervention researchers to clearly identify and describe core elements. More effort is needed to reflect the constraints practitioners face in nonresearch settings. To ensure intervention effectiveness, additional research and technical assistance are needed to help organizations implement HIV prevention EBIs with fidelity.

Summary Ixabepilone (BMS-247550) is a semi-synthetic, microtubule stabilizing epothilone B analogue which is more potent than taxanes and has displayed activity in taxane-resistant patients. The human plasma pharmacokinetics of ixabepilone have been described. However, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. To investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. Due to autoradiolysis, ixabepilone proved to be very unstable when labeled with conventional [14C]-levels (100 μCi in a typical human radio-tracer study). This necessitated the use of much lower levels of [14C]-labeling and an ultra-sensitive detection method, Accelerator Mass Spectrometry (AMS). Eight patients with advanced cancer (3 males, 5 females; median age 54.5 y; performance status 0–2) received an intravenous dose of 70 mg, 80 nCi of [14C]ixabepilone over 3 h. Plasma, urine and faeces were collected up to 7 days after administration and total radioactivity (TRA) was determined using AMS. Ixabepilone in plasma and urine was quantitated using a validated LC-MS/MS method. Mean recovery of ixabepilone-derived radioactivity was 77.3% of dose. Fecal excretion was 52.2% and urinary excretion was 25.1%. Only a minor part of TRA is accounted for by unchanged ixabepilone in both plasma and urine, which indicates that metabolism is a major elimination mechanism for this drug. Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities.

Mycotic aneurysmal disease of the extracranial carotid arteries (ECA) is a rare entity associated with a high morbidity, including rupture, hemorrhage, airway obstruction, and stroke. Surgical management is challenging due to difficult dissection through infected or inflamed tissue. This report highlights a case of ECA-aneurysm infection presenting with stroke and an occluded internal carotid artery, likely due to microbial arteritis on a background of osteomyelitis. Operative intervention was performed to definitively treat the infection and prevent the potential associated complications. In this case, the incident vessel was 100% occluded at presentation, allowing vessel ligation and resection without carotid complex reconstruction.

Summary Background Morphoea is a rare fibrosing disease of the skin and subcutaneous tissue with an unpredictable disease course, running the spectrum from mild skin involvement to severe disfigurement or extracutaneous complications. Objectives Our objective was to describe the natural history of paediatric morphoea and determine patient variables that were associated with severe disease. Patients and methods We conducted a retrospective chart review of patients with morphoea seen in one paediatric hospital system. Information about demographics, clinical characteristics, disease course and treatment were collected. Statistical analysis was performed using appropriate univariate tests and a multivariable model. Results One hundred and fourteen patients met study inclusion criteria. The female : male ratio was 2·6 : 1, and the median age of onset was 7 years old. There were 55 patients (48%) with linear morphoea, 38 patients (33%) with circumscribed morphoea, 12 patients (11%) with generalized morphoea, and nine patients (8%) with mixed morphoea. Neurological symptoms and joint involvement were present in 27 subjects (24%). Extracutaneous manifestations occurred in 38% of subjects with linear morphoea, compared with 15% with generalized morphoea and 3% with circumscribed morphoea (P = 0·0001). Thirty-six per cent of children with disease onset prior to 10 years of age and 5% of children with disease onset after 10 years of age had extracutaneous manifestations (P = 0·0002). Both linear morphoea and early-onset disease were significantly associated with extracutaneous involvement in a multivariable model. Conclusions Children with linear morphoea and disease onset before 10 years of age should be monitored closely for extracutaneous manifestations and need early treatment with systemic medications to prevent disease complications.

Paediatric cutaneous lupus erythematosus (CLE) is uncommon and inadequately described in the literature. Similar to adults, children with CLE develop LE-specific and/or LE-nonspecific skin findings. Similarities and differences in demographics and clinical course between paediatric and adult CLE have not been sufficiently described.To detail the demographic and clinical features of paediatric CLE and compare these findings with those reported in the adult literature.A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE.Patients presented with all five major subtypes of CLE, with some notable differences from adult CLE and previously published reports of paediatric CLE. Progression from discoid LE to systemic LE (SLE) did not occur in our cohort. Patients with subacute CLE were more likely than adults to have lesions below the waist as well as concomitant SLE. Sex distribution for CLE in our study was equal prior to puberty and female predominant in post-pubertal patients.Children with CLE have variable clinical presentations and progression to SLE that may be different from adult disease. Specifically, children with acute and subacute CLE may be more likely than adults to have systemic disease; therefore, patients with these subtypes should be monitored closely for evidence of SLE. Study limitations included small patient numbers that may limit the ability to generalize these data and relatively short follow-up intervals.

We describe the process of adapting a community-level, evidence-based behavioral intervention (EBI), Community PROMISE, for HIV-positive African American men who have sex with men (AAMSM). The Centers for Disease Control and Prevention (CDC) Map of the Adaptation Process (MAP) guided the adaptation process for this new target population by two community-based organizations (CBOs) working in partnership with two research organizations. We describe five steps of the MAP, assessment, selection, preparation, pilot, and implementation, and the use of qualitative interviews, field observations, and a cross-sectional survey. We recommend: (1) development of a centralized interactive website, listserv, or other resources where agencies adapting EBIs can share tools, materials, experiences, lessons learned, and best practices; (2) strengthening Funding Opportunity Announcements by funding incrementally in phases linked to the MAP; and (3) research should examine (a) whether EBIs adapted by CBOs remain efficacious and (b) the best "fit" between the cultural and climate characteristics of effective collaborations between community- and research-based organizations.

The concept of core elements was developed to denote characteristics of an intervention, such as activities or delivery methods, presumed to be responsible for the efficacy of evidence-based behavioral interventions (EBIs) for HIV/AIDS prevention. This paper describes the development of a taxonomy of core elements based on a literature review of theoretical approaches and characteristics of EBIs. Sixty-one categories of core elements were identified from the literature and grouped into three distinct domains: implementation, content and pedagogy. The taxonomy was tested by categorizing core elements from 20 HIV prevention EBIs disseminated by Centers for Disease Control and Prevention. Results indicated that core elements represented all three domains but several were difficult to operationalize due to vague language or the inclusion of numerous activities or constructs. A process is proposed to describe core elements in a method that overcomes some of these challenges. The taxonomy of core elements can be used to identify core elements of EBIs, strengthen the translation of EBIs from research to practice and guide future research seeking to identify essential core elements in prevention interventions.

Background: The objectives of this phase I study were to determine the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of brivanib combined with full-dose cetuximab in patients with advanced gastrointestinal malignancies. Methods: Patients with advanced gastrointestinal malignancies who had failed prior therapies received brivanib (320, 600 or 800 mg daily) plus cetuximab (400 mg m–2 loading dose then 250 mg m–2 weekly). Assessments included adverse events, PK, tumour response, 2[18F]fluoro-2-deoxyglucose positron-emitting tomography and K-Ras mutation analyses. Results: Toxicities observed were manageable; the most common treatment-related toxicities (>10% of patients) were fatigue, diarrhoea, anorexia, increase in aspartate aminotransferase and alanine aminotransferase, acneiform dermatitis, headache, mucosal inflammation, nausea, dry skin, vomiting, hypertension, pruritus, proteinuria and weight loss. Of 62 patients, 6 (9.7%) had objective radiographic partial responses, with an overall response rate of 10%. Median duration of response was 9.2 months; median progression-free survival was 3.9 months. Conclusions: The acceptable toxicity profile and efficacy of brivanib observed in this study were promising. These findings are being further evaluated in a phase III study of brivanib plus cetuximab vs cetuximab alone in patients previously treated with combination chemotherapy for K-Ras wild-type advanced metastatic colorectal cancer.

Background: This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors. Patients and methods: Ninety patients enrolled in this two-part, phase I open-label study of oral brivanib alaninate. The primary objectives of this study were (in part A) dose-limiting toxicity, maximum tolerated dose (MTD) and the lowest biologically active dose level and (in part B) the optimal dose/dose range. The secondary objectives of this study were preliminary evidence of antitumor activity, PK and PD. Results: Across part A (open-label dose escalation and MTD) and part B (open-label dose optimization), 68 patients received brivanib alaninate. Brivanib demonstrated a manageable toxicity profile at doses of 180–800 mg. Most toxic effects were mild. Systemic exposure of the active moiety brivanib increased linearly £1000 mg/day. The MTD was 800 mg/day. Forty-four patients were treated at the MTD: 20 with 800 mg continuously, 11 with 800 mg intermittently and 13 with 400 mg b.i.d. doses. Partial responses were confirmed in two patients receiving brivanib ‡600 mg. Dynamic contrast-enhanced magnetic resonance imaging demonstrated statistically significant decreases in parameters reflecting tumor vascularity and permeability after multiple doses in the 800-mg continuous q.d. and 400-mg b.i.d. dose cohorts. Conclusion: In patients with advanced/metastatic cancer, brivanib demonstrates promising antiangiogenic and antitumor activity and manageable toxicity at doses £800 mg orally q.d., the recommended phase II study dose.

Certain constructs are demonstrated in the research literature to be related to HIV risk behaviors among African American adolescents. This study examines how well these constructs are addressed in evidence-based interventions (EBIs) developed for this population. A literature review on variables for sexual risk behaviors among African American adolescents was undertaken. Simultaneously, a review was conducted of the contents of HIV-prevention EBIs. To facilitate comparison, findings from both were organized into constructs from prominent behavior change theories. Analysis showed that environmental conditions and perceived norms were frequently associated with sexual risk behaviors in the literature, while EBIs devoted considerable time to knowledge, skills, and self-efficacy. Findings imply that (a) EBIs might be complemented with activities that focus on important constructs identified in the literature and (b) researchers should better assess the relationship between skill development and HIV risk behaviors. Implications for practice and research are discussed.

Neonatal lupus erythematosus is an uncommon disease caused by transplacental passage of maternal anti-Ro (SS-A), anti-LA (SS-B), or anti-U1RNP antibodies. Cutaneous findings of neonatal lupus are variable, but annular, erythematous plaques occurring within a few weeks of birth are most typical. Cutaneous lesions of congenital onset lupus erythematosus can differ from that of neonatal lupus erythematosus, presenting with atrophy or scarring, and less commonly, erosions. We report an unusual case of congenital lupus erythematosus presenting at birth with widespread erosions, pancytopenia, and subsequent hepatobiliary disease.

Expert systems continue to evolve for specific applications in medical diagnosis. This is necessary because the influx of new information is so massive that the expert systems must be specialized. The research methodology for this study was based on the usage patterns of expert systems in clinical pathology with data obtained at 94 US medical schools from 202 medical-school-based clinical pathologists. The study showed the link between the use of expert systems in medical schools and within the professional medical community. Initial education in medical schools and ongoing communications through residency programs, post-doctoral fellowships and clinical usage at university hospitals with the goal of technology transfer between medical schools and physicians, seem to represent the future for this valuable diagnostic technique.

We describe an interesting patient with a diffuse smooth muscle hamartoma who presented with hypertrichosis, increased skin folds, and follicular dimpling. While smooth muscle hamartoma classically presents as a small hairy, skin-colored to hyperpigmented patch or plaque, rare presentations with diffuse involvement or follicular papules have been described. We present our patient and review the literature to highlight the diverse and under recognized manifestations of this benign neoplasm.

An epidemic of salmonellosis due to Salmonella enteritidis phage type 4 (PT4), a rise in Campylobacter enteritis, the detection of foodborne transmission in some cases of listeriosis and a large outbreak of botulism in north-west England and Wales were much publicized events in foodborne infectious disease in Britain in 1989. However, other changes took place in the 1980s which attracted less public attention; outbreaks of viral foodborne disease became more common, haemorrhagic colitis was first recorded, yersiniosis and infections caused by Aeromonas spp. increased, cryptosporidiosis and giardiasis came into prominence, and the major foodborne diseases of the past remained rare and usually imported. This article describes the surveillance of foodborne disease and reviews briefly these recent changes with particular reference to England and Wales, under four main headings: increasing foodborne infections, emerging foodborne infections, foodborne intoxications and ‘old’ foodborne diseases, updating a previous review (Galbraith et al., 1987).

A woman with a 5-year history of unilateral orofacial granulomatosis required repeated evaluations (including sequential colonoscopies) to establish the diagnosis of cutaneous Crohn's disease, a condition that proved responsive to low doses of oral methotrexate administered weekly. To our knowledge this is the first report describing the use of methotrexate for treatment of orofacial granulomatosis caused by underlying Crohn's disease.

The utility of surgical resection of solitary metastatic sites in renal cell carcinoma remains controversial. Additionally, the small literature detailing the role of surgical management suggests that patients who have surgical resection of metachronous metastases have a better outcome than those presenting synchronously. We reviewed the medical records of all patients with metastatic renal cell carcinoma who underwent nephrectomy at the University of Iowa Hospitals and Clinics between 1980 and 1993. Patients who had undergone surgical resection of metastatic disease, either at presentation or subsequent to their nephrectomy, were identified. Clinical parameters, time to treatment failure, and survival was evaluated. Eighteen patients underwent surgical resection of metastases, 7 were synchronous to their nephrectomy, and 11 developed metachronous metastases. Resected lesions in both groups included metastases to lung, bone, liver, brain, and soft tissue. The median survival of all patients from time of resection to death or last follow-up was 5.7 years (range, 2 days to 10.7+ years). Two patients remain alive, both with recurrent disease at 5.3 and 10.7 years. Mean time from nephrectomy to death was 2.69 years for the synchronous group and 5.97 years for the metachronous group (p = 0.0599). The role of surgical resection in metastatic renal cell carcinoma remains unproven. The survival of this population is significantly longer than that typical for the disease. In our experience there is no difference in time to treatment failure or survival between synchronous and metachronous resection of metastatic disease.

2530 Background: FDG-PET is used to monitor response in multi-center oncology clinical trials. This study assessed the repeatability of select semi-quantitative standardized uptake values (SUV) as measured by double baseline FDG-PET studies in a multi-center phase I oncology trial. Methods: Double baseline FDG-PET studies were acquired on 62 sequentially enrolled patients. Tumor metabolic activity was assessed by SUVmean, SUVmax, SUVpeak and SUV70%. Compliance with image acquisition guidelines and quality assurance (QA) standards were assessed as to their effect on SUV repeatability. Summary statistics for baseline absolute differences relative to the average of baseline values and repeatability analysis were performed for all patients (full dataset) and a subset with scans that passed QA (QA dataset), analyzed in both a multi-observer (site-reported) and single-observer (central-read) setting. Intra-subject precision of baseline measurements was assessed by repeatability coefficients, intra-subject coefficients of variation, and confidence intervals for all SUV parameters. Results: No statistically significant difference was noted between the two baseline measurements for any of the SUV parameters. Mean baseline differences for SUVmean, SUVmax, SUVpeak and SUV70% were not statistically significant for either dataset, in the multi- or the single-observer setting. The intra-subject coefficient of variation of the SUV parameters ranged from 11–14% (QA dataset) to 16% (full dataset). The 95% repeatability coefficients for individual patient differences, ranged from (-25%, 34%) to (-34%, 52%) for all SUV parameters. Conclusions: Repeatability results of double baseline FDG-PET scans were similar for all SUV parameters assessed in a variety of analysis settings. The variability was acceptable even in the absence of close compliance with current consensus recommendations, supporting the use of FDG-PET imaging as a robust tumor assessment tool in multi-center oncology clinical trials. The results of this study suggest thresholds for determining metabolic response may be on the order of -35%, 50%, allowing increased confidence that a true change from baseline has occurred. [Table: see text]