Search

Background Implementation of evidence-based, resource-appropriate guidelines for breast cancer control should be preceded by a baseline assessment or situational analysis to assess breast health infrastructure, workforce capacity, patient pathways, existing practices, accessibility, and costs. Methods To support the assessment of breast health care systems within the broader context in which they exist, the Breast Health Global Initiative (BHGI) developed, tested, and refined a set of situational analysis tools with which to guide the assessment of breast health care capacity, identify the relative strengths and weaknesses of the health system, and support stakeholders in prioritizing actionable items to advance breast cancer care using evidence-based strategies tailored to their setting. The tools address 6 domains of breast health care delivery: 1) breast cancer early detection practices; 2) breast cancer awareness programs; 3) the availability of breast cancer surgery; 4) the availability of pathology; 5) the availability of radiotherapy, and 6) the availability of systemic therapy services. The current study also describes the more comprehensive International Atomic Energy Agency Programme of Action for Cancer Therapy (PACT) integrated missions for PACT (imPACT) review. Results As of 2020, 5 formal BHGI situational analyses have been performed in India, Brazil, Panama, Tanzania, and Uganda. As of August 2019, a total of 100 imPACT reviews have been conducted in 91 countries. These assessments can contribute to more informed policymaking. Conclusions Situational analyses are a prerequisite for the development of resource-appropriate strategies with which to advance breast cancer control in any setting and should assess services across the entire breast health care continuum as well as the broader structural, sociocultural, personal, and financial contexts within which they operate.

Safety data sheets contain critical information for the safe use, handling, storage, transportation and disposal of chemicals. SDS’s provide essential information for the production of risk assessments. The reliance of such documents by occupational health and safety professionals, chemists, and students is massive. As health and safety professionals it is important to understand that all safety data sheets are not necessarily equal. But how do you know if the information contained on the SDS is accurate? What are the implications/ramifications of having an inaccurate data and information of the SDS? This is paper is a case study surrounding the purchase of a pack of irritant smoke tubes used for the testing of fume cupboards, and the ongoing narrative which occurred when an importing supplier was asked for an Australian GHS Compliant safety data sheet. This presentation also looks at the implications of a poorly written SDS and the possible consequences of an inaccurate information, as well as raising questions about the use of third party SDS and who can be considered as a ‘subject matter expert’.

The question that is posed by this presentation is whether or not risk assessments are a valuable tool or an exercise in futility. Organisations are faced with a conundrum, as WHS/OHS Legislation identifies that employers must ensure the health and safety of people ‘so far as reasonably practicable This is done by identifying the hazard and controlling the risk. But regulators state that the ‘method does not require elaborate systems or large amounts of paper to support it. How the method is put into action depends on the complexity of the hazards or risks, the nature of the organisation and how its business is conducted. What happens if the risk assessment is wrong? Who is qualified to prepare a risk assessment? Assessing risk is not an exact science. It relies on knowledge, experience and an understanding of chemicals, processes and human behaviour. What one person considers as a risk another may not. This presentation also poses the question of whether or not having a poorly prepared risk assessment is better than having no risk assessment. Using case studies this presentation will examine the advantages and disadvantages of proprietary risk assessments along with other issues that are that seemed to have become urban myths when completing risk assessments.

Background: The American College of Radiology (ACR) TI-RADS is a standardized scoring system for thyroid ultrasound reports providing recommendations on the need for fine needle aspirations (FNAs) independent of patient presentation. Aim: The aim of this audit was to determine if the initial presentation of the patient should be considered during the work-up of thyroid nodules. Methods: Data was collected from electronic medical records on 133 patients who underwent thyroid FNAs (165 FNAs in total) and 98 patients who had thyroid surgery for the management of thyroid nodules at Gold Coast University Hospital from Jan 1st 2019 – Dec 31st 2019. Patient presentation, adequacy of the ultrasound report and FNA results were recorded. These results were aligned with final diagnosis after surgery. Results: 98 patients underwent surgery and 29 (29.6%) were found to have malignant nodules, including 12 (12.2%) with microcarcinomas. Of the 29 malignancies, 16 patients presented with a palpable neck lump. Conclusions: Our data suggests a palpable neck lump is a significant factor in determining the risk of malignancy. It may be possible to adjust the current TI-RADS algorithm used to interpret thyroid ultrasounds to include patient presentation. This would reduce unnecessary testing and burden on the healthcare system.

Growing numbers of families now enrol their children in inclusive schools. The purpose of this research was to investigate the perceptions of 44 Australian parents, eight parents had children with ...

According to the Pan American Health Organization, noncommunicable diseases, including cancer, are the leading causes of preventable and premature death in the Americas. Governments and health care systems in Latin America face numerous challenges as a result of increasing morbidity and mortality from cancer. Multiple international organizations have recognized the need for collaborative action on and technical support for cancer research and control in Latin America. The Center for Global Health at the US National Cancer Institute (NCI-CGH) is one entity among many that are working in the region and has sought to develop a strategy for working in Latin America that draws on and expands the collaborative potential of engaged, skilled, and diverse partners. NCI-CGH has worked toward developing and implementing initiatives in collaboration with global partners that share the common objectives of building a global cancer research community and translating research results into evidence-informed policy and practice. Both objectives are complementary and synergistic and are additionally supported by an overarching strategic framework that is focused on partnerships and science diplomacy. This work highlights the overall strategy for NCI-CGH engagement in Latin America through partnerships and diplomacy, and highlights selected collaborative efforts that are aimed at improving cancer outcomes in the region.

Breast cancer is the most common cancer in women worldwide, affecting > 1.6 million women each year, projected to increase to 2.2 million cases annually by 2025. A disproportionate number of the > 500,000 women who die as a result of breast cancer each year reside in low-resource settings. Breast cancer control is an important component of cancer control planning and women’s health programs, and tools are needed across the care continuum to reduce the cancer burden, especially in low-resource settings. Cancer control planning is complex and multifaceted. Evidence shows that outcomes are improved when prevention, early diagnosis, treatment, and palliation are integrated and synchronously developed within a country/region’s health plan. The Knowledge Summaries for Comprehensive Breast Cancer Control are the product of a multiyear collaboration led by the Union for International Cancer Control, Breast Health Global Initiative, Pan American Health Organization, and Center for Global Health of the US National Cancer Institute. Fourteen knowledge summaries distilled from evidence-based, resource-stratified guidelines, and aligned with WHO guidance on breast cancer control, build a framework for resource prioritization pathways and delivery systems for breast cancer control at four levels of available resources: basic, limited, enhanced, and maximal. Each summary contains relevant content to inform breast cancer policy, clinical care, and advocacy, aiding in the development and implementation of policies and programs. These tools provide a common platform for stakeholders, including policymakers, administrators, clinicians, and advocates to engage in decision making appropriate to their local setting. The goal is to facilitate evidence-based policy actions and urgently advance implementation of an integrated approach to reduce breast cancer mortality and improve quality of life.

Summary There is increasing global recognition that national cancer plans are crucial to effectively address the cancer burden and to prioritise and coordinate programmes. We did a global analysis of available national cancer-related health plans using a standardised assessment questionnaire to assess their inclusion of elements that characterise an effective cancer plan and, thereby, improve understanding of the strengths and limitations of existing plans. The results show progress in the development of cancer plans, as well as in the inclusion of stakeholders in plan development, but little evidence of their implementation. Areas of continued unmet need include setting of realistic priorities, specification of programmes for cancer management, allocation of appropriate budgets, monitoring and evaluation of plan implementation, promotion of research, and strengthening of information systems. We found that countries with a non-communicable disease (NCD) plan but no national cancer control plan (NCCP) were less likely than countries with an NCCP and NCP plan or an NCCP only to have comprehensive, coherent, or consistent plans. As countries move towards universal health coverage, greater emphasis is needed on developing NCCPs that are evidence based, financed, and implemented to ensure translation into action.

Solutions to many environmental challenges now require geoscience expertise, knowledge of global interconnectedness, and an understanding of local cultural nuances, a combination for which geoscientists and our students may not be prepared. The Crow Indian Reservation and its borderlands are a microcosm of these challenges, where geoscience expertise must integrate modern science and local worldviews. We propose sense of place education alongside the use of a digital Earth tool in classrooms as a means of (1) engaging American Indian students and teachers in geoscience, (2) using technology to help students apply geoscience expertise to land management issues in their region, and (3) preparing students for an increasingly intercultural and interdisciplinary future. Developed through a collaborative effort among university geoscientists, tribal college faculty, K–8 teachers, and Crow cultural consultants, the Crow Country Digital Globe integrates the local and global, as well as the experiential a...

Incorporating research objectives into national cancer control plans informs effective implementation, and ultimately, health outcomes. We sought to explore the inclusion and description of research priorities in select low- and middle-income countries’ (LMIC) cancer control plans to elucidate gaps and collaborative opportunities. LMIC plans published in English, in 2016 or later, and met World Bank and Human Development Index criteria, comprised the eligible sample. A systematic, inductive approach was used to characterize the research priorities. Two overarching categories of research priorities were identified: Establishing Research Agendas (ERA) and Building Research Capacity (BRC). Codes were subsequently assigned to distinguish between types of research and strategies for developing research capacity. Twelve LMIC cancer control plans were included in the analysis. Six of the 12 plans articulated ERA priorities involving five types of research; the most frequently planned being Health Services Research (31%), followed by Epidemiologic (27%) and Clinical (27%). Five strategies were proposed to build research capacity; the most frequently proposed were “Enhance Cancer Surveillance” (44%) and “Establish Research Infrastructure” (24%). Country-specific variation in ERA and BRC priorities were observed across research type and cancer continuum phase. This is the first systematic examination of research priorities in a subset of LMIC national cancer control plans. Findings suggest that some LMICs intend to focus their research efforts in specific areas and others plan to integrate research across the continuum to enhance cancer control efforts. The extent and overlap of research priorities between countries demonstrates promise for trans-national research collaborations.

Bluetongue virus (BTV) is an arbovirus of the Reoviridae family and causes major economic impact due to the haemorrhagic presentation of Bluetongue disease in ruminants. Target cells of BTV infection are endothelial and immune cells in the mammalian hosts (bovine and ovine) and the midgut and salivary gland cells of the insect host (Culicoides spp.), which is the known vector in the transmission of BTV. Little is known about BTV entry and replication in host derived cells. This thesis investigates the endocytosis mechanisms used by BTV in bovine endothelial (BFA) cells and (KC) cells derived from Culicoides spp. Using a combination of confocal microscopy and flow cytometry, endocytosis pathways were dissected by using pharmacological inhibitors, siRNA and dominant-negative (DN) protein expression which inhibit cellular factors, allowing discrimination between distinct endocytosis pathways. It was found that BTV-1 entry and trafficking to acidic endosomes was relatively slow, consistent with a non-clathrin uptake pathway in BFA cells. During entry, BTV appeared to induce global rearrangements of the actin cytoskeleton and disruption of F-actin filaments with Cytochalasin D inhibited BTV-1 infection by preventing an early step in infection. Furthermore, preliminary evidence suggests that BTV-1 may induce actin rearrangements and uptake by initiating Rho protein signalling. Infection was inhibited by EIPA and IPA-3 which target sodium-proton exchanger 1 and p21 activated kinases respectively, which are cellular factors required for macropinocytosis. Taken together, these results suggest that BTV is utilizing macropinocytosis for entry in BFA cells. Furthermore, expression of DN eps15 and treatment with an inhibitor of CME (Pitstop 2) did not inhibit BTV-1 infection of BFA cells. Interestingly, treatment of KC cells with Pitstop-2 appeared to inhibit BTV-1 infection, indicating that infection may be clathrin dependent in KC cells. Additionally, treatment of BFA and KC cells with Methyl-β-cyclodextrin did not inhibit infection, indicating infection is cholesterol-independent. Treatment of BFA cells with a dynamin inhibitor, Dyngo4a, siRNA targeting dynamin-2 and expression of DN dynamin-2 splice variant ba all inhibited BTV-1 infection and Dyngo4a was shown to inhibit BTV-1 entry. In addition, dynamin inhibitors Dynasore and Dyngo4a also inhibited BTV-1 infection in KC cells. This suggests that the endocytosis pathway used by BTV-1 in BFA and KC cells is dynamin-dependent. This thesis provides evidence that entry of BTV-1 is determined in part by the target cell and uses a dynamin-dependent macropinocytosis-like pathway to enter mammalian cells and CME in insect cells.

Little is known regarding the prevalence of aggression seen during introductions of captive gibbons (Hylobatidae). In this study, an online survey was developed to quantify and collect contextual details regarding the frequency and types of aggression seen during introductions of captive gibbons (Hylobatidae). Nineteen percent of institutions (17 institutions) reported observing aggression, and 6 of these institutions recorded multiple instances of aggression, though a vast majority of these cases resulted in mild injuries or none at all. The female was the primary aggressor in 23% of cases, the male was the primary aggressor in 58% of cases, and both were the primary aggressor in 1 case. Although these aggressive interactions were often not associated with a known cause, 27% of cases were associated with food displacement. In most cases, management changes, including trying new pairings, greatly reduced situational aggression, suggesting that individual personalities may play a factor in aggression. These data begin to explain the extent of aggression observed in captive gibbons; future studies will address possible correlations with aggression and introduction techniques.

This chapter is addressed primarily to potential funders of health research at the national, provincial, and state levels. Health research in general, and cancer research in particular, is not a luxury reserved for high-income countries (HICs); it is a necessity for all countries across the income spectrum. The extent and depth of that research may vary by a country’s financial situation, and the topics may vary by a country’s specific burden of cancers and associated risk factors. Nevertheless, a comprehensive health research plan is foundational to the ability to allocate resources efficiently and effectively, develop human capacity and infrastructure, and identify the appropriate technologies and medicines for health and health services delivery. In short, robust research is essential to building evidence-based cancer prevention and control programs.In recognition of the foundational nature of research, ministers and representatives of ministries of health, science and technology, agriculture, education, foreign affairs, and international cooperation from 53 countries convened in 2008 in Mali at the Bamako Global Ministerial Forum on Research in Health. Of the 53 participating countries, 38 were low- and middle-income countries (LMICs), according to World Bank criteria. The group issued its Call to Action, which articulates the rationale for supporting research to inform public policy, and sent the Call to Action to the World Health Organization (WHO 2008). The Call to Action recommends that national governments allocate at least 2 percent of the budgets of ministries of health to research and that international development agencies invest at least 5 percent of development assistance funds earmarked for the health sector in research. Box 15.1 highlights many of the principles applicable to cancer research.Subsequent white papers and policy statements have made clear the importance of research on noncommunicable diseases and cancer to guide public policy and public investment (See Annotated Select Bibliography).

Tapping into the joy of storytelling and encouraging pupils to write and illustrate their own stories works with even limited vocabulary to boost foreign language learning.

In this prospective cohort study, we have undertaken a comprehensive evaluation of clinical parameters along with variation in 29 genes (including CYP2C9 and VKORC1) to identify factors determining interindividual variability in warfarin response.Consecutive patients (n=311) were followed up prospectively for 26 weeks. Several outcomes chosen to capture both warfarin efficacy and toxicity were assessed. Univariate and multiple regression analyses were undertaken to assess the combined effect of clinical and genetic factors.CYP2C9 was the most important gene determining initial anticoagulant control, whereas VKORC1 was more important for stable anticoagulation. Novel associations with some clinical outcomes were found with single nucleotide polymorphisms in the cytochrome 450 genes CYP2C18 and CYP2C19, which were independent of the associations observed with CYP2C9 and in genes encoding CYP3A5, protein S and clotting factor V, although the variability explained by these genes was small. On the basis of the results of microcosting, adverse events were shown to be a significant predictor of total cost.Accurate prediction of warfarin dose requirement needs to take into account multiple genetic and environmental factors, the contributions of which vary in the induction and maintenance phases of treatment.

BACKGROUND: Infants of human immunodeficiency virus (HIV)-infected women have high mortality, but the immunologic integrity and protection afforded by the breast milk of HIV-infected women is unknown. METHODS: We determined morbidity and mortality by 24 months among breast-fed infants of 588 HIV-infected and 137 HIV-uninfected women followed-up in a clinical trial in Botswana. A matched case-control study compared clinical, behavioral, and breast milk immunologic parameters among 120 HIV-infected women by infant outcome. Breast milk factors were also compared between HIV-infected and HIV-uninfected women. RESULTS: Twenty-four-month mortality was 29.5% among HIV-infected infants, 6.7% among HIV-exposed uninfected infants, and 1.6% among HIV-unexposed infants. No differences were detected in breast milk immunologic profiles of HIV-infected women whose infants were either ill or well. Discontinuation of breast-feeding was the strongest predictor of illness (P

BACKGROUND: A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants. METHODS: We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method. RESULTS: Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P

Single-dose nevirapine given to women and infants reduces mother-to-child HIV transmission but nevirapine resistance develops in a large percentage of women. The objective was to determine whether the maternal nevirapine dose could be eliminated in the setting of zidovudine prophylaxis. A 2 x 2 factorial randomized clinical trial with a double-blinded peripartum factor designed to assess the equivalence of maternal single-dose nevirapine versus placebo with respect to HIV transmission. A total of 709 HIV-infected pregnant women were randomized from four district hospitals in Botswana resulting in 694 live first-born infants. HAART was available for women with AIDS. All women received a background of zidovudine from 34 weeks gestation through delivery and all infants received single-dose nevirapine at birth and zidovudine from birth through 1 month. Women were randomized to receive either single-dose nevirapine or placebo during labor. Main outcome measures: The primary endpoint was infant HIV infection by the 1-month visit. Of the 694 infants in this equivalence study 15 (4.3%) of 345 in the maternal nevirapine arm were HIV infected by 1 month versus 13 (3.7%) of 349 in the maternal placebo arm (95% confidence interval for difference _2.4% to 3.8%) meeting pre-determined equivalence criteria. Nevirapine resistance at 1 month postpartum was detected in 45% of a random sample of women who received nevirapine. In the setting of maternal zidovudine and infant zidovudine plus singledose nevirapine infant HIV infection rates were similar whether women received single-dose nevirapine or placebo. This strategy avoids the potential for maternal nevirapine resistance. (authors)

ExoU is a potent Pseudomonas aeruginosa cytotoxin translocated into host cells by the type III secretion system. A comparison of genomes of various P. aeruginosa strains showed that that the ExoU determinant is found in the same polymorphic region of the chromosome near a tRNA Lys gene, suggesting that exoU is a horizontally acquired virulence determinant. We used yeast recombinational cloning to characterize four distinct ExoU-encoding DNA segments. We then sequenced and annotated three of these four genomic regions. The sequence of the largest DNA segment, named ExoU island A, revealed many plasmid- and genomic island-associated genes, most of which have been conserved across a broad set of β- and γ -Proteobacteria . Comparison of the sequenced ExoU-encoding genomic islands to the corresponding PAO1 tRNA Lys -linked genomic island, the pathogenicity islands of strain PA14, and pKLC102 of clone C strains allowed us to propose a mechanism for the origin and transmission of the ExoU determinant. The evolutionary history very likely involved transposition of the ExoU determinant onto a transmissible plasmid, followed by transfer of the plasmid into different P. aeruginosa strains. The plasmid subsequently integrated into a tRNA Lys gene in the chromosome of each recipient, where it acquired insertion sequences and underwent deletions and rearrangements. We have also applied yeast recombinational cloning to facilitate a targeted mutagenesis of ExoU island A, further demonstrating the utility of the specific features of the yeast capture vector for functional analyses of genes on large horizontally acquired genetic elements.

CD4+ Th1 cells produce IFN-γ, TNF-α, and IL-2. These Th1 cytokines play critical roles in both protective immunity and inflammatory responses. In this study we report that sphingosine kinase 1 (SPHK1), but not SPHK2, is highly expressed in DO11.10 Th1 cells. The expression of SPHK1 in Th1 cells requires TCR signaling and new protein synthesis. SPHK1 phosphorylates sphingosine to form sphingosine-1-phosphate. Sphingosine-1-phosphate plays important roles in inhibition of apoptosis, promotion of cell proliferation, cell migration, calcium mobilization, and activation of ERK1/2. When SPHK1 expression was knocked down by SPHK1 short interfering RNA, the production of IL-2, TNF-α, and IFN-γ by Th1 cells in response to TCR stimulation was enhanced. Consistently, overexpression of dominant-negative SPHK1 increased the production of IL-2, TNF-α, and IFN-γ in Th1 cells. Furthermore, overexpression of SPHK1 in Th1 and Th0 cells decreased the expression of IL-2, TNF-α, and IFN-γ. Several chemokines, including Th2 chemokines CCL17 and CCL22, were up-regulated by SPHK1 short interfering RNA and down-regulated by overexpression of SPHK1. We also showed that Th2 cells themselves express CCL17 and CCL22. Finally, we conclude that SPHK1 negatively regulates the inflammatory responses of Th1 cells by inhibiting the production of proinflammatory cytokines and chemokines.

respectively.) Background. The magnitude of infant antiretroviral (ARV) exposure from breast milk is unknown. Methods. We measured concentrations of nevirapine, lamivudine, and zidovudine in serum and whole breast milk from human immunodeficiency virus type 1 (HIV-1)-infected women in Botswana receiving ARV treatment and serum from their uninfected, breast-feeding infants. Results. Twenty mother-infant pairs were enrolled. Maternal serum concentrations of nevirapine were high (median, 9534 ng/mL at a median of 4 h after nevirapine ingestion). Median breast-milk concentrations of nevirapine, lamivudine, and zidovudine were 0.67, 3.34, and 3.21 times, respectively, those in maternal serum. The median infant serum concentration of nevirapine was 971 ng/mL, at least 40 times the 50% inhibitory concentration and similar to peak concentrations after a single 2-mg/kg dose of nevirapine. The median infant serum concentration of lamivudine was 28 ng/mL, and the median infant serum concentration of zidovudine was 123 ng/mL, but infants were also receiving zidovudine prophylaxis. Conclusions. HIV-1 inhibitory concentrations of nevirapine are achieved in breast-feeding infants of mothers receiving these ARVs, exposing infants to the potential for beneficial and adverse effects of nevirapine ingestion. Further study is needed to understand the impact of maternal ARV treatment on breast-feeding HIV-1 transmission, infant toxicity, and HIV-1 resistance mutations among infected infants.

A single dose of nevirapine for both the mother and newborn infant lowers the rate of mother-to-child transmission of HIV-1 by more than 40%. Nevertheless, large numbers of both women and infants become resistant to nevirapine when exposed to a single peripartum dose. This prospective observational study was done to assess virologic responses to nevirapine-based antiretroviral treatment in women and infants who had previously been randomly assigned to receive a single peripartum dose of nevirapine or placebo. The major end point for both mothers and infants was virologic failure at the 6-month follow-up visit after initiation of antiretroviral therapy. Of 218 women who began antiretroviral therapy, 112 had received a single dose of nevirapine, and 106, placebo. Rates of virologic failure 6 months after the start of antiretroviral treatment were 5% for placebo recipients and 18% for those given a single dose of nevirapine. Among 60 women who began antiretroviral treatment within 6 months of randomization, 42% of those given nevirapine but none of the placebo recipients were virologic failures. In contrast, no significant difference in failure rates were noted in women who began antiretroviral treatment 6 months or more postpartum. Among 30 infants placed on antiretroviral therapy, virologic failure after 6 months was significantly more frequent in those given a single dose of nevirapine than in placebo recipients (P < 0.001). On multivariate analysis stratified according to the timing of initial antiretroviral treatment, baseline counts of CD4 + cells and a single dose of nevirapine, but not the plasma level of HIV-1 RNA, were significantly associated with the time to virologic failure. Where possible, women who qualify for combination antiretroviral treatment on their own account should receive it. They not only are the women at highest risk of AIDS-related complications or death, but also are the likeliest to transmit infection to their infants. For women who do not yet qualify for antiretroviral treatment or where treatment is not available, prophylactic single dose of nevirapine-with or without other antiretroviral agents-remains an important way of preventing mother-to-child transmission of HIV-1 infection. Women exposed more remotely to a single dose of nevirapine have high rates of viral suppression when receiving nevirapine-based antiretroviral therapy.

Though the bulk of research involving photocatalytic oxidation (PCO) of volatile organic compounds (VOCs) has involved the remediation of pollutants at high inlet concentrations, there has been some implication that PCO can be used to reduce exposure to low concentrations of VOCs and improve the quality of indoor air. The high conversion rates previously reported for PCO of VOCs in the parts-per-million (ppm) range may not, however, be applicable to concentrations in the parts-per-billion (ppb) range that are more typical of indoor air quality (IAQ) issues. This paper reports on an examination of the operational characteristics of four PCO reactor designs used for the oxidation of VOCs in the ppb concentration range. Reactor efficiency is examined for three low molecular weight carbonyl compounds commonly associated with IAQ issues: formaldehyde, acetaldehyde, and acetone. The measured response is the destruction of carbonyl reac-tants. Variables include flow stream velocity and reactor residence time. Oxidation of carbonyl compounds is also examined as a function of ultraviolet (UV) radiation intensity. PCO of the formaldehyde and acetone was nearly 100% for all reactor designs. To assist comparison of the reactor designs, oxidation efficiency of trichloroethylene (TCE) was evaluated at inlet concentration in the parts-per-million by volume (ppmv) range.

Preoperative biopsies or imbedded cytological cells will become more and more a primary source of tissue for molecular diagnostic analyses as a result of novel neo-adjuvant treatment regimens for several cancer types. Furthermore there is a growing need to examine metastatic cancer tissue. Hence, nucleic acids need to be reliably isolated and analyzed from small amounts of formalin-fixed and paraffin-embedded (FFPE) tissue. The limited numbers of (tumor) cells in these samples make high quality and sensitive DNA isolation challenging. Also demands for faster turnaround times are growing. Therefore, we evaluated a fully automated DNA/RNA isolation system and compared this with a manual, classical routine molecular pathology method. We compared the quality of the isolates from both tissue cores and micro-dissection for detection of hotspot mutations in KRAS , BRAF applying hydrolysis probe assays. In addition we determined whether the automated method decreases the hands-on-time and turnaround times in routine molecular pathology workflow. In conclusion, the automated method delivers high quality DNA from both small FFPE tissue cores and micro-dissected tissue material. In comparison to classical methods, less than 50% of starting tissue was sufficient as input for micro-dissection. Turnaround times decreased significantly and 50% less hands-on time was needed.

43 A National Cancer Control Plan (NCCP) comprises an important part of a country’s non-communicable disease (NCD) plan and can help countries meet NCD targets outlined in the WHO Global NCD Action Plan. A comprehensive cancer control plan is based on data such as a country’s cancer burden and cancer risk factors, available resources, and local context of culture and health care. The plan provides a systematic framework for implementation of evidence-based and cost-effective strategies for cancer prevention and control. The InternationalCancerControl LeadershipForum isa2-3day regionalworkshopwith thematic seminar modules on cancer control planning and implementation, aswell as interactive action planning sessions. The goal is to increase the capacity of participating countries to initiate or enhance cancer control planning and implementation through a multisectoral approach. The country teams are composed of high-level leaders who represent government agencies, civil society, oncology professionals, and academia. The program approach engages country teams over a year and a half. Approximately 3-6months prior to the forum, teams conduct a situational analysis of the cancer burden and cancer control planning efforts in their country. During the Forum, teams are introduced to evidence-based approaches and exchange best-practices with colleagues to develop a 12-month action plan to move their cancer control planning and implementation efforts forward. In the year after the Forum, country teams and Forum faculty meet for 3-4 follow-upphone calls to address technical assistanceneeds as countries begin to implement their actionplan.Thus far, Forumshavebeenheld inAfrica,SoutheastAsia, thePacific, theCaribbean,Middle East-North Africa, Latin America, and Central Asia regions. The country teams report that the Forum provides an important opportunity to plan with diverse stakeholders. Participants also report increased awareness and knowledge on developing and implementing a national cancer control plan, and learn best-practices from their colleagues in neighboring countries. In some Forums, countries have shown interest to work collaboratively towards regional initiatives. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: No COIs from the authors. Tulika Singh,BrendaKostelecky, and Lisa Stevens, Center forGlobalHealth,National Cancer Institute (NCI),National Institutes of Health, US Department of Health and Human Services Corresponding author: Brenda Kostelecky, Center for Global Health, National Cancer Institute (NCI), National Institutes of Health, US Department of Health and Human Services, 9609 Medical Center Dr, Rockville, MD 20852; 240-276-5585; kosteleckybd@mail.nih.gov DOI: 10.1200/JGO.2016.004853 Tulika Singh Brenda Kostelecky

Inhibition of wound healing by bacteria may result in part from the conversion of plasminogen to plasmin. This conversion results in dissolution of the fibrin seal in a wound or between skin graft and bed. Aprotinin blocks conversion to plasmin, preserving the fibrin clot. The current study was undertaken to determine the effects of high concentrations of bacteria on wound healing and how these effects are mitigated by aprotinin. Dorsal full-thickness skin incisions were made in 40 anesthetized guinea pigs and closed with nylon sutures. Animals were divided into four groups: (1) control wounds, (2) infected wounds, (3) wounds treated with aprotinin, and (4) infected wounds plus aprotinin (single dose). Animals were killed 3 and 4 weeks after the operation. Skin strips containing segments of the healing wounds were pulled apart by a tensiometer until rupture. Stress-strain curves were generated, and wound strength and toughness were determined. All wounds, including those inoculated with bacteria, appeared healed. The 3-week infected group healed with the least strength and toughness (p < 0.001). A single dose of aprotinin administered with the bacterial inoculum reversed this inhibition. In the 4-week groups, the strongest and toughest wounds resulted from bacterial inoculation alone. Aprotinin alone augmented wound healing when compared with controls. These data suggest that wound healing in both clean and infected wounds is augmented when the plasminogen-plasmin pathway is inhibited.

Leukemias are neoplasms that arise from the hematopoetic cells of bone marrow and usually spread first to peripheral blood. Involvement of extramedullary tissue during the course of a leukemia is common and usually does not represent a major diagnostic challenge when the history is available and specimen triage is optimal. In the context of a myeloid origin, extramedullary leukemias are referred to as granulocytic sarcomas, extramedullary myeloid tumors, extramedullary leukemias, or myeloid sarcomas. In the lymphoid category, leukemia involvement of tissue is conventionally distinguished from lymphoma by establishing the presence of 20% or more blasts in the bone marrow. A leukemia with an initial presentation outside the bone marrow mimicking a solid tumor is a rare but well-documented clinical encounter. Diagnostic difficulties may arise, especially when a specimen is not triaged properly due to the clinical presumption of a nonhematopoietic tumor. Systematic handling and proper triaging of biopsies are the keys to reducing diagnostic error and facilitating a timely diagnosis in this category. We report 4 case examples in the pediatric population, presenting in different anatomic sites. The value of fresh specimens and performing touch imprints is discussed and emphasized.

Protein kinase C theta (PKCtheta) is essential for T cell activation, as it is required for the activation of NF-kappaB and expression of IL-2. PKCtheta has also been shown to affect NFAT activation and Th2 differentiation. To better understand the role of PKCtheta in the regulation of T helper cells, we used PKCtheta-deficient DO11.10 transgenic T cells to study its role in vitro. DO11.10 Th1 cells deficient in PKCtheta produced significantly less TNF-alpha and IL-2. The expression of Th2 cytokines, including IL-4, IL-5, IL-10, IL-13 and IL-24 was significantly reduced in PKCtheta-deficient T cells. Moreover, the expression of the Th2 transcription factor, GATA3, was significantly reduced in PKCtheta-deficient T cells. Overexpression of GATA3 by retroviral infection in PKCtheta-deficient T cells resulted in increased expansion of IL-4-producing T cells and higher IL-4 production than that of wild type Th2 cells. IL-5, IL-10, IL-13 and IL-24 expressions were also rescued by GATA3 overexpression. Our observations suggest that PKCtheta regulates Th2 cytokine expression via GATA3.

Background. The ability of highly active antiretroviral therapy (HAART) to reduce human immunodeficiency virus type 1 (HIV-1) RNA and DNA in breast milk has not been described. Methods. We compared breast-milk HIV-1 RNA and DNA loads of women in Botswana who received HAART (nevirapine lamivudine and zidovudine) and women who did not received HAART. Results. Women in the HAART group received treatment for a median of 98 days (range 67-222 days) at the time of breast- milk sampling; 23 (88%) of 26 had whole breast-milk HIV-1 RNA loads

Understanding and assessing the risk posed by oil spills is an essential starting point in oil spill prevention, preparedness, and response. However, it is a complex process and displaying results of a risk analysis can be particularly challenging. By modelling and analysing volumes of oil transported globally over a ten year period from 2001 to 2011, using data obtained from Lloyds' List Intelligence and historical data from ITOPF's tanker spills database, an informative and useful representation of risk can be derived. Incorporation of local marine sensitivity data into the model can further improving the risk assessment process. Although there has been a significant increase in seaborne oil trade over the last thirty years and this is predicted to continue for the foreseeable future, the number of accidental oil spills involving tankers is continuing to decline. GIS tools such as the one we describe are an important part of focusing the on-going efforts of government and industry. These tools can help build awareness of the risks through training courses and seminars and by developing regional initiatives in those areas where they can provide greatest benefit to minimise the threat of future incidents. This poster shows how by using a GIS platform to graphically visualise information, regional areas of heightened vulnerability are more effectively identified and communicated.

With the commercial availability of new high-risk HPV screening assays, we sought to compare a real-time PCR-based assay with our current signal amplification assay. The Cobas 4800 HPV assay (Roche Molecular Diagnostics, Indianapolis, IN) recently received FDA approval for detection of 14 HR-HPV genotypes: HPV-16 and HPV-18 are each identified separately and the other 12 HR-HPV genotypes are identified …

Summary We report here the identification of a virulence-associated factor, Tcf, (tracheal colonization factor), produced by strains of Bordetella pertussis but not Bordetella parapertussis or Bordetella bronchiseptica. This protein is encoded by the tcfA gene. When a strain of B. pertussis 18323 lacking this protein is used to infect mice with an aerosol challenge, the number of bacteria isolated from the tracheas is decreased 10-foid when compared with the parent 18323. The derived amino acid sequence of tcfA predicts a 68 kDa RGD-containing, proline-rich protein, which after cleavage of a typical prokaryotic signal sequence would be 64 kDa. Amino acid sequence analysis demonstrates that the C-terminal 30 kDa of this protein shows 50% identity to the 30 kDa C-terminus of another Bordetella protein, the pertactin precursor. The N-terminal 34 kDa region contains the three amino-acid motif RGD and is 16.5% proline. Coupled in vitro transcription and translation analysis indicates that the tcfA gene product migrates as two bands of approximately 90 kDa. A fusion protein of the N-terminal, 34 kDa portion of Tcf to maltose-binding protein migrates, on SDS–PAGE, 30 kDa higher than expected from the combined molecular weights. Polyclonal antisera raised against the unique N-terminal portion of Tcf recognizes 90 kDa and 60 kDa bands in immunoblots of whole-cell lysates of strains of B. pertussis; it does not recognize any protein in whole-cell lysates of B. bronchiseptica or B. parapertussis. Supernatants of cultures of B. pertussis 18323 contain the 60 kDa form of the protein. Southern blot analysis of chromosomal DNA from strains of B. bronchiseptica and B. parapertussis, using a probe derived from tcfA, shows strong hybridization only to B. pertussis DNA. Thus, Tcf appears to be a unique virulence factor of B. pertussis.